U.S. patent application number 16/308216 was filed with the patent office on 2019-08-29 for system for producing a graft device with a three-dimensional covering.
The applicant listed for this patent is NEOGRAFT TECHNOLOGIES, INC.. Invention is credited to Danielle CZARNOWSKI, Mohammed EL-KURDI, J. Christopher FLAHERTY, Cory LEESON, Matthew MANNARINO, Jon MCGRATH, Kermit SANTIAGO.
Application Number | 20190263068 16/308216 |
Document ID | / |
Family ID | 59093624 |
Filed Date | 2019-08-29 |
United States Patent
Application |
20190263068 |
Kind Code |
A1 |
MANNARINO; Matthew ; et
al. |
August 29, 2019 |
SYSTEM FOR PRODUCING A GRAFT DEVICE WITH A THREE-DIMENSIONAL
COVERING
Abstract
A system for producing a graft device for a patient may
comprise: an imaging device configured to produce image data of a
tubular conduit; and a processing unit configured to receive the
image data from the imaging device. The processing unit may
comprise an algorithm configured to process the image data, and
produce a construction signal based on the image data. A material
delivery device may be configured to receive the construction
signal from the processor, and deliver material to produce a 3D
covering based on the construction signal. The graft device may
comprise the 3D covering positioned about the tubular conduit.
Graft devices and methods of producing graft devices may also be
provided.
Inventors: |
MANNARINO; Matthew;
(Taunton, MA) ; MCGRATH; Jon; (Taunton, MA)
; LEESON; Cory; (Taunton, MA) ; EL-KURDI;
Mohammed; (Taunton, MA) ; CZARNOWSKI; Danielle;
(Taunton, MA) ; SANTIAGO; Kermit; (Taunton,
MA) ; FLAHERTY; J. Christopher; (Taunton,
MA) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
NEOGRAFT TECHNOLOGIES, INC. |
Taunton |
MA |
US |
|
|
Family ID: |
59093624 |
Appl. No.: |
16/308216 |
Filed: |
June 9, 2017 |
PCT Filed: |
June 9, 2017 |
PCT NO: |
PCT/US2017/036800 |
371 Date: |
December 7, 2018 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
62348318 |
Jun 10, 2016 |
|
|
|
Current U.S.
Class: |
1/1 |
Current CPC
Class: |
B33Y 10/00 20141201;
A61M 1/3655 20130101; A61M 27/002 20130101; B29L 2031/7534
20130101; B29C 64/10 20170801; B33Y 80/00 20141201; B29C 64/386
20170801; A61F 2240/002 20130101; A61F 2/06 20130101; B33Y 30/00
20141201; B33Y 50/00 20141201; A61M 2207/10 20130101; A61M 2207/00
20130101 |
International
Class: |
B29C 64/386 20060101
B29C064/386; A61M 27/00 20060101 A61M027/00; A61M 1/36 20060101
A61M001/36; B33Y 50/00 20060101 B33Y050/00; B33Y 80/00 20060101
B33Y080/00; B33Y 30/00 20060101 B33Y030/00; B33Y 10/00 20060101
B33Y010/00 |
Claims
1. System for producing a graft device for a patient comprising: an
imaging device configured to produce image data of a tubular
conduit; and a processing unit configured to receive the image data
from the imaging device and comprising an algorithm, wherein the
algorithm is configured to process the image data and produce a
construction signal based on the image data; a material delivery
device configured to receive the construction signal from the
processing unit, and deliver material to produce a 3-dimensional
(3D) covering based on the construction signal; wherein the graft
device comprises the 3D covering positioned about the tubular
conduit.
2. The system according to any claim herein, wherein the material
delivery device is configured to deliver the 3D covering onto the
tubular conduit.
3. The system according to any claim herein, wherein the 3D
covering is configured to be positioned about the tubular conduit
after being produced by the material delivery device.
4. The system according to any claim herein, wherein the graft
device comprises a coronary artery bypass graft.
5. The system according to any claim herein, wherein the graft
device comprises a dialysis graft.
6. The system according to any claim herein, wherein the graft
device comprises an implant selected from the group consisting of:
artery bypass graft; coronary artery bypass graft; dialysis graft;
peripheral arterial bypass graft; great vessel replacement; great
vessel bypass graft; esophageal graft; tracheal graft; bronchial
graft; biliary duct graft; intestinal graft; organ transplant
vascular connection graft; neuronal replacement implant; ligament
graft; ligament replacement; tendon graft; tendon replacement;
transplant organ coating; fallopian tube; urethra; ureter;
cartilage; hip joint; shoulder joint; intervertebral disc; menisci;
and any combination thereof.
7. The system according to any claim herein, wherein the imaging
device comprises a device selected from the group consisting of:
computerized tomography (CT) imager; optical coherence tomography
(OCT) imager; magnetic resonance imaging (MRI); 3D Scanner; Camera;
Infrared Camera; Ultrasound imager; and any combination
thereof.
8. The system according to any claim herein, wherein the image data
comprises information related to the tubular conduit.
9. The system according to any claim herein, wherein the image data
comprises information related to a portion of the patient's
anatomy.
10. The system according to any claim herein, wherein the image
data comprises data collected when the tubular conduit is
in-situ.
11. The system according to claim 10, wherein the image data
further comprises data collected after the tubular conduit is
harvested from the patient.
12. The system according to any claim herein, wherein the image
data comprises data collected after the tubular conduit is
harvested from the patient.
13. The system according to any claim herein, wherein the image
data comprises data selected from the group consisting of: surface
topography data; surface geometry data; periphery data; length
data; diameter data; thickness data such as wall thickness data;
taper data; eccentricity data; relative position data; trajectory
data; speed of motion data; relative angle data; radiopacity data;
blood flow data; echographic data; spectroscopic data; and any
combination thereof.
14. The system according to any claim herein, wherein the image
data comprises at least one discrete feature of the tubular
conduit.
15. The system according to claim 14, wherein the at least one
discrete feature is identified by the algorithm.
16. The system according to claim 14, wherein the at least one
discrete feature comprises a feature selected from the group
consisting of: sidebranch; recess; projection; end; end portion;
bend portion; lobe; bifurcation; trifurcation; a dilated portion; a
swollen portion; valve; a tapered portion; a location of a surgical
staple; an angled portion; a calcified tissue portion; an
atheromatous tissue portion; a partially occluded portion; a fully
occluded portion; and any combination thereof.
17. The system according to claim 14, wherein the at least one
discrete feature comprises a sidebranch.
18. The system according to claim 17, wherein the image data
comprises sidebranch information selected from the group consisting
of: location; diameter; taper angle; ligation device position;
ligation device geometry; ligation device type; and any combination
thereof.
19. The system according to any claim herein, wherein the image
data comprises information related to a compliance of the tubular
conduit.
20. The system according to any claim herein, wherein the image
data comprises information related to a shape of the tubular
conduit changing over time.
21. The system according to claim 20, wherein the information
related to the shape of the tubular conduit changing over time
comprises information related to the shape of the tubular conduit
changing over time prior to harvesting.
22. The system according to claim 20, wherein the tubular conduit
changes shape due to a change in a parameter selected from the
group consisting of: blood pressure; respiration; patient movement;
and any combination thereof.
23. The system according to any claim herein, wherein the tubular
conduit comprises tissue selected from the group consisting of:
cylindrical tissue; organ tissue; saphenous vein; vein; artery;
urethra; intestine; esophagus; ureter; trachea; bronchi; duct;
fallopian tube; and any combination thereof.
24. The system according to any claim herein, wherein the tubular
conduit comprises tissue selected from the group consisting of:
bone; ligament; tendon; and any combination thereof.
25. The system according to any claim herein, wherein the tubular
conduit comprises artificial material.
26. The system according to any claim herein, wherein the
processing unit comprises memory circuitry.
27. The system according to claim 26, wherein the memory circuitry
is configured to store information selected from the group
consisting of: tissue type; type of the material; information
regarding the application of the graft device; information
regarding use of one or more tools; compliance information; density
information; strength information; modulus of elasticity
information; elastic limit information; wall thickness information;
shrinkage information of the material; cure time information of the
material; spacing to a mandrel and/or other target; minimum bend
radius of the covering; maximum ovality of the covering; and any
combination thereof.
28. The system according to claim 26, wherein the construction
signal is based on information stored in the memory circuitry.
29. The system according to any claim herein, wherein the
processing unit comprises at least one of a microprocessor or a
microcontroller.
30. The system according to any claim herein, wherein the algorithm
is configured to identify at least one discrete feature of the
tubular conduit.
31. The system according to claim 30, wherein the at least one
discrete feature of the tubular conduit identified by the algorithm
comprises a feature selected from the group consisting of:
sidebranch; recess; projection; end; end portion; bend portion;
lobe; bifurcation; trifurcation; a dilated portion; a swollen
portion; valve; a tapered portion; a location of a surgical staple;
an angled portion; a calcified tissue portion; an atheromatous
tissue portion; a partially occluded portion; a fully occluded
portion; and any combination thereof.
32. The system according to claim 30, wherein the 3D covering
comprises at least one customized portion positioned relative to
the at least one discrete feature.
33. The system according to claim 32, wherein the customized
portion is positioned proximate the at least one discrete
feature.
34. The system according to claim 32, wherein the algorithm is
configured to identify at least two discrete features of the
tubular conduit, and wherein the 3D covering comprises at least two
customized portions.
35. The system according to claim 32, wherein the customized
portion comprises a differentiating property selected from the
group consisting of: different thickness; different material;
different porosity; different pore size; different compliance in
one or more directions; different level of conformality; different
texture; different alignment and/or orientation of the deposited
material; different stiffness; different fiber diameter; addition
of a kink-resisting element; addition of an agent; and any
combination thereof.
36. The system according to claim 31, wherein the at least one
discrete feature comprises a protrusion of the tubular conduit.
37. The system according to claim 36, wherein the protrusion
comprises a sidebranch.
38. The system according to claim 36, wherein the 3D covering
comprises a customized portion including a void proximate the
protrusion.
39. The system according to claim 38, wherein the void comprises a
hole.
40. The system according to claim 38, wherein the void comprises a
recess.
41. The system according to claim 36, wherein the at least one
customized portion comprises a portion selected from the group
consisting of: a portion comprising a change in deposition of the
material such as to mechanically reinforce and/or provide a strain
relief at a sidebranch location; a portion configured to constrain
a sidebranch such as to minimize hemodynamic disruption in a lumen
of the tubular conduit; and any combination thereof.
42. The system according to claim 31, wherein the 3D covering
comprises a customized portion including a fillet positioned
proximate the at least one discrete feature.
43. The system according to claim 31, wherein the at least one
discrete feature comprises an end of the tubular conduit.
44. The system according to claim 43, wherein the 3D covering
comprises a customized portion including a taper located proximate
the end of the tubular conduit.
45. The system according to claim 44, wherein the at least one
discrete feature further comprises a second end of the tubular
conduit, and wherein the 3D covering further comprises a second
customized portion including a second tapered positioned proximate
the second end of the tubular conduit.
46. The system according to claim 43, wherein the 3D covering
comprises a customized portion including a reinforced portion
located proximate the end of the tubular conduit.
47. The system according to claim 43, wherein the 3D covering
comprises a customized portion including an optimized anastomosis
portion located proximate the end of the tubular conduit.
48. The system according to claim 47, wherein the optimized
anastomosis portion comprises an optimized shape.
49. The system according to claim 47, wherein the optimized
anastomosis portion comprises an optimized structure.
50. The system according to claim 31, wherein the at least one
discrete feature comprises tissue whose softness is above a
threshold.
51. The system according to claim 50, wherein the customized
portion comprises a differentiating property selected from the
group consisting of: different material; different compliance;
different thickness; different permeability; different porosity;
different anisotropy; and any combination thereof.
52. The system according to claim 31, wherein the at least one
discrete feature comprises tissue whose flexibility is above a
threshold.
53. The system according to claim 52, wherein the customized
portion comprises a differentiating property selected from the
group consisting of: different material; different compliance;
different thickness; different permeability; different porosity;
different anisotropy; and any combination thereof.
54. The system according to claim 31, wherein the at least one
discrete feature comprises tissue whose shape changes over
time.
55. The system according to claim 54, wherein the customized
portion comprises a differentiating property selected from the
group consisting of: different material; different compliance;
different thickness; different permeability; different porosity;
different anisotropy; and any combination thereof.
56. The system according to claim 31, wherein the 3D covering
includes a customized portion including a reinforced portion.
57. The system according to claim 56, wherein the at least one
discrete feature comprises a thin-walled portion of the tubular
conduit, and wherein the customized portion is located proximate
the thin-walled portion.
58. The system according to claim 31, wherein the 3D covering
includes a customized portion including a strain relief.
59. The system according to claim 58, wherein the at least one
discrete feature comprises at least one of an end of the tubular
conduit or a bend portion of the graft device, and wherein the
customized portion is located proximate the at least one discrete
feature.
60. The system according to claim 31, wherein the 3D covering
includes a customized portion including modified porosity.
61. The system according to claim 60, wherein the at least one
discrete feature comprises an anastomosis site and/or a segment of
high curvature of the graft device, and wherein the customized
portion is located proximate the at least one discrete feature.
62. The system according to claim 31, wherein the 3D covering
includes a customized portion including a modified compliance.
63. The system according to claim 62, wherein the modified
compliance comprises a modified radial compliance.
64. The system according to claim 62, wherein the modified
compliance comprises a modified axial compliance.
65. The system according to claim 62, wherein the at least one
discrete feature comprises an anastomosis site, a ligament
attachment site, a tendon attachment site and/or a site of
segmented compliance, and wherein the customized portion is located
proximate the at least one discrete feature.
66. The system according to any claim herein, wherein the algorithm
is configured to create a 3D model of the tubular conduit based on
the image data.
67. The system according to claim 66, wherein 3D model comprises a
spatial model.
68. The system according to claim 66, wherein the algorithm is
further configured to modify the 3D model of the tubular
conduit.
69. The system according to claim 66, wherein the image data
comprises multiple slices of a CT image.
70. The system according to any claim herein, wherein the algorithm
is configured to create a 3D model of a proposed 3D cover.
71. The system according to any claim herein, wherein the algorithm
is configured to create a proposed 3D model of the 3D covering, and
to modify the proposed 3D model to create a final 3D model of the
3D covering.
72. The system according to claim 71, wherein the algorithm is
configured to modify the proposed 3D model based on at least one
discrete feature of the tubular conduit.
73. The system according to claim 71, wherein the algorithm is
configured to modify the proposed 3D model based on user input.
74. The system according to any claim herein, wherein the algorithm
is configured to create a 3D model of at least one of the tubular
conduit or the 3D covering based on boundary conditions.
75. The system according to claim 74, wherein the algorithm is
configured to optimize hemodynamics within the tubular conduit by
performing a function selected from the group consisting of:
reducing flow turbulence; controlling bending radius; controlling
lumen geometry; controlling a transition; controlling a taper;
controlling a bend portion; controlling tortuosity; controlling
wall shear; preventing buckling; optimizing wall shear stress;
modifying an end portion to optimize an anastomotic connection;
reducing geometric mismatch near an anastomotic connection; and any
combination thereof.
76. The system according to any claim herein, wherein the algorithm
is configured to convert information from an imaging coordinate
system to a material deposition coordinate system
77. The system according to claim 76, wherein the imaging
coordinate system comprises Cartesian coordinates and wherein the
material deposition coordinate system comprises a cylindrical,
spherical and/or curvilinear coordinate system.
78. The system according to any claim herein, wherein the material
delivery device comprises at least one nozzle, and wherein the
algorithm is configured to create a pathway of motion for the at
least one nozzle.
79. The system according to claim 78, wherein the algorithm creates
the pathway of motion based on one or more off limits
locations.
80. The system according to claim 78, wherein the pathway of motion
avoids portions of the 3D covering that have already been
created.
81. The system according to claim 78, wherein the pathway of motion
avoids the tubular conduit.
82. The system according to claim 78, wherein the material delivery
device comprises a mandrel, and wherein the pathway of motion
avoids the mandrel.
83. The system according to claim 78, wherein the pathway of motion
minimizes dissipation of heat to the tubular conduit.
84. The system according to claim 83, wherein the pathway of motion
reduces multiple passes of delivery of material in neighboring
regions of the tubular conduit within a time period.
85. The system according to any claim herein, wherein the algorithm
is configured to perform a self-diagnostic.
86. The system according to claim 85, further comprising at least
one sensor configured to produce a signal, wherein the
self-diagnostic is based on the signal from the at least one
sensor.
87. The system according to claim 86, wherein the sensor comprises
one or more sensors selected from the group consisting of: an
optical sensor; a laser; a magnetic sensor; an electrical sensor;
an energy sensor; a pressure sensor; a force sensor; a strain
gauge; a position sensor; a flow sensor; a sound sensor; an
ultrasound sensor; a humidity sensor; and any combination
thereof.
88. The system according to claim 85, wherein the self-diagnostic
is configured to assess a parameter selected from the group
consisting of: electrical connection status; rotational speed;
translational speed; nozzle status; material delivery status;
temperature; chamber environment condition; energy delivered; home
position; a distance between two components of the system; and any
combination thereof.
89. The system according to any claim herein, wherein the algorithm
is configured to create the construction signal based on a property
of the tubular conduit.
90. The system according to claim 89, wherein the construction
signal produces a 3D covering that provides mechanical support to
the tubular conduit.
91. The system according to claim 89, wherein the construction
signal produces a 3D covering with varied properties along a length
of the tubular conduit.
92. The system according to any claim herein, wherein the material
delivery device comprises at least one nozzle.
93. The system according to claim 92, wherein the material delivery
device comprises at least two nozzles.
94. The system according to any claim herein, wherein the material
delivery device comprises a 3D printer.
95. The system according to any claim herein, wherein the material
delivery device is configured to deliver the material using an
additive printing process.
96. The system according to any claim herein, wherein the material
delivery device is configured to deliver the material as a series
of layers.
97. The system according to any claim herein, wherein the material
delivery device comprises a device selected from the group
consisting of: a 3D printer; a layer printing device; an
electrospinning device; a melt-spinning device; a
melt-electrospinning device; a misting assembly; a sprayer; an
electrosprayer; a fused deposition device; a selective laser
sintering device; a fiber dispenser; a wire dispenser; a thread
dispenser; a resin deposition device, such as a UV-curable resin
deposition device; a stereolithography device; a phase separation
device; a wet spinning device; a dip coating device; a lathe; a
milling machine; a chemical etching device; a plasma etching
device; a negative mold-over device; an injection molding device;
and any combination thereof.
98. The system according to claim 97, wherein the material delivery
device comprises two or more devices selected from the group
consisting of: a 3D printer; a layer printing device; an
electrospinning device; a melt-spinning device; a
melt-electrospinning device; a misting assembly; a sprayer; an
electrosprayer; a fused deposition device; a selective laser
sintering device; a fiber dispenser; a wire dispenser; a thread
dispenser; a resin deposition device, such as a UV-curable resin
deposition device; a stereolithography device; a phase separation
device; a wet spinning device; a dip coating device; a lathe; a
milling machine; a chemical etching device; a plasma etching
device; a negative mold-over device; an injection molding device;
and any combination thereof.
99. The system according to any claim herein, wherein the material
comprises one or more materials selected from the group consisting
of: synthetic polymer; natural polymer; protein; metal; metal
alloy; collagen; elastin; a glycosaminoglycan;a proteoglycan; an
alginate; cellulose; gelatin; silk fibroin; fibrinogen; chitosan;
an enzyme; fibronectin; glycerin; integrin; keratin; a vitamin; a
carbohydrate; a monosaccharide; a disaccharide; a polysaccharide; a
nucleoside; abductin; lignin; a glycolipid; a phospholipid; a
sterol; shrilk; cobalt-chrome; nitinol; aluminum oxide; magnesium;
iron; zinc; steel; titanium; vitalium; alacrite; platinum; gold;
silver; copper; manganese; a polyester; a polyurethane; a
polycarbonate; a polyether; a polysulfone; a polyamide; a
polyetheramide; a polystyrene; a polybutadiene; a polyisoprene; a
poly(methyl methacrylate); a polyanhydride; a polydimethylsiloxane;
a polydioxanone; polyethylene; glycol; polyethylene terephthalate;
a polyglycolide; a polyhydroxyalkanoate; polyimide;
polytetrafluoroethylene; polyvinylidene fluoride; polyethylene;
polypropylene; polyvinylfluoride; polyvinylchloride;
polyacylonitrile; silicone; a ceramic; a bioceramic; a bioglass; a
composite material; and any combination thereof.
100. The system according to any claim herein, wherein the 3D
covering comprises varied properties along its length.
101. The system according to claim 100, wherein the 3D covering
comprises at least one customized portion.
102. The system according to any claim herein, wherein the 3D
covering comprises at least a portion with a thickness from about
10 micrometer (.mu.m) to about 1 centimeter (cm).
103. The system according to claim 102, wherein the 3D covering
comprises at least a portion with a thickness from about 50 .mu.m
to about 500 .mu.m.
104. The system according to claim 102, wherein the 3D covering
comprises at least a portion with a thickness from about 200 .mu.m
to about 300 .mu.m.
105. The system according to any claim herein, wherein the 3D
covering comprises at least a portion with a bulk porosity less
than about 99%.
106. The system according to claim 105, wherein the 3D covering
comprises at least a portion with a bulk porosity from about 30% to
about 80%.
107. The system according to claim 105, wherein the 3D covering
comprises at least a portion with a bulk porosity from about 50% to
about 70%.
108. The system according to any claim herein, wherein the 3D
covering comprises a length from about 1 millimeter (mm) to about 1
meter (m).
109. The system according to claim 108, wherein the 3D covering
comprises a length from about 3 centimeter (cm) to about 50 cm.
110. The system according to claim 108, wherein the 3D covering
comprises a length from about 20 cm to about 30 cm.
111. The system according to any claim herein, wherein the 3D
covering comprises at least a portion with a compliance under a
physiologic load that is less than about 99%.
112. The system according to claim 111, wherein the 3D covering
comprises at least a portion with a compliance under a physiologic
load that is from about 1% to about 50%.
113. The system according to claim 111, wherein the 3D covering
comprises at least a portion with a compliance under a physiologic
load that is from about 10% to about 25%.
114. The system according to any claim herein, wherein the 3D
covering comprises at least a portion with an ultimate strength
from about 0.1 Megapascal (MPa) to about 500 MPa.
115. The system according to claim 114, wherein the 3D covering
comprises at least a portion with an ultimate strength from about
0.5 MPa to about 100 MPa.
116. The system according to claim 114, wherein the 3D covering
comprises at least a portion with an ultimate strength from about 1
MPa to about 10 MPa.
117. The system according to any claim herein, wherein the 3D
covering comprises at least a portion with a biodurability from
about 1 hour to about 10 years.
118. The system according to claim 117, wherein the 3D covering
comprises at least a portion with a biodurability from about 48
hours to about 2 years.
119. The system according to claim 117, wherein the 3D covering
comprises at least a portion with a biodurability from about 3
months to about 6 months.
120. The system according to any claim herein, wherein the 3D
covering comprises a drug, and wherein the 3D covering is
configured to release the drug for a duration from about 1 hour to
about 10 years.
121. The system according to claim 120, wherein the 3D covering is
configured to release the drug for a duration from about 48 hours
to about 2 years.
122. The system according to claim 120, wherein the 3D covering is
configured to release the drug for a duration from about 3 months
to about 6 months.
123. The system according to any claim herein, wherein the 3D
covering comprises at least a portion with a macropore size from
about 10 .mu.m to about 1000 .mu.m.
124. The system according to claim 123, wherein the 3D covering
comprises at least a portion with a macropore size from about 20
.mu.m to about 200 .mu.m.
125. The system according to claim 123, wherein the 3D covering
comprises at least a portion with a macropore size from about 50
.mu.m to about 100 .mu.m.
126. The system according to any claim herein, wherein the 3D
covering comprises at least a portion with a macropore spacing from
about 10 .mu.m to about 1000 .mu.m.
127. The system according to claim 126, wherein the 3D covering
comprises at least a portion with a macropore spacing from about
100 .mu.m to about 500 .mu.m.
128. The system according to claim 126, wherein the 3D covering
comprises at least a portion with a macropore spacing from about
200 .mu.m to about 400 .mu.m.
129. The system according to any claim herein, wherein the 3D
covering comprises at least a portion with a water permeability of
less than about 300 milliliter per centimeter squared per minute
(ml/cm.sup.2/min).
130. The system according to claim 129, wherein the 3D covering
comprises at least a portion with a water permeability from about
50 ml/cm.sup.2/min to about 200 ml/cm.sup.2/min.
131. The system according to claim 129, wherein the 3D covering
comprises at least a portion with a water permeability from about
100 ml/cm.sup.2/min to about 150 ml/cm.sup.2/min.
132. The system according to any claim herein, wherein the 3D
covering comprises a texture with from about 0.25 nanometer (nm) to
about 50 .mu.m roughness value Ra.
133. The system according to claim 132, wherein the 3D covering
comprises a texture with from about 0.2 .mu.m to about 12.5 .mu.m
roughness value Ra.
134. The system according to claim 132, wherein the 3D covering
comprises a texture with from about 1.6 .mu.m to about 6.3 .mu.m
roughness value Ra.
135. The system according to any claim herein, wherein the 3D
covering comprises a suture retention strength up to about 1
kilogram-force (Kgf).
136. The system according to claim 135, wherein the 3D covering
comprises a suture retention strength of from about 50 gram-force
(gf) to about 500 gf.
137. The system according to claim 135, wherein the 3D covering
comprises a suture retention strength of from about 100 gf to about
200 gf.
138. The system according to any claim herein, wherein the 3D
covering comprises at least a portion with a kink radius of up to
about 1 meter (m).
139. The system according to claim 138, wherein the 3D covering
comprises at least a portion with a kink radius of from about 5
millimeter (mm) to about 100 mm.
140. The system according to claim 138, wherein the 3D covering
comprises at least a portion with a kink radius of from about 10 mm
to about 20 mm.
141. The system according to any claim herein, wherein the 3D
covering comprises fibers with a width and/or diameter from about
10 .mu.m to about 1 mm.
142. The system according to claim 141, wherein the 3D covering
comprises fibers with a width and/or diameter from about 20 .mu.m
to about 500 .mu.m.
143. The system according to claim 141, wherein the 3D covering
comprises fibers with a width and/or diameter from about 50 .mu.m
to about 100 .mu.m.
144. The system according to any claim herein, wherein at least a
portion of the 3D covering comprises a greater axial compliance
than radial compliance.
145. The system according to claim 144, wherein the at least a
portion of the 3D covering comprises a majority of fibers that are
circumferentially oriented.
146. The system according to any claim herein, wherein at least a
portion of the 3D covering comprises relatively equal axial
compliance and radial compliance.
147. The system according to claim 146, wherein the at least a
portion of the 3D covering comprises a majority of fibers that are
anisotropically oriented.
148. The system according to any claim herein, wherein the 3D
covering comprises a material selected from the group consisting
of: fiber reinforced material; particle reinforced material; flake
reinforced material; a multi-layered material; a segmented
material; and any combination thereof.
149. The system according to any claim herein, further comprising a
user interface.
150. The system according to claim 149, wherein the system is
configured to display an image of the tubular conduit on the user
interface.
151. The system according to claim 150, wherein the displayed image
is a 3D image.
152. The system according to claim 150, wherein the system is
configured to allow a user to modify the displayed image.
153. The system according to claim 149, wherein the system is
configured to display an image of a proposed 3D covering.
154. The system according to claim 153, wherein the displayed image
is a 3D image.
155. The system according to claim 153, wherein the system is
configured to allow a user to modify the displayed image.
156. The system according to claim 149, wherein the user interface
comprises a user control comprising an electronic model modifying
tool.
157. The system according to claim 156, wherein the tool is
configured to modify a model of the tubular conduit.
158. The system according to claim 156, wherein the tool is
configured to modify a model of a proposed 3D covering.
159. The system according to claim 156, wherein the tool comprises
a property modifying function selected from the group consisting
of: smooth; erase; spline; fillet, fill; insert a building block;
and any combination thereof.
160. The system according to claim 159, wherein the tool comprises
a property modifying function including inserting a building block,
the building block comprising an electronic model selected from the
group consisting of: anastomosis; dimple; reinforcing spline; and
any combination thereof.
161. The system according to claim 149, wherein the tool is
configured to measure distance.
162. The system according to claim 149, wherein the construction
signal is based on information provided by a user of the system via
the user interface.
163. The system according to any claim herein, wherein the material
delivery device further comprises a modification assembly
configured to modify at least one of the 3D covering or the tubular
conduit.
164. The system according to claim 163, wherein the modification
assembly is configured to deliver energy to at least one of the 3D
covering or the tubular conduit.
165. The system according to claim 164, wherein the energy
comprises heat and/or cooling.
166. The system according to claim 163, wherein the modification
assembly is configured to deliver a second material to at least one
of the 3D covering or the tubular conduit.
167. The system according to claim 166, wherein the second material
comprises a material selected from the group consisting of:
solvent; drug; agent; and any combination thereof.
168. The system according to claim 163, wherein the modification
assembly is configured to deliver moisture to at least one of the
3D covering or the tubular conduit.
169. The system according to any claim herein, further comprising a
target onto which the material is delivered.
170. The system according to claim 169, wherein the target
comprises a mandrel configured to rotate.
171. The system according to claim 169, wherein the material
delivery device is constructed and arranged to produce the
target.
172. The system according to claim 169, wherein the target
comprises a disposable component.
173. The system according to any claim herein, further comprising a
sterile barrier constructed and arranged to maintain sterility
between the material delivery device and one or more other portions
of the system.
174. A graft device produced by a system of any claim herein,
wherein the graft device comprises: a tubular conduit; a 3D
covering surrounding the tubular conduit, wherein the 3D covering
is produced by a material delivery device based on image data of
the tubular conduit.
175. The graft device according to any claim herein, wherein the
tubular conduit comprises a discrete feature and the 3D covering
comprises at least one customized portion positioned relative to
the discrete feature.
176. A method of producing a graft device using the system of any
claim herein.
177. The method according to any claim herein, comprising: (1)
producing image data of a tubular conduit; (2) receiving the image
data of the tubular conduit and creating an electronic model of the
tubular conduit; (3) creating an electronic model of a 3D covering;
(4) delivering material to produce a 3D covering.
178. The method according to claim 177, further comprising
modifying the electronic model of the tubular conduit produced in
(2).
179. The method according to claim 177, further comprising
modifying the electronic model of the 3D covering produced in
(3).
180. The method according to claim 177, wherein the 3D covering is
produced in (4) by delivering the material onto the tubular
conduit.
181. The method according to claim 177, further comprising: (5)
placing the 3D covering about the tubular conduit.
182. The system according to claim 99, wherein the material
comprises the glycosaminoglycan, and wherein the glycosaminoglycan
comprises heparin, heparan sulfate, chondroitin sulfate, dermatan
sulfate, keratan sulfate, and/or hyaluronic acid, or any
combination thereof.
183. The system according to claim 99, wherein the material
comprises the proteoglycan, and wherein the proteoglycan comprises
decorin, biglycan, testican, bikunin, fibromodulin, lumican,
versican, perlecan, neurocan, aggrecan and/or brevican.
Description
CROSS-REFERENCE
[0001] This application claims the benefit of U.S. Provisional
Application Ser. No. 62/348,318, filed Jun. 10, 2016, the contents
of which are incorporated herein in their entirety.
BACKGROUND
[0002] Devices in the field of rapid prototyping, using 3D computer
aided design (CAD) data, can be used to produce various
three-dimensional (3D) structures. These devices use geometric
data, either as 3D solid models, or 2D slices using a scanning
device, to produce a scale model, a physical part, or an assembly
via either an additive or subtractive manufacturing method.
[0003] In the field of tissue engineering, 3D printers are used to
produce scaffolds, which can be subsequently seeded with cells,
cultured ex vivo, and then implanted as tissue replacements.
Another approach is 3D bioprinting, which can be used to fabricate
living tissue constructs by incorporating living cells into a
scaffold created during the fabrication process.
[0004] Current 3D printed implants are not customized to conform to
patient specific anatomical geometries, resulting in various
limitations. There is a need for improved graft devices, and other
three-dimensional implantable structures, that provide long term
efficacy and safety.
SUMMARY
[0005] For these and other reasons, there is a general need for
systems, devices and methods that can provide enhanced implantable
devices for mammalian patients. Desirably, the systems, devices and
methods may improve long term efficacy and minimize surgical and
device complications such as those caused by improper or inadequate
production of an implantable device.
[0006] Embodiments of the systems, devices and methods described
herein can be directed to systems, devices and methods for
producing graft devices and other devices for implanting in
mammalian patients, as well as to the implantable devices
themselves.
[0007] According to an aspect of the present disclosure, a system
for producing a graft device for a patient may comprise an imaging
device configured to produce image data of a tubular conduit, and a
processing unit configured to receive the image data from the
imaging device. The processing unit can comprise an algorithm, the
algorithm configured to process the image data, and produce a
construction signal based on the image data. The system may
comprise a material delivery device configured to receive the
construction signal from the processor, and deliver material to
produce a 3D covering based on the construction signal. The graft
device may comprise the 3D covering positioned about the tubular
conduit.
[0008] In some cases, the material delivery device may be
configured to deliver the 3D covering onto the tubular conduit. In
some cases, the 3D covering may be configured to be positioned
about the tubular conduit after being produced by the material
delivery device. In some cases, the graft device may comprise a
coronary artery bypass graft. In some cases, the graft device may
comprise a dialysis graft.
[0009] In some cases, the graft device may comprise an implant
selected from the group consisting of: artery bypass graft;
coronary artery bypass graft; dialysis graft; peripheral arterial
bypass graft; great vessel replacement; great vessel bypass graft;
esophageal graft; tracheal graft; bronchial graft; biliary duct
graft; intestinal graft; organ transplant vascular connection
graft; neuronal replacement implant; ligament graft; ligament
replacement; tendon graft; tendon replacement; transplant organ
coating; fallopian tube; urethra; ureter; cartilage; hip joint;
shoulder joint; intervertebral disc; menisci; and any combination
thereof.
[0010] In some cases, the imaging device may comprise a device
selected from the group consisting of: computerized tomography (CT)
imager; optical coherence tomography (OCT) imager; magnetic
resonance imaging (MRI); 3D Scanner; Camera; Infrared Camera;
Ultrasound imager; and any combination thereof.
[0011] In some cases, the image data may comprise information
related to the tubular conduit. In some cases, the image data may
comprise information related to a portion of the patient's anatomy.
In some cases, the image data may comprise data collected when the
tubular conduit is in-situ. The image data can comprise data
collected after the tubular conduit is harvested from the patient.
In some cases, the image data may comprise data collected after the
tubular conduit is harvested from the patient. In some cases, the
image data may comprise data selected from the group consisting of:
surface topography data; surface geometry data; periphery data;
length data; diameter data; thickness data such as wall thickness
data; taper data; eccentricity data; relative position data;
trajectory data; speed of motion data; relative angle data;
radiopacity data; blood flow data; echographic data; spectroscopic
data; and any combination thereof.
[0012] In some cases, the image data may comprise at least one
discrete feature of the tubular conduit. The at least one discrete
feature can be identified by the algorithm. The at least one
discrete feature can comprise a feature selected from the group
consisting of: sidebranch; recess; projection; end; end portion;
bend portion; lobe; bifurcation; trifurcation; a dilated portion; a
swollen portion; valve; a tapered portion; a location of a surgical
staple; an angled portion; a calcified tissue portion; an
atheromatous tissue portion; a partially occluded portion; a fully
occluded portion; and any combination thereof. The at least one
discrete feature can comprise a sidebranch. The image data can
include sidebranch information selected from the group consisting
of: location; diameter; taper angle; ligation device position;
ligation device geometry; ligation device type; and any combination
thereof.
[0013] In some cases, the image data may comprise information
related to the compliance of the tubular conduit. In some cases,
the image data may comprise information related to the shape of the
tubular conduit changing over time. The information related to the
shape of the tubular conduit changing over time can comprise
information related to the shape of the tubular conduit changing
over time prior to harvesting. The tubular conduit can change shape
due to a change in a parameter selected from the group consisting
of: blood pressure; respiration; patient movement; and any
combination thereof.
[0014] In some cases, the tubular conduit may comprise tissue
selected from the group consisting of: cylindrical tissue; organ
tissue; saphenous vein; vein; artery; urethra; intestine;
esophagus; ureter; trachea; bronchi; duct; fallopian tube; and any
combination thereof. In some cases, the tubular conduit may
comprise tissue selected from the group consisting of: bone;
ligament; tendon; and any combination thereof In some cases, the
tubular conduit may comprise artificial material.
[0015] In some cases, the processing unit may comprise memory
circuitry. The memory circuitry can be configured to store
information selected from the group consisting of: tissue type;
type of the material; information regarding the application of the
graft device; information regarding use of one or more tools;
compliance information; density information; strength information;
modulus of elasticity information; elastic limit information; wall
thickness information; shrinkage information of the material; cure
time information of the material; spacing to a mandrel and/or other
target; minimum bend radius of the covering; maximum ovality of the
covering; and any combination thereof. The construction signal can
be based on information stored in the memory circuitry. In some
cases, the processing unit may comprise at least one of a
microprocessor or a microcontroller.
[0016] In some cases, the algorithm may be configured to identify
at least one discrete feature of the tubular conduit. The at least
one discrete feature of the tubular conduit identified by the
algorithm can comprise a feature selected from the group consisting
of: sidebranch; recess; projection; end; end portion; bend portion;
lobe; bifurcation; trifurcation; a dilated portion; a swollen
portion; valve; a tapered portion; a location of a surgical staple;
an angled portion; a calcified tissue portion; an atheromatous
tissue portion; a partially occluded portion; a fully occluded
portion; and any combination thereof. The 3D covering can comprise
at least one customized portion positioned relative to the at least
one discrete feature. The customized portion can be positioned
proximate the at least one discrete feature. The algorithm can be
configured to identify at least two discrete features of the
tubular conduit, and the 3D covering can comprise at least two
customized portions. The customized portion can comprise a
differentiating property selected from the group consisting of:
different thickness; different material; different porosity;
different pore size; different compliance in one or more
directions; different level of conformality; different texture;
different alignment and/or orientation of the deposited material;
different stiffness; different fiber diameter; addition of a
kink-resisting element; addition of an agent; and any combination
thereof. The at least one discrete feature can comprise a
protrusion of the tubular conduit. The protrusion can comprise a
sidebranch. The 3D covering can comprise a customized portion
including a void proximate the protrusion. The void can comprise a
hole. The void can comprise a recess. The at least one customized
portion can comprise a portion selected from the group consisting
of: a portion comprising a change in deposition of the material
such as to mechanically reinforce and/or provide a strain relief at
a sidebranch location; a portion configured to constrain a
sidebranch such as to minimize hemodynamic disruption in a lumen of
the tubular conduit; and any combination thereof. The 3D covering
can comprise a customized portion including a fillet positioned
proximate the at least one discrete feature. The at least one
discrete feature can comprise an end of the tubular conduit. The 3D
covering can comprise a customized portion including a taper
located proximate the end of the tubular conduit. The at least one
discrete feature can comprise a second end of the tubular conduit,
and the 3D covering can comprise a second customized portion
including a second tapered positioned proximate the second end of
the tubular conduit. The 3D covering can comprise a customized
portion including a reinforced portion located proximate the end of
the tubular conduit. The 3D covering can comprise a customized
portion including an optimized anastomosis portion located
proximate the end of the tubular conduit. The optimized anastomosis
portion can comprise an optimized shape. The optimized anastomosis
portion can comprise an optimized structure. The at least one
discrete feature can comprise tissue whose softness is above a
threshold. The customized portion can comprise a differentiating
property selected from the group consisting of: different material;
different compliance; different thickness; different permeability;
different porosity; different anisotropy; and any combination
thereof. The at least one discrete feature can comprise tissue
whose flexibility is above a threshold. The customized portion can
comprise a differentiating property selected from the group
consisting of: different material; different compliance; different
thickness; different permeability; different porosity; different
anisotropy; and any combination thereof. The at least one discrete
feature can comprise tissue whose shape changes over time. The
customized portion can comprise a differentiating property selected
from the group consisting of: different material; different
compliance; different thickness; different permeability; different
porosity; different anisotropy; and any combination thereof. The 3D
covering can include a customized portion including a reinforced
portion. The at least one discrete feature can comprise a
thin-walled portion of the tubular conduit, and the customized
portion can be located proximate the thin-walled portion. The 3D
covering can include a customized portion including a strain
relief. The at least one discrete feature can comprise at least one
of an end of the tubular conduit or a bend portion of the graft
device, and the customized portion can be located proximate the at
least one discrete feature. The 3D covering can include a
customized portion including modified porosity. The at least one
discrete feature can comprise an anastomosis site and/or a segment
of high curvature of the graft device, and the customized portion
can be located proximate the at least one discrete feature. The 3D
covering can include a customized portion including a modified
compliance. The modified compliance can comprise a modified radial
compliance. The modified compliance can comprise a modified axial
compliance. The at least one discrete feature can comprise an
anastomosis site, a ligament attachment site, a tendon attachment
site and/or a site of segmented compliance, and the customized
portion can be located proximate the at least one discrete
feature.
[0017] In some cases, the algorithm may be configured to create a
3D model of the tubular conduit based on the image data. The 3D
model can comprise a spatial model. The algorithm can be configured
to modify the 3D model of the tubular conduit. The image data can
comprise multiple slices of a CT image. In some cases, the
algorithm may be configured to create a 3D model of a proposed 3D
cover.
[0018] In some cases, the algorithm may be configured to create a
proposed 3D model of the 3D covering, and to modify the proposed 3D
model to create a final 3D model of the 3D covering. The algorithm
can be configured to modify the proposed 3D model based on at least
one discrete feature of the tubular conduit. The algorithm can be
configured to modify the proposed 3D model based on user input.
[0019] In some cases, the algorithm may be configured to create a
3D model of at least one of the tubular conduit or the 3D covering
based on boundary conditions. The algorithm can be configured to
optimize hemodynamics within the tubular conduit by performing a
function selected from the group consisting of: reducing flow
turbulence; controlling bending radius; controlling lumen geometry;
controlling a transition; controlling a taper; controlling a bend
portion; controlling tortuosity; controlling wall shear; preventing
buckling; optimizing wall shear stress; modifying an end portion to
optimize an anastomotic connection; reducing geometric mismatch
near an anastomotic connection; and any combination thereof.
[0020] In some cases, the algorithm may be configured to convert
information from an imaging coordinate system to a material
deposition coordinate system. The imaging coordinate system can
comprise Cartesian coordinates and the material deposition
coordinate system can comprise a cylindrical, spherical and/or
curvilinear coordinate system.
[0021] In some cases, the material delivery device may comprise at
least one nozzle, and the algorithm may be configured to create a
pathway of motion for the at least one nozzle. The algorithm can
create the pathway of motion based on one or more off limits
locations. The pathway of motion can avoid portions of the 3D
covering that have already been created. The pathway of motion can
avoid the tubular conduit. The material delivery device can
comprise a mandrel, and the pathway of motion can avoid the
mandrel. The pathway of motion can minimize dissipation of heat to
the tubular conduit. The pathway of motion can reduce multiple
passes of delivery of material in neighboring regions of the
tubular conduit within a time period.
[0022] In some cases, the algorithm may be configured to perform a
self-diagnostic. The system can comprise at least one sensor
configured to produce a signal, and the self-diagnostic can be
based on the signal from the at least one sensor. The sensor can
comprise one or more sensors selected from the group consisting of:
an optical sensor; a laser; a magnetic sensor; an electrical
sensor; an energy sensor; a pressure sensor; a force sensor; a
strain gauge; a position sensor; a flow sensor; a sound sensor; an
ultrasound sensor; a humidity sensor; and any combination thereof.
The self-diagnostic can be configured to assess a parameter
selected from the group consisting of: electrical connection
status; rotational speed; translational speed; nozzle status;
material delivery status; temperature; chamber environment
condition; energy delivered; home position; a distance between two
components of the system; and any combination thereof.
[0023] In some cases, the algorithm may be configured to create the
construction signal based on a property of the tubular conduit. The
construction signal can produce a 3D covering that provides
mechanical support to the tubular conduit. The construction signal
can produce a 3D covering with varied properties along a length of
the tubular conduit.
[0024] In some cases, the material delivery device may comprise at
least one nozzle. The material delivery device can comprise at
least two nozzles. In some cases, the material delivery device may
comprise a 3D printer. In some cases, the material delivery device
may be configured to deliver the material using an additive
printing process. In some cases, the material delivery device may
be configured to deliver the material as a series of layers.
[0025] In some cases, the material delivery device may comprise a
device selected from the group consisting of: a 3D printer; a layer
printing device; an electrospinning device; a melt-spinning device;
a melt-electrospinning device; a misting assembly; a sprayer; an
electrosprayer; a fused deposition device; a selective laser
sintering device; a fiber dispenser; a wire dispenser; a thread
dispenser; a resin deposition device, such as a UV-curable resin
deposition device; a stereolithography device; a phase separation
device; a wet spinning device; a dip coating device; a lathe; a
milling machine; a chemical etching device; a plasma etching
device; a negative mold-over device; an injection molding device;
and any combination thereof. The material delivery device can
comprise two or more devices selected from the group consisting of:
a 3D printer; a layer printing device; an electrospinning device; a
melt-spinning device; a melt-electrospinning device; a misting
assembly; a sprayer; an electrosprayer; a fused deposition device;
a selective laser sintering device; a fiber dispenser; a wire
dispenser; a thread dispenser; a resin deposition device, such as a
UV-curable resin deposition device; a stereolithography device; a
phase separation device; a wet spinning device; a dip coating
device; a lathe; a milling machine; a chemical etching device; a
plasma etching device; a negative mold-over device; an injection
molding device; and any combination thereof.
[0026] In some cases, the material may comprise one or more
materials selected from the group consisting of: synthetic polymer;
natural polymer; protein; metal; metal alloy; collagen; elastin; a
glycosaminoglycan (e.g. heparin, heparan sulfate, chondroitin
sulfate, dermatan sulfate, keratan sulfate, and/or hyaluronic
acid); a proteoglycan (e.g. decorin, biglycan, testican, bikunin,
fibromodulin, lumican, versican, perlecan, neurocan, aggrecan
and/or brevican); an alginate; cellulose; gelatin; silk fibroin;
fibrinogen; chitosan; an enzyme; fibronectin; glycerin; integrin;
keratin; a vitamin; a carbohydrate; a monosaccharide; a
disaccharide; a polysaccharide; a nucleoside; abductin; lignin; a
glycolipid; a phospholipid; a sterol; shrilk; cobalt-chrome;
nitinol; aluminum oxide; magnesium; iron; zinc; steel; titanium;
vitalium; alacrite; platinum; gold; silver; copper; manganese; a
polyester; a polyurethane; a polycarbonate; a polyether; a
polysulfone; a polyamide; a polyetheramide; a polystyrene; a
polybutadiene; a polyisoprene; a poly(methyl methacrylate); a
polyanhydride; a polydimethylsiloxane; a polydioxanone;
polyethylene; glycol; polyethylene terephthalate; a polyglycolide;
a polyhydroxyalkanoate; polyimide; polytetrafluoroethylene;
polyvinylidene fluoride; polyethylene; polypropylene;
polyvinylfluoride; polyvinylchloride; polyacylonitrile; silicone; a
ceramic; a bioceramic; a bioglass; a composite material; and any
combination thereof.
[0027] In some cases, the 3D covering may comprise varied
properties along its length. The 3D covering can comprise at least
one customized portion. In some cases, the 3D covering may comprise
at least a portion with a thickness from about 10 micrometers
(.mu.m) to about 1 centimeter (cm). The 3D covering can comprise at
least a portion with a thickness from about 50 .mu.m to about 500
.mu.m. The 3D covering can comprise at least a portion with a
thickness from about 200 .mu.m to about 300 .mu.m.
[0028] In some cases, the 3D covering may comprise at least a
portion with a bulk porosity less than about 99%. The 3D covering
can comprise at least a portion with a bulk porosity from about 1%
to about 90%. The 3D covering can comprise at least a portion with
a bulk porosity from about 10% to about 80%. The 3D covering can
comprise at least a portion with a bulk porosity from about 30% to
about 80%. The 3D covering can comprise at least a portion with a
bulk porosity from about 50% to about 70%.
[0029] In some cases, the 3D covering may comprise a length from
about 1 millimeter (mm) to about 1 meter (m). The 3D covering can
comprise a length from about 3 cm to about 50 cm. The 3D covering
can comprise a length from about 20 cm to about 30 cm.
[0030] In some cases, the 3D covering may comprise at least a
portion with a compliance under a physiologic load that is less
than about 99%. The 3D covering can comprise at least a portion
with a compliance under a physiologic load that is from about 1% to
about 50%. The 3D covering can comprise at least a portion with a
compliance under a physiologic load that may be from about 10% to
about 25%.
[0031] In some cases, the 3D covering may comprise at least a
portion with an ultimate strength from about 0.1 megapascal (MPa)
to about 500 MPa. The 3D covering can comprise at least a portion
with an ultimate strength from about 0.5 MPa to about 100 MPa. The
3D covering can comprise at least a portion with an ultimate
strength from about 1 MPa to about 10 MPa.
[0032] In some cases, the 3D covering may comprise at least a
portion with a biodurability from about 1 hour to about 10 years.
The 3D covering can comprise at least a portion with a
biodurability from about 48 hours to about 2 years. The 3D covering
can comprise at least a portion with a biodurability from about 3
months to about 6 months.
[0033] In some cases, the 3D covering may comprise a drug, and the
3D covering can be configured to release the drug for a duration
from about 1 hour to about 10 years. The 3D covering can be
configured to release the drug for a duration from about 48 hours
to about 2 years. The 3D covering can be configured to release the
drug for a duration from about 3 months to about 6 months.
[0034] In some cases, the 3D covering may comprise at least a
portion with a macropore size from about 10 .mu.m to about 1000
.mu.m. The 3D covering can comprise at least a portion with a
macropore size from about 20 .mu.m to about 200 .mu.m. The 3D
covering can comprise at least a portion with a macropore size from
about 50 .mu.m to about 100 .mu.m.
[0035] In some cases, the 3D covering may comprise at least a
portion with a macropore spacing from about 10 .mu.m to about 1000
.mu.m. The 3D covering can comprise at least a portion with a
macropore spacing from about 100 .mu.m to about 500 .mu.m. The 3D
covering can comprise at least a portion with a macropore spacing
from about 200 .mu.m to about 400 .mu.m.
[0036] In some cases, the 3D covering may comprise at least a
portion with a water permeability of less than about 300 milliliter
per centimeter squared per minute (ml/cm2/min). The 3D covering can
comprise at least a portion with a water permeability from about 50
ml/cm2/min to about 200 ml/cm2/min. The 3D covering can comprise at
least a portion with a water permeability from about 100 ml/cm2/min
to about 150 ml/cm2/min.
[0037] In some cases, the 3D covering may comprise a texture with
from about 0.25 nanometer (nm) to about 50 .mu.m roughness value
Ra. The 3D covering can comprise a texture with from about 0.2
.mu.m to about 12.5 .mu.m roughness value Ra. The 3D covering can
comprise a texture with from about 1.6 .mu.m to about 6.3 .mu.m
roughness value Ra.
[0038] In some cases, the 3D covering may comprise a suture
retention strength up to about 1 kilogram-force (Kgf). The 3D
covering can comprise a suture retention strength of from about 50
gram-force (gf) to about 500 gf. The 3D covering can comprise a
suture retention strength of between 100 gf and 200 gf.
[0039] In some cases, the 3D covering may comprise at least a
portion with a kink radius of up to about 1 meter (m). The 3D
covering can comprise at least a portion with a kink radius of from
about 5 mm to about 100 mm. The 3D covering can comprise at least a
portion with a kink radius of from about 10 mm to about 20 mm.
[0040] In some cases, the 3D covering may comprise fibers with a
width and/or diameter from about 10 .mu.m to about 1 mm. The 3D
covering can comprise fibers with a width and/or diameter from
about 20 .mu.m to about 500 .mu.m. The 3D covering can comprise
fibers with a width and/or diameter from about 50 .mu.m to about
100 .mu.m.
[0041] In some cases, at least a portion of the 3D covering may
comprise a greater axial compliance than radial compliance. The at
least a portion of the 3D covering can comprise a majority of
fibers that are circumferentially oriented.
[0042] In some cases, at least a portion of the 3D covering may
comprise an axial compliance that is relatively equal to its radial
compliance. The at least a portion of the 3D covering can comprise
a majority of fibers that are anisotropically oriented.
[0043] In some cases, the 3D covering may comprise a material
selected from the group consisting of: fiber reinforced material;
particle reinforced material; flake reinforced material; a
multi-layered material; a segmented material; and any combination
thereof.
[0044] In some cases, the system may comprise a user interface. The
system can be configured to display an image of the tubular conduit
on the user interface. The displayed image can be a 3D image. The
system can be configured to allow a user to modify the displayed
image. The system can be configured to display an image of a
proposed 3D covering. The displayed image can be a 3D image. The
system can be configured to allow a user to modify the displayed
image. The user interface can comprise a user control comprising an
electronic model modifying tool. The tool can be configured to
modify a model of the tubular conduit. The tool can be configured
to modify a model of a proposed 3D covering. The tool can comprise
a property modifying function selected from the group consisting
of: smooth; erase; spline; fillet, fill; insert a building block;
and any combination thereof. The tool can comprise a property
modifying function including inserting a building block, the
building block comprising an electronic model selected from the
group consisting of: anastomosis; dimple; reinforcing spline; and
any combination thereof. The tool can be configured to measure
distance. The construction signal can be based on information
provided by a user of the system via the user interface.
[0045] In some cases, the material delivery device may comprise a
modification assembly configured to modify at least one of the 3D
covering or the tubular conduit. The modification assembly can be
configured to deliver energy to at least one of the 3D covering or
the tubular conduit. The energy can comprise heat and/or cooling.
The modification assembly can be configured to deliver a second
material to at least one of the 3D covering or the tubular conduit.
The second material can comprise a material selected from the group
consisting of: solvent; drug; agent; and any combination thereof.
The modification assembly can be configured to deliver moisture to
at least one of the 3D covering or the tubular conduit.
[0046] In some cases, the system may comprise a target onto which
the material is delivered. The target can comprise a mandrel
configured to rotate. The material delivery device can be
constructed and arranged to produce the target. The target can
comprise a disposable component.
[0047] In some cases, the system may comprise a sterile barrier
constructed and arranged to maintain sterility between the material
delivery device and one or more other portions of the system.
[0048] According to another aspect of the present disclosure, a
graft device may be produced by a system as described herein. The
graft device may comprise a tubular conduit and a 3D covering
surrounding the tubular conduit, and the 3D covering may be
produced by a material delivery device of the system. The material
delivery device may produce the 3D covering based on image data of
the tubular conduit. The tubular conduit can comprise a discrete
feature, and the 3D covering can comprise at least one customized
portion positioned relative to the discrete feature.
[0049] According to another aspect of the present disclosure, a
method of producing a graft device uses a system as described
herein. The method may comprise (1) producing image data of a
tubular conduit, (2) receiving the image data of the tubular
conduit and creating an electronic model of the tubular conduit,
(3) creating an electronic model of a 3D covering and (4)
delivering material to produce a 3D covering. The method can
comprise modifying the electronic model of the tubular conduit
produced in (2). The system can comprise modifying the electronic
model of the 3D covering produced in (3). The method 3D covering
produced in (4) can be produced by delivering the material onto the
tubular conduit (e.g. directly onto the tubular conduit). The
method can comprise a (5) including placing the 3D covering about
the tubular conduit.
[0050] The technology described herein, along with the attributes
and attendant advantages thereof, may best be appreciated and
understood in view of the following detailed description taken in
conjunction with the accompanying drawings in which representative
embodiments are described by way of example.
INCORPORATION BY REFERENCE
[0051] All publications, patents, and patent applications herein
are incorporated by reference to the same extent as if each
individual publication, patent, or patent application was
specifically and individually indicated to be incorporated by
reference. To the extent publications and patents or patent
applications incorporated by reference contradict the disclosure
contained in the specification, the specification is intended to
supersede or take precedence over any such contradictory
material.
BRIEF DESCRIPTION OF THE DRAWINGS
[0052] FIG. 1 illustrates a schematic view of a system for
producing a graft device.
[0053] FIG. 1A illustrates a side sectional view of a graft device
comprising a covering including multiple customized portions.
[0054] FIG. 1B illustrates a side sectional view of a graft device
comprising a covering including a large proportion of isotropically
oriented fibers.
[0055] FIG. 1C illustrates a side sectional view of a graft device
comprising a covering including a large proportion of
circumferentially oriented fibers.
[0056] FIG. 2 illustrates a flow chart of a method of producing a
graft device using the system of FIG. 1.
[0057] FIG. 3 illustrates a schematic view of a particular
embodiment of the system of FIG. 1.
DETAILED DESCRIPTION
[0058] Reference will now be made in detail to the present
embodiments of the technology, examples of which are illustrated in
the accompanying drawings. The same reference numbers are used
throughout the drawings to refer to the same or like parts.
[0059] It may be further understood that the words "comprising"
(and any form of comprising, such as "comprise" and "comprises"),
"having" (and any form of having, such as "have" and "has"),
"including" (and any form of including, such as "includes" and
"include") or "containing" (and any form of containing, such as
"contains" and "contain") when used herein, specify the presence of
stated features, integers, steps, operations, elements, and/or
components, but may not preclude the presence or addition of one or
more other features, integers, steps, operations, elements,
components, and/or groups thereof.
[0060] As used herein, the term "about" may mean the referenced
numeric indication plus or minus 15% of that referenced numeric
indication.
[0061] It may be understood that, although the terms first, second,
third etc. may be used herein to describe various limitations,
elements, components, regions, layers and/or sections, these
limitations, elements, components, regions, layers and/or sections
may not be limited by these terms. These terms may only be used to
distinguish one limitation, element, component, region, layer or
section from another limitation, element, component, region, layer
or section. Thus, a first limitation, element, component, region,
layer or section discussed below may be termed a second limitation,
element, component, region, layer or section without departing from
the teachings of the present application.
[0062] It may be further understood that when an element may be
referred to as being "on", "attached", "connected" or "coupled" to
another element, it can be directly on or above, or connected or
coupled to, the other element, or one or more intervening elements
can be present. In contrast, when an element may be referred to as
being "directly on", "directly attached", "directly connected" or
"directly coupled" to another element, there may be no intervening
elements present. Other words used to describe the relationship
between elements may be interpreted in a like fashion (e.g.
"between" versus "directly between," "adjacent" versus "directly
adjacent," etc.).
[0063] It may be further understood that when a first element may
be referred to as being "in", "on" and/or "within" a second
element, the first element can be positioned: within an internal
space of the second element, within a portion of the second element
(e.g. within a wall of the second element); positioned on an
external and/or internal surface of the second element; and any
combination thereof.
[0064] As used herein, the term "proximate" may generally refer to
locations relatively close to, on, in and/or within a referenced
component or other location.
[0065] Spatially relative terms, such as "beneath," "below,"
"lower," "above," "upper" and the like may generally refer to an
element and/or feature's relationship to another element(s) and/or
feature(s) as, for example, illustrated in the figures. It may be
understood that the spatially relative terms may be intended to
encompass different orientations of the device in use and/or
operation in addition to the orientation depicted in the figures.
For example, if the device in a figure may be turned over, elements
described as "below" and/or "beneath" other elements or features
may then be oriented "above" the other elements or features. The
device can be otherwise oriented (e.g. rotated about 90 degrees or
at other orientations) and the spatially relative descriptors used
herein interpreted accordingly.
[0066] As described herein, "room pressure" may generally refer to
a pressure of the environment surrounding the systems and devices
as described herein. Positive pressure may include pressure above
room pressure or simply a pressure that may be greater than another
pressure, such as a positive differential pressure across a fluid
pathway component such as a valve. Negative pressure may include
pressure below room pressure or a pressure that may be less than
another pressure, such as a negative differential pressure across a
fluid component pathway such as a valve. Negative pressure can
include a vacuum but does not imply a pressure below a vacuum. As
used herein, the term "vacuum" can be used to refer to a full or
partial vacuum, or any negative pressure as described herein.
[0067] The term "diameter" may generally refer to a non-circular
geometry and in some cases may be taken as the diameter of a
hypothetical circle approximating the geometry being described. For
example, when describing a cross section, such as the cross section
of a component, the term "diameter" may be taken to represent the
diameter of a hypothetical circle with the same cross sectional
area as the cross section of the component being described.
[0068] The terms "major axis" and "minor axis" of a component may
generally refer to the length and diameter, respectively, of the
smallest volume hypothetical cylinder which can completely surround
the component.
[0069] The terms "reduce", "reducing", "reduction" and the like,
may generally refer to a reduction in a quantity, including a
reduction to zero. Reducing the likelihood of an occurrence may
include prevention of the occurrence.
[0070] The term "and/or" where used herein may be taken as specific
disclosure of each of the two specified features or components with
or without the other. For example "A and/or B" may be to be taken
as specific disclosure of each of (i) A, (ii) B and (iii) A and B,
just as if each may be set out individually herein.
[0071] The term "biodurability" may in some cases generally refer
to a preservation of one or more physical properties, one or more
mechanical properties, one or more chemical properties, or any
combination thereof during an exposure to a biological environment
or a biologically similar environment over a period of time. In
some cases, a period of time may comprise an extended period of
time. In some cases, a period of time may comprise about 1 month,
about 6 months, about 1 year, about 2 years, about 5 years, about
10 years or more. A biological environment may comprise a surface
of a subject. A biological environment may comprise an internal
surface or internal volume of a subject. A biologically similar
environment may comprise an artificial setting such as a media
solution or incubator environment that simulates a biological
environment.
[0072] The term "bulk porosity" may in some cases generally refer
to a bulk porosity of a material or structure, such as a processed
material or structure. A bulk porosity may be equivalent to
1-W/(.mu.V) where W equals a weight of a material or structure,
.mu. may be the weight per unit volume of a material or structure
prior to a processing, and V may be the volume of the material or
structure, such as the processed material or structure.
[0073] The term "macropore" may in some cases generally refer to a
lumen through a wall of a structure (such as a matrix) having a
cross sectional area of at least about 3E-4 millimeters squared
(mm.sup.2), at least about 3E-3 mm.sup.2, or at least about 1E-2
mm.sup.2.
[0074] The term "kink radius" may in some cases generally refer to
an inner radius of a structure (such as a tube) measured when the
structure may be bent to a limit before buckling may occur.
[0075] It is appreciated that certain features of the invention,
which are, for clarity, described in the context of separate
embodiments, may also be provided in combination in a single
embodiment. Conversely, various features of the invention which
are, for brevity, described in the context of a single embodiment,
may also be provided separately or in any suitable sub-combination.
For example, it may be appreciated that all features set out in any
of the claims (whether independent or dependent) can be combined in
any given way.
[0076] Provided herein are medical devices for implantation in a
mammalian patient, as well as systems, devices and methods for
producing these medical devices. The medical devices can comprise
graft devices that are implanted to carry fluids (e.g. blood or
other body fluid) from a first anatomical location to a second
anatomical location of the patient. The graft devices may include a
conduit or other implantable structure ("conduit" herein), such as
a harvested blood vessel segment or other tubular conduit, other
harvested tissue and/or an artificial conduit, and a
three-dimensional (3D) covering that surrounds the conduit. The
systems can comprise a material delivery device configured to
produce the 3D covering (e.g. directly onto the conduit or
fabricated separately for subsequent placement about the conduit).
The systems described herein can include a processing unit that
receives image data related to the patient's anatomy, such as image
data related to an organ or other tissue. In some cases, the image
data may be related to a tubular conduit or other tissue of a
patient (e.g. data from one or more images of an in-vivo tubular
tissue conduit and/or from images of an already harvested tubular
tissue conduit). The processing unit can produce a construction
signal based on the image data, the construction signal used by the
material delivery device to produce the 3D covering.
[0077] Referring now to FIG. 1, a system for creating an
implantable device for a patient is illustrated. System 10 may
comprise processing unit 200 and a material delivery device (MDD)
300. System 10 may be constructed and arranged to produce an
implantable device, such as graft device 100 which may comprise a
three-dimensional (3D) covering, covering 110, which can be
positioned about an implantable structure, conduit 120, such as a
tubular conduit or other implantable structure. System 10 can
comprise an imaging device, such as imager 400 shown, which
produces image data 410. Image data 410 can represent information
related to conduit 120 and/or a portion of a patient's anatomy
(e.g. a portion of the patient's cardiovascular system).
[0078] Processing unit 200 may be configured to receive image data
410 from imager 400. Imager 400 can comprise an imaging device
selected from the group consisting of: CT imager; OCT imager; MRI;
3D Scanner; camera; infrared camera; ultrasound imager;
laser-scanning device; and any combination thereof. Imager 400 can
produce image data 410 (e.g. image data of conduit 120 and/or any
portion of the patient's anatomy), and processing unit 200 can
receive the image data 410 from imager 400.
[0079] Image data 410 can be collected from an in-situ conduit 120
(e.g. a vein, artery or other blood vessel, prior to being
harvested) and/or after conduit 120 has been harvested from the
patient. In some cases, image data 410 may comprise data collected
both prior to and after a conduit 120 has been harvested from the
patient. Image data 410 can comprise various geometric and other
information of conduit 120, such as data selected from the group
consisting of: surface topography data; surface geometry data;
periphery data; length data; diameter data; thickness data such as
wall thickness data; taper data; eccentricity data; relative
position data; trajectory data; speed of motion data; relative
angle data; radiopacity data; blood flow data; echographic data;
spectroscopic data; and any combination thereof. Image data 410 can
comprise data related to one or more abnormalities or other
particular, relatively discrete, features of conduit 120, feature
121. In the embodiment shown in FIG. 1, conduit 120 may comprise
feature 121 comprising a sidebranch. In some cases, feature 121 of
conduit 120 can comprise one or more discrete features selected
from the group consisting of: sidebranch; recess; projection; end;
end portion; bend portion (e.g. a region of bending); lobe;
bifurcation; trifurcation; a dilated portion; a swollen portion;
valve; a tapered portion; a location of a surgical staple; an
angled portion; a calcified tissue portion; an atheromatous tissue
portion; a partially occluded portion; a fully occluded portion;
and any combination thereof. In some cases, image data 410 can
comprise sidebranch data selected from the group consisting of:
location; diameter; taper angle; and any combination thereof. One
or more sidebranches of conduit 120 may include a ligation device
(e.g. suture or a ligation clip placed after harvest of conduit
120), and image data 410 can include information related to the
position of the ligation device, ligation device geometry and/or
ligation device type.
[0080] Processing unit 200 can comprise one or more algorithms,
algorithm 250. Processing unit 200 can be configured to receive,
process (e.g. mathematically process), store and/or transmit data.
Processing unit 200 can be configured to receive image data 410
from imaging device 400, and algorithm 250 can be configured to
process the received image data 410 to produce a construction
signal, construction signal 201. Construction signal 201 can
comprise geometry and other construction information used by
material delivery device (MDD) 300 to produce covering 110.
Construction signal 201 can be based on one or more properties of
conduit 120 (e.g. as determined by algorithm 250). Construction
signal 201 can be configured to produce a covering 110 that has
varied properties along the length of covering 110, such as to
provide mechanical support for conduit 120 at one or more
particular locations. MDD 300 can receive construction signal 201
from processing unit 200, and deliver one or more materials,
material 350, to produce covering 110 based on construction signal
201. In some cases, MDD 300 may deliver material 350 directly onto
conduit 120 while producing covering 110. In some cases, covering
110 may be positioned about conduit 120 after covering 110 is
produced by MDD 300.
[0081] Conduit 120 can comprise living tissue (including previously
harvested tissue), such as one or more segments of tissue selected
from the group consisting of: cylindrical tissue; organ tissue;
saphenous vein; vein; artery; urethra; intestine; esophagus;
ureter; trachea; bronchi; duct; fallopian tube; and any combination
thereof. In some cases, conduit 120 can comprise an artificial
material (e.g. a plastic or other non-tissue tube or other
structure). In some cases, conduit 120 may comprise a first length
of tissue that may be subsequently shortened (e.g. one or more ends
cut off) during the creation of graft device 100. In some cases,
conduit 120 may comprise a single lumen structure of tissue. In
some cases, conduit 120 may comprise a tubular structure including
at least a bifurcation or trifurcation of lumens. In some cases,
conduit 120 may comprise bone, ligament and/or tendon tissue.
Conduit 120 can comprise one or more discrete features 121 as
described above, such as a discrete feature 121 that may be
identified by algorithm 250 (e.g. identified by analyzing image
data 410).
[0082] Graft device 100 can be used as an arterial bypass graft,
such as to be used as a coronary artery bypass graft. In some
cases, graft device 100 may be configured for use as a dialysis
graft. In some cases, graft device 100 may comprise one or more
graft devices configured to be used as graft selected from the
group consisting of: artery bypass graft; coronary artery bypass
graft; dialysis graft; peripheral arterial bypass graft; great
vessel replacement; great vessel bypass graft; esophageal graft;
tracheal graft; bronchial graft; biliary duct graft; intestinal
graft; organ transplant vascular connection graft; neuronal
replacement implant; ligament graft; ligament replacement; tendon
graft; tendon replacement; transplant organ coating; fallopian
tube; urethra; ureter; cartilage; hip joint; shoulder joint;
intervertebral disc; menisci; and any combination thereof.
[0083] As described herein, covering 110 may include varied
properties along its length, such as when covering 110 comprises
one or more customized portions 111. In some cases, one or more
customized portions 111 may be provided based on image data 410
(e.g. as determined by algorithm 250). In some cases, one or more
customized portions 111 may be included proximate one or more
discrete features 121.
[0084] In some cases, covering 110 and/or one or more customized
portions 111 may comprise a parameter with a value selected from
Range 1, Range 2 and/or Range 3 of Table 1 below. Note that the
value of one parameter from one range may not necessarily be linked
to the same range of a different parameter.
TABLE-US-00001 TABLE 1 Feature Range 1 Range 2 Range 3 Thickness 10
.mu.m to 1 cm 50 .mu.m to 500 .mu.m 200 .mu.m to 300 .mu.m Bulk
Porosity 0% to 99% 30% to 80% 50% to 70% Length 1 mm to 1 m 3 cm to
50 cm 20 cm to 30 cm Conformality of Constrictive to loose
Restrictive to loose Restrictive - covering 110 to fitting - entire
length fitting - entire length or local conduit 120 or local
portion entire length or local portion thereof thereof portion
thereof Compliance under a 0% to 99% 1% to 50% 10% to 25%
physiologic load such as arterial pressure Ultimate Strength 0.1
MPa to 500 MPa 0.5 MPa to 100 MPa 1 MPa to 10 MPa Biodurability 1
hour to 10 years 48 hours to 2 years 3 months to 6 months Drug
release 1 hour to 10 years 48 hours to 2 years 3 months to 6 months
duration (i.e. when impregnated with a drug or other agent)
Macropores (1) Size (1) 10 .mu.m to (1) 20 .mu.m to 200 .mu.m (1)
50 .mu.m to 100 .mu.m 1000 .mu.m (2) Spacing (2) 10 .mu.m to (2)
100 .mu.m to 500 .mu.m (2) 200 .mu.m to 400 .mu.m 1000 .mu.m Water
Permeability 0 mL/cm.sup.2/min to 50 mL/cm.sup.2/min to 100
mL/cm.sup.2/min to 300 mL/cm.sup.2/min 200 mL/cm.sup.2/min 150
mL/cm.sup.2/min Texture (Roughness 0.025 nm to 50 .mu.m 0.2 .mu.m
to 12.5 .mu.m 1.6 .mu.m to 6.3 .mu.m values Ra) Suture retention 0
gf to 1 Kgf 50 gf to 500 gf 100 gf to 200 gf strength Kink
resistance 0 mm to 1 m 5 mm to 100 mm 10 mm to 20 mm (kink radius)
Fiber width and/or 10 .mu.m to 1 mm 20 .mu.m to 500 .mu.m 50 .mu.m
to 100 .mu.m diameter
[0085] In some cases, covering 110 can comprise a compliance, C,
that may be equal (e.g. relatively equal) in both axial and
tangential directions (C.sub.axial=C.sub.tangential), such as is
described herein in reference to FIG. 1C. In some cases, covering
110 can comprise different axial compliance than its
circumferential (i.e. tangential) compliance, such as when covering
110 may comprise high circumferential compliance and low axial
compliance (C.sub.axial<C.sub.tangential), or when covering 110
may comprise high axial compliance and low circumferential
compliance (C.sub.axial>C.sub.tangential), such as is described
herein in reference to FIG. 1C. In some cases, covering 110 may
comprise homogeneous materials, such as materials including
homopolymers, copolymers, pure metals and/or metal alloys. In some
cases, covering 110 may comprise composite materials, such as fiber
reinforced, particle reinforced, flake reinforced, multi-layered,
and/or segmented materials.
[0086] In some cases, material delivery device (MDD) 300 may
comprise a device configured to produce covering 110 by delivering
material 350 using an additive printing process, such as a process
similar to that performed by commercially available 3D printers. In
some cases, MDD 300 may deliver material 350 in a series of layers
to produce covering 110. In some cases, MDD 300 may deliver
material 350 as a fiber. In some cases, MDD 300 may deliver
material 350 onto a surface, such as mandrel 320 shown, to produce
covering 110, after which covering 110 may be positioned about
conduit 120. In some cases, MDD 300 may produce covering 110 by
delivery of material 350 directly onto conduit 120 (e.g. while
mandrel 320 may be positioned within conduit 120). In some cases, a
first portion of covering 110 may be produced by delivery of
material 350 onto conduit 120, and a second portion of covering 110
may be produced by delivery of material 350 onto a surface (e.g.
mandrel 320). In some cases, the second portion of covering 110 can
subsequently be positioned about conduit 120 and/or the first
portion of covering 110.
[0087] In some cases, MDD 300 may comprise a device configured to
also produce a target (e.g. a template used to produce covering
110), such as when MDD 300 may create mandrel 320. The outer
geometry of mandrel 320 may define the inner surface geometry of
covering 110, and MDD 300 can be configured to produce a customized
mandrel 320, such as to create a covering 110 comprising one or
more customized portions 111. In some cases, mandrel 320 may be
disposed of after the creation of covering 110. In some cases,
mandrel 320 can be used to create multiple coverings 110.
[0088] In some cases, MDD 300 may comprise one, two or more devices
selected from the group consisting of: a 3D printer; a layer
printing device; an electrospinning device; a melt-spinning device;
a melt-electrospinning device; a misting assembly; a sprayer; an
electrosprayer; a fused deposition device; a selective laser
sintering device; a fiber dispenser; a wire dispenser; a thread
dispenser; a resin deposition device, such as a UV-curable resin
deposition device; a stereolithography device; a phase separation
device; a wet spinning device; a dip coating device; a lathe; a
milling machine; a chemical etching device; a plasma etching
device; a negative mold-over device; an injection molding device;
and any combination thereof. In some cases, MDD 300 and/or other
components of system 10 may be constructed and arranged as
described herein in reference to FIG. 3. For example, MDD 300 can
comprise a modification assembly, such as modification assembly 605
described herein in reference to FIG. 3, such as to apply or
otherwise direct toward covering 110, conduit 120 and/or mandrel
320 energy or material selected from the group consisting of:
light; heat; cooling; moisture; solvent; drug or other agent; and
any combination thereof.
[0089] Material delivery device (MDD) 300 can comprise one, two or
more nozzles or other material delivery elements, nozzle 310. MDD
300 can be configured to translate, rotate and/or otherwise
reposition nozzle 310 along a pathway. Nozzle 310 can comprise two
or more concentric nozzles. MDD 300 can be configured to control
the delivery of material through the one or more nozzles 310, such
as to control the speed of material 350 delivered to nozzle 310
and/or control the cross sectional shape and/or area of nozzle
310.
[0090] Material 350 may comprise one or more materials configured
for implantation in a patient. Material 350 can comprise one, two
or more materials selected from the group consisting of: synthetic
polymer; natural polymer; protein; metal; metal alloy; collagen;
elastin; a glycosaminoglycan (e.g. heparin, heparan sulfate,
chondroitin sulfate, dermatan sulfate, keratan sulfate, and/or
hyaluronic acid); a proteoglycan (e.g. decorin, biglycan, testican,
bikunin, fibromodulin, lumican, versican, perlecan, neurocan,
aggrecan and/or brevican); an alginate; cellulose; gelatin; silk
fibroin; fibrinogen; chitosan; an enzyme; fibronectin; glycerin;
integrin; keratin; a vitamin; a carbohydrate; a monosaccharide; a
disaccharide; a polysaccharide; a nucleoside; abductin; lignin; a
glycolipid; a phospholipid; a sterol; shrilk; cobalt-chrome;
nitinol; aluminum oxide; magnesium; iron; zinc; steel; titanium;
vitalium; alacrite; platinum; gold; silver; copper; manganese; a
polyester; a polyurethane; a polycarbonate; a polyether; a
polysulfone; a polyamide; a polyetheramide; a polystyrene; a
polybutadiene; a polyisoprene; a poly(methyl methacrylate); a
polyanhydride; a polydimethylsiloxane; a polydioxanone;
polyethylene; glycol; polyethylene terephthalate; a polyglycolide;
a polyhydroxyalkanoate; polyimide; polytetrafluoroethylene;
polyvinylidene fluoride; polyethylene; polypropylene;
polyvinylfluoride; polyvinylchloride; polyacylonitrile; silicone; a
ceramic; a bioceramic; a bioglass; a composite material and any
combination thereof.
[0091] As described herein, material delivery device (MDD) 300 can
include a mandrel or other target, mandrel 320. In some cases,
mandrel 320 may provide a support structure onto which material 350
may be delivered by nozzle 310. In some cases, conduit 120 may be
positioned over mandrel 320 and material 350 may be delivered onto
conduit 120 while mandrel 320 may be in place. In some cases,
mandrel 320 may be configured to rotate, translate and/or otherwise
move in relation to nozzle 310 (e.g. via motion of mandrel 320
and/or motion of nozzle 310). In some cases, mandrel 320 may
comprise a flat or irregularly shaped surface onto which material
350 may be delivered to produce covering 110. In some cases, MDD
300 may be configured to produce one or more mandrels 320, such as
when a subset of mandrels or each mandrel 320 may be disposable
(e.g. used for a limited time such as to produce a single covering
110). In some cases, nozzle 310 can comprise a first nozzle 310a
which may be used to produce a mandrel 320 and a second nozzle 310b
which may be used to apply material 350 onto mandrel 320 to produce
covering 110.
[0092] In some cases, MDD 300 may comprise a barrier 390, such as a
sterile barrier configured to maintain sterility between one or
more portions of MDD 300 and one or more sterile components of
system 10. Barrier 390 can comprise a sterile drape (e.g. a sterile
plastic drape) and/or a molded sterile covering (e.g. a molded
plastic covering). In some cases, one or more portions of MDD 300
may be sterile (e.g. sterilizable).
[0093] Processing unit 200 can comprise one or more electrical or
other components, such as one or more of processor 210, memory 220,
circuitry 230 and/or a user interface (UI) 240, all shown.
Processing unit 200 can comprise one or more algorithms, algorithm
250. Processor 210 can comprise a microprocessor or other
microcontroller configured to perform a series of events (e.g.
events whose outcome may be determined by status of a parameter or
outcome of a previous event). Memory 220 can comprise volatile or
non-volatile electronic memory used to temporarily or permanently
store information. In some cases, memory 220 may comprise a library
of information. For example, memory 220 can store information
selected from the group consisting of: tissue type; material 350
type; information regarding the application (e.g. clinical
application) of graft device 100; information regarding use of one
or more tools, such as tool 260 described herein; compliance
information; density information; strength information; modulus of
elasticity information; elastic limit information; wall thickness
information; material 350 shrinkage and/or cure time at varying
temperature and/or relative humidity; spacing to mandrel 320 or
other target; minimum bend radius of covering 110; maximum ovality
of covering 110; and any combination thereof. Construction signal
201 can be based, at least partially, on information stored in
memory 220. Circuitry 230 may comprise one or more of analog and/or
digital electronic componentry common to electromechanical,
microprocessor controlled equipment.
[0094] UI 240 can comprise one or more user input and/or user
output components selected from the group consisting of: switch;
keyboard; membrane keypad; knob; lever; touchscreen; light such as
an LED; display; audio transducer such as a buzzer or speaker;
tactile transducer such as an eccentric rotational element; and any
combination thereof. In some cases, UI 240 can comprise a display
such that an image (e.g. a 2D or 3D image) of all or a portion of
conduit 120 can be provided to a user of system 10. In some cases,
a user can modify the image of conduit 120, via one or more input
components of UI 240. In some cases, UI 240 can display a proposed
(e.g. for modification by the user) or actual (i.e. final) image
(e.g. a 2D or 3D image) of all or a portion of covering 110. In
some cases, construction signal 201 may be at least partially based
on information provided by a user via UI 240.
[0095] User interface (UI) 240 and/or another component of
processing unit 200 or system 10 can comprise one or more tools
configured to allow adjustment of a parameter or other information,
tool 260 shown. In some cases, tool 260 may be configured to allow
a user to modify an electronic model of conduit 120 (e.g. a model
displayed on UI 240). In some cases, tool 260 may be configured to
allow a user to modify an electronic model of covering 110 (e.g. a
proposed or final model of covering 110 that may be displayed on UI
240). In some cases, tool 260 may provide a property modifying
function selected from the group consisting of: smooth; erase;
spline; fillet, fill; insert a building block (e.g. a geometric
structure to the model); and any combination thereof. In some
cases, tool 260 may be configured to allow a user to insert a
building block comprising an electronic model selected from the
group consisting of: anastomosis; dimple (e.g. to accommodate a
sidebranch); reinforcing spline; and any combination thereof In
some cases, tool 260 may be configured to measure a distance (e.g.
a length, width, diameter, taper, radius of curvature and/or
thickness).
[0096] In some cases, a user of system 10 may enter information via
UI 240, and construction signal 201 may be based at least in part
on that information. For example, a user can enter information that
creates a customized portion 111 and/or positions a customized
portion 111 along covering 110. In some cases, algorithm 250 may
produce a construction signal 201 that may be based both on image
data 410 and information provided by a user via UI 240.
[0097] Algorithm 250 can be configured to analyze one or more
portions of image data 410 and may produce construction signal 201
based on the analysis. The analysis of image data 410 by algorithm
250 can include analysis of other information, such as information
stored in memory 220 and/or information provided by a user via user
interface (UI) 240. Using image data 410 and/or such other
information, algorithm 250 can produce mathematical models,
geometric models, thresholds, boundary conditions and other
information relevant to the creation of construction signal 201. In
some cases, construction signal 201 may be based on both image data
410 and other information, such as information stored in memory 220
and/or information input by a user of system 10 via UI 240. In some
cases, algorithm 250 may be configured to produce a spatial model
and/or other three-dimensional model of conduit 120 based on image
data 410 (e.g. image data including multiple slices of a CT image
or other multi-dimensional information produced by imaging device
400). In some cases, a user of system 10 can modify the
three-dimensional model of conduit 120, such as by using one or
more controls or tools of UI 240.
[0098] In some cases, algorithm 250 may be configured to produce a
point cloud, surface model and/or other three-dimensional model of
a "proposed" covering 110, such as to enable one or more
modifications of the model to be made prior to producing a
construction signal 201 used to produce covering 110 for graft
device 100. The one or more modifications of the model can be
performed automatically by algorithm 250 (e.g. based on one or more
identified discrete features 121 of conduit 120) and/or manually by
a user of system 10 (e.g. based on user input). In some cases,
algorithm 250 may be configured to produce a model of a covering
110 (proposed and/or final), based on one or more boundary
conditions (e.g. to optimize hemodynamics by reducing flow
turbulence, controlling bending radius, controlling lumen geometry;
controlling a transition; controlling a taper; controlling a bend
portion; controlling tortuosity; controlling wall shear; preventing
buckling, optimizing wall shear stress; modifying an end portion to
optimize an anastomotic connection; and/or reducing geometric
mismatch near an anastomotic connection). In some cases, algorithm
250 may be configured to convert data from an imaging coordinate
system (e.g. coordinate system of imaging device 400 and/or image
data 410) to data in a material deposition coordinate system (e.g.
a coordinate system of MDD 300). In some cases, the imaging
coordinate system may comprise a Cartesian coordinate system and
the material deposition coordinate system may comprise a
cylindrical, spherical and/or curvilinear coordinate system.
[0099] In some cases, algorithm 250 may be configured to identify a
feature of conduit 120, such as feature 121 described herein.
Algorithm 250 can be configured to create (e.g. via construction
signal 201) a customized portion 111 of covering 110, the
customized portion 111 surrounding or at least proximate that
particular feature 121 of conduit 120. A subset of customized
portions or each customized portion 111 can comprise a property
that is different than another portion of covering 110 (e.g.
different than the majority of covering 110). Customized portion
111 can comprise one, two or more portions that have a
differentiating property selected from the group consisting of:
different (e.g. increased and/or decreased) thickness; different
material; different porosity; different pore size; different
compliance in one or more directions (e.g. axially and/or
radially); different level of conformality; different texture;
different alignment and/or orientation of material (e.g. fiber)
deposition); different stiffness; different fiber diameter;
addition of a kink-resisting element; addition of an agent such as
a growth factor or pharmaceutical agent; and any combination
thereof.
[0100] In some cases, covering 110 may comprise one or more
customized portions 111 which may be customized to cover a
protrusion (e.g. a sidebranch or other protrusion) of conduit 120
and/or a ligation device may be used to occlude a sidebranch of
conduit 120, such as sidebranch-accommodating portion 111a shown.
Portion 111a can have a geometry configured to accommodate the
sidebranch and/or a ligation device without compromising an
internal lumen of conduit 120, such as by creating a space (e.g. a
recess or hole in covering 110) in which the sidebranch and/or
ligation device may be located. In some cases, one or more
customized portions 111 positioned proximate a sidebranch can
comprise one or more of: a portion comprising a change (e.g. an
increase) in deposition of material 350 such as to mechanically
reinforce and/or provide a strain relief at a sidebranch location;
a portion configured to constrain a sidebranch such as to minimize
hemodynamic disruption in a lumen of conduit 120 (e.g. to cause a
slightly greater restriction around bulbous sidebranches or
varicosity to force more material towards the lumen and reduce
irregularities within the lumen); and any combination thereof. In
some cases, a customized portion 111 can include at least a portion
that is positioned away from but proximate a sidebranch location,
such as a portion of conduit 120 that may include a void region
(e.g. a hole and/or recess), such as when algorithm 250 produces a
construction signal 201 that may include a customized portion 111
that fills the void proximate the sidebranch.
[0101] In some cases, covering 110 may comprise one or more
customized portions 111 which comprise a fillet (i.e. rounded
interior corner) of covering 110, such as fillet portion 111b shown
and positioned in covering 110 to be located proximate a sidebranch
location of conduit 120 when covering 110 may be positioned about
conduit 120.
[0102] In some cases, covering 110 may comprise one or more
customized portions 111 which may be positioned proximate to (e.g.
on or near), or otherwise positioned relative to, a discrete
feature 121 comprising an end of covering 110, such as a customized
portion 111 to be positioned proximate an end of conduit 120 when
covering 110 may be positioned about conduit 120. For example,
customized portion 111 can comprise a tapered portion of covering
110, such as tapered portion 111c shown. Tapered portion 111c can
be positioned at one or more ends of covering 110, such as to
create a non-conforming portion of customized portion 111 (e.g. a
space exists between covering 110 and conduit 120 at tapered
portion 111c, such as to allow for radial expansion of conduit 120
at that location). In some cases, customized portion 111 can
comprise a reinforced portion (e.g. a thicker portion or a portion
including more durable materials), such as reinforced portion 111d
shown. Reinforced portion 111d can be positioned at one or more
ends of covering 110, and can be combined with tapered portion 111c
at either or both ends. In some cases, one or more reinforced
portions 111d may be positioned about a mid-portion of covering
110, or at any feature 121 of conduit 120, such as when a
reinforced portion 111d may be positioned at a thin-walled portion
of conduit 120. In some cases, a customized portion 111 to be
located proximate an end of conduit 120 can be optimized for an
anastomotic connection, such as to include an optimized shape (e.g.
optimized shape for an anastomosis), optimized structural support,
optimized material, optimized permeability, optimized porosity,
optimized thickness, optimized biodurability, inclusion of agents
such as growth factors or pharmaceutical drugs to be delivered to
anastomosis and/or other optimized characteristic for performing
and maintaining an anastomotic connection. In some cases, conduit
120 and its associated covering 110 may comprise three or more
ends, such as when a bifurcated, trifurcated or other multiple
branched graft device may be being constructed. One of more ends,
such as each end (such as each of three or more ends) can include a
customized portion 111 as described herein. In some cases, tapered
portion 111c, reinforced portion 111d and/or another customized
portion 111 can be configured as a strain-relief, such as a strain
relief to be located proximate an end or bend portion of graft
device 100.
[0103] Image data 410 can include information related to the
compliance of one or more portions of conduit 120, such as when
algorithm 250 may identify a discrete feature 121 comprising tissue
whose softness and/or flexibility may be above a threshold. In some
cases, a customized portion 111 can comprise material, compliance,
thickness, permeability, porosity and/or anisotropy that is
different than other portions of covering 110. Algorithm 250 can
analyze image data 410 and identify one or more shape changes of
conduit 120 that occur over time (e.g. a pre-harvested, in-situ
conduit 120 that may change shape due to change in blood pressure,
respiration and/or patient movement). In some cases, customized
portion 111 can comprise an expandable geometry, a "loose-fitting"
geometry and/or a compliance matching that of conduit 120.
Algorithm 250 can analyze image data 410 and identify a customized
portion 111 of covering 110 that has a modified (e.g. increased
and/or decreased) porosity. For example, covering 110 may have a
customized portion 111 of modified porosity proximate a discrete
feature 121 of conduit 120, such as a discrete feature 121
comprising an anastomosis site (e.g. an end portion of conduit
120), and/or a segment of high curvature. Algorithm 250 can analyze
image data 410 and identify a customized portion 111 of covering
110 that may have a modified compliance (e.g. increased and/or
decreased compliance in a radial and/or axial direction). For
example, covering 110 may have a portion 111 of modified compliance
proximate a discrete feature 121 of conduit 120, such as a discrete
feature 121 comprising an anastomosis site (e.g. an end portion of
conduit 120 or a mid-portion for a side-to-side anastomosis), a
ligament and/or tendon attachment site (e.g. when graft device 100
comprises an implant configured to function as ligament and/or a
tendon), a site of segmented compliance (e.g. for radial
reinforcement, kink resistance and/or peristaltic flow), and/or any
combination thereof.
[0104] In some cases, algorithm 250 may be configured to create
and/or modify (generally "create") a pathway of motion of a
material delivery portion of MDD 300 (e.g. nozzle 310). For
example, algorithm 250 can be configured to avoid one or more "off
limits" locations, such as positions to be avoided that are stored
in memory 220. In some cases, algorithm 250 may be configured to
create a pathway of motion that may avoid one or more portions of
system 10, as described by way of example herein. Algorithm 250 can
be configured to create a pathway of motion that may avoid
previously-produced partial portions of covering 110 while
completing the production of covering 110. As described above, in
some cases, covering 110 may be produced by delivery of material
350 onto conduit 120. In some cases, algorithm 250 can be
configured to create a pathway of motion that avoids contact with
conduit 120. As described above, in some cases, covering 110 may be
produced by delivery of material 350 onto and/or at least toward a
surface or tube, such as mandrel 320 described above (e.g. with or
without conduit 120 in place). In some cases, algorithm 250 can be
configured to create a pathway of motion that avoids contact with
mandrel 320.
[0105] As described above, in some cases, covering 110 may be
produced by delivery of material 350 onto conduit 120. In some
cases, algorithm 250 can be configured to create a pathway of
motion that avoids damaging (e.g. thermally damaging) conduit 120
(e.g. when the delivery of material 350 is at an elevated
temperature), such as by minimizing heat dissipation to conduit 120
during delivery of material 350. For example, algorithm 250 can be
configured to create a pathway of motion that avoids multiple
passes of delivery of material 350 onto conduit 120 in neighboring
regions within a time period (i.e. to allow cooling or otherwise
avoid undesired accumulation of thermal energy in any one small
portion of conduit 120).
[0106] In some cases, algorithm 250 may be configured to perform a
self-diagnostic. Algorithm 250 can be configured to perform a
self-diagnostic, such as a self-diagnostic based on signals from
one or more sensors of system 10, such as a sensor 209 of
processing unit 200, a sensor 309 of material delivery device (MDD)
300 and/or a sensor 409 of imaging device 400. Sensors 209, 309
and/or 409 may individually or any combination thereof comprise one
or more sensors selected from the group consisting of: an optical
sensor; a laser; a magnetic sensor; an electrical sensor; an energy
sensor; a pressure sensor; a force sensor; a strain gauge; a
position sensor; a flow sensor; a sound sensor; an ultrasound
sensor; a humidity sensor; and any combination thereof. For
example, algorithm 250 can perform a self-diagnostic to assess a
parameter of MDD 300 selected from the group consisting of:
electrical connection status; rotational speed; translational
speed; nozzle 310 status; material delivery status; temperature
(e.g. via a thermocouple of other sensor of system 10); chamber
environment condition (e.g. temperature or relative humidity as
measured by a sensor of system 10); energy delivered (e.g. laser
energy delivered); home position; a distance between two components
of MDD 300; and any combination thereof.
[0107] Referring additionally to FIG. 1A, a side sectional view of
a graft device comprising a covering including multiple customized
portions is illustrated. Covering 110 may be positioned about
conduit 120. In some cases, covering 110 may be produced by MDD 300
delivery of material directly on conduit 120. In some cases,
covering 110 can be produced by MDD 300 separate from conduit 120
(e.g. onto mandrel 320 or other surface), and subsequently
positioned about conduit 120. In some cases, covering 110 may have
an internal profile that conformally surrounds conduit 120, such as
is shown in FIG. 1A except in the area of the customized portion,
tapered portion 111c. In some cases, there may be space between one
or more portions of covering 110 and conduit 120, such as one or
more spaces positioned proximate one or more ends of conduit 120
(e.g. to allow expansion of an end portion or other portion of
conduit 120 prior to contacting covering 110), such as is shown at
tapered portion 111c.
[0108] In some cases, covering 110 may comprise fibers that are
oriented to provide constraint against radial expansion that may be
greater than the constraint against axial expansion, such as by
aligning fibers of covering 110 more in the radial direction than
in the axial direction.
[0109] Referring additionally to FIG. 1B, a side sectional view of
a graft device comprising a covering including a large proportion
of isotropically oriented fibers is illustrated. Covering 110 is
shown positioned about conduit 120, such as when material 350 is
delivered directly onto conduit 120 and/or when covering 110 may be
produced and subsequently placed about conduit 120. Covering 110 of
FIG. 1B may include at least a portion comprising a matrix of
fibers whose orientation may be primarily isotropic, such that
expansion in all directions may be relatively uniform.
[0110] Referring additionally to FIG. 1C, a side sectional view of
a graft device comprising a covering including a larger proportion
of circumferentially oriented fibers is illustrated. Covering 110
is shown positioned about conduit 120, such as when material 350
may be delivered directly onto conduit 120 and/or when covering 110
may be produced and subsequently placed about conduit 120. Covering
110 of FIG. 1C may include at least a portion comprising a matrix
of fibers whose orientation is primarily in a relatively
circumferential direction, such that expansion of covering 110 (and
graft device 100) may be more limited in a radial direction than in
an axial direction.
[0111] Referring now to FIG. 2, a flow chart of a method for
producing a graft device is illustrated. Method 1000 may comprise a
series of steps of producing a graft device using system 10
described herein in reference to FIG. 1. In STEP 1010, an image of
a conduit 120 (e.g. a blood vessel or other tubular conduit) may be
made, such as via imaging device 400 to produce image data 410. In
STEP 1020, processing unit 200 may receive the image data 410, such
as to create a 3D electronic model (e.g. a CAD or other electronic
model) of conduit 120. In some cases, an STEP 1025 may be
performed, in which the 3D electronic model of conduit 120 may be
modified, such as automatically by algorithm 250 and/or manually by
a user of system 10 via user interface (UI) 240.
[0112] In STEP 1030, an electronic model of a proposed covering 110
may be created by processing unit 200. In some cases, algorithm 250
may create the electronic model of the proposed covering 110 based
on information selected from the group consisting of: identified
discrete features 121 of conduit 120; information stored in memory
220; information input by a user via UI 240; and any combination
thereof. In some cases, an STEP 1035 may be performed, in which the
electronic model of the proposed covering 110 may be adjusted, such
as an adjustment performed by a user of system 10 via UI 240.
[0113] In STEP 1040, covering 110 may be produced by material
delivery device (MDD) 300. In some cases, covering 110 may be
produced by delivery of material 350 directly onto conduit 120. In
some cases, covering 110 may be produced separate from conduit 120
(e.g. on a surface, tube or other mandrel 320), and subsequently
positioned about conduit 120 (e.g. in the STEP 1045). In some
cases, a mandrel 320 may be produced by MDD 300 as described
herein.
[0114] Referring now to FIG. 3, a schematic view of a system for
producing an implantable device is illustrated. System 10 may
include various components and assemblies (hereinafter
"components") used to produce an implantable device, such as graft
device 100 shown. System 10 may comprise processing unit 200,
material delivery device (MDD) 300 and imager 400, and one or more
of these can be of similar construction and arrangement and/or
include similar components to those described herein in reference
to FIG. 1. Imager 400 may comprise an imaging device and may
produce image data 410. Image data 410 can represent geometric and
other information related to conduit 120 (e.g. a blood vessel,
other tubular conduit and/or other patient tissue) and/or any
portion of a patient's anatomy. Processing unit 200 can include
algorithm 250, which can be used to produce a construction signal
201 based on the image data 410. MDD 300 can comprise a material
delivery device used to produce an implantable device that is based
on construction signal 201. For example, MDD 300 can deliver one or
more materials, material 350, to produce an implantable device, and
the pattern of the delivery of the material 350 can be based on
construction signal 201 (and correspondingly based on image data
410). In some cases, MDD 300 may produce a covering 110 which may
be positioned about conduit 120 to produce graft device 100.
Covering 110 can be positioned about conduit 120 after covering 110
may be produced by MDD 300, or MDD 300 can deliver material 350
directly onto conduit 120 while producing covering 110.
[0115] Graft device 100 can be constructed and arranged to perform
or otherwise function as a bypass graft, such as a coronary artery
bypass graft or a peripheral artery bypass graft. In some cases,
graft device 100 is constructed and arranged as a neo-vessel, such
as a neo-artery and/or a neo-vein. Conduit 120 can include living
tissue and/or artificial materials. In some cases, conduit 120 may
comprise living tissue (e.g. harvested tissue), such as a segment
or other portion of tissue selected from the group consisting of:
saphenous vein; vein; artery; urethra; intestine; esophagus;
ureter; trachea; bronchi; duct; fallopian tube; and any combination
thereof or other tissues. In some cases, conduit 120 can comprise
an artificial material selected from the group consisting of:
polytetrafluoroethylene (PTFE); expanded PTFE (ePTFE); polyester;
polyvinylidene fluoride/hexafluoropropylene (PVDF-HFP); silicone;
polyethylene; polypropylene; polyester-based polymer;
polyether-based polymer; thermoplastic rubber; and any combination
thereof or other materials. Graft device 100 may comprise first end
101, second end 102, and a lumen 103 extending from first end 101
to second end 102. System 10 may include a material delivery
device, MDD 300, may be configured to deliver material 350 to
produce covering 110. Material 350 can comprise a biocompatible
material such as a biocompatible metal and/or plastic. Material 350
can comprise a first material 351 (e.g. a polymer) and a second
material 352 (e.g. a solvent).
[0116] Material delivery device (MDD) 300 can comprise a 3D
printing device. In some cases, MDD 300 may comprise a device
selected from the group consisting of: a 3D printer; a layer
printing device; an electrospinning device; a melt-spinning device;
a melt-electrospinning device; a misting assembly; a sprayer; an
electrosprayer; a fused deposition device; a selective laser
sintering device; a fiber dispenser; a wire dispenser; a thread
dispenser; a resin deposition device, such as a UV-curable resin
deposition device; a stereolithography device; a phase separation
device; a wet spinning device; a dip coating device; a lathe; a
milling machine; a chemical etching device; a plasma etching
device; a negative mold-over device; an injection molding device;
and any combination thereof. In some cases, MDD 300 may comprise a
second material delivery device, such as a material delivery device
selected from the group consisting of: an electrospinning device; a
melt-spinning device; a melt-electrospinning device; a misting
assembly; a sprayer; an electrosprayer; a fuse deposition device; a
selective laser sintering device; a three-dimensional printer; and
any combination thereof. In some cases, second material 352 or
another portion of material 350 may comprise a solvent or other
material that may be desired to be removed before covering 110 may
be implanted in the patient. In some cases, system 10 can be
configured to remove second material 352 (e.g. a solvent),
accelerate the removal of second material 352 and/or at least
reduce the amount of second material 352 present in conduit 120,
covering 110, graft device 100, chamber 20 and/or another component
of system 10 (hereinafter "remove second material 352" or "remove
solvent"). In some cases, system 10 can be configured to reduce
injury to the conduit 120 by one or more solvents (e.g. reduce
injury to living tissue such as living vein tissue). System 10 can
include one or more sensors, such as sensors 26, 36, 329, 309, 369
and/or 606 shown and described in detail herein. Sensors 26, 36,
329, 309, 369 and/or 606 can provide a signal related to the
creation of covering 110 (e.g. related to the presence of one or
more solvents and/or a signal otherwise used to perform a
solvent-reducing process and/or to reduce injury to a conduit 120
by one or more solvents).
[0117] System 10 can include a mandrel 320 and a material delivery
device (MDD) 300 can comprise a rotating assembly 340 configured to
rotate mandrel 320. In the embodiment shown in FIG. 3, mandrel 320
may be slidingly inserted into conduit 120, and subsequently
engaged with rotating assembly 340. In some cases, covering 110 may
be produced on mandrel 320 (e.g. material 350 is delivered onto
mandrel 320), as described herein in reference to FIG. 1. In some
cases, covering 110 may be produced without the use of mandrel 320.
MDD 300 can include material dispenser 301 configured to dispense
one or more materials, such as material 350 shown. Material 350 can
comprise one or more materials as described herein in reference to
FIG. 1. Material 350 can include a mixture of one or more first
materials 351 (e.g. one or more polymers), one or more second
materials 352 (e.g. one or more solvents) and/or other materials
used to produce covering 110. Material 350 can comprise a cartridge
or other reservoir surrounding first material 351 and/or second
material 352, the reservoir being fluidly attachable to material
dispenser 301 by an operator of system 10.
[0118] System 10 can include an environmentally controllable
chamber, chamber 20 shown, which surrounds at least a portion of
mandrel 320 (e.g. surrounding at least conduit 120 and covering 110
during the creation of graft device 100). Chamber 20 can surround
one or more portions of material delivery assembly 305 and/or
modification assembly 605 described herein. In some cases, chamber
20 may comprise a disposable cartridge and/or at least a portion of
chamber 20 is disposable (e.g. used to create implants for a single
patient). Chamber 20 can be configured to remove solvents or other
potentially harmful materials (collectively "remove solvent"
herein) during and/or after production of covering 110.
[0119] System 10 may include controller 30 which is configured to
provide control signals and/or receive information signals.
Controller 30 can be configured to control one or more of: material
delivery assembly 305 (e.g. to control the flow rate of material
350 into material delivery assembly 305); rotating assembly 340
(e.g. to control the rotation of mandrel 320); linear drive
assembly 345 (e.g. to control the translation rate or position of
material delivery assembly 305); modification assembly 605 (e.g. to
control delivery of material by modification assembly 605, delivery
of energy by modification assembly 605 and/or removal of a portion
of covering 110 by modification assembly 605); linear drive
assembly 645 (e.g. to control the translation rate or position of
modification assembly 605); voltage applied to mandrel 320 (e.g.
voltage provided by power supply 302); and any combination thereof.
Controller 30 can comprise environmental controller 35.
Environmental controller 35 can be configured to remove solvents.
In some cases, environmental controller 35 can be configured to
control an environmental parameter within chamber 20, such as an
environmental parameter selected from the group consisting of:
temperature; humidity; pressure; solvent concentration; and any
combination thereof. Environmental controller 35 or another
component of controller 30 can comprise one or more fans or other
gas propulsion mechanisms, such as to provide air or other gas to
inlet port assembly 21 (e.g. via the tube shown positioned between
controller 30 and inlet port assembly 21) or extract gas from
chamber 20 via outlet port assembly 22 (e.g. via the tube shown
positioned between controller 30 and outlet port assembly 22). In
some cases, controller 30 may comprise an alarm assembly, which can
be constructed and arranged to be activated when an undesired state
may be detected (e.g. an undesired concentration or amount of
solvent present, or other undesired state related to a solvent),
such as to notify an operator of system 10. Controller 30 can
comprise an alarm assembly constructed and arranged to provide an
alert selected from the group consisting of: audible alert; visual
alert; tactile alert; and any combination thereof. In some cases,
when an undesired state may be detected (e.g. an unacceptable
concentration of solvent within chamber 20, within conduit 120
and/or within covering 110 is detected), creation of covering 110
by system 10 may be stopped.
[0120] In some cases, system 10 may comprise one or more similar or
dissimilar spines 510, and graft device 100 may comprise one or
more of the spines 510. In some cases, material delivery device
(MDD) 300 may be configured to produce spine 510, such as when MDD
300 may comprise at least a 3D printer. System 10 can include spine
application tool 500, which can comprise a manual or automated
(e.g. robotic) tool used to place spine 510 about conduit 120, such
as between one or more layers of covering 110 (e.g. between an
inner layer with a first thickness, and an outer layer with a
second thickness about twice as thick as the first layer's
thickness). In some cases, system 10 can include one or more tools,
components, assemblies and/or otherwise be constructed and arranged
as described in applicant's co-pending U.S. patent application Ser.
No. 15/023,265, filed Mar. 18, 2016, the content of which is
incorporated herein by reference in its entirety for all
purposes.
[0121] In some cases, a system for producing a graft device may
comprise a tubular conduit; a first spine; and a fiber matrix
delivery assembly constructed and arranged to deliver a fiber
matrix to surround the tubular conduit.
[0122] In some cases, a system may comprise a second spine. The
first spine can comprise a first inner diameter and the second
spine can comprise a second inner diameter different than the first
inner diameter. The first inner diameter and the second inner
diameter can comprise approximate diameters selected from the group
consisting of: about 4.0 mm; about 4.7 mm and about 5.5 mm. The
system can comprise a third spine. The first spine can comprise a
first inner diameter, the second spine can comprise a second inner
diameter different than the first inner diameter, and the third
spine can comprise a third inner diameter different than the first
inner diameter and the second inner diameter. The first inner
diameter can comprise a diameter of about 4.0 mm, the second inner
diameter can comprise a diameter of about 4.7 mm and the third
inner diameter can comprise a diameter of about 5.5 mm.
[0123] In some cases, the system may comprise a spine application
tool constructed and arranged to apply a spine about the tubular
conduit. The spine application tool can be constructed and arranged
to laterally apply the spine about the tubular conduit. The fiber
matrix can comprise an inner layer and an outer layer, and the
spine application tool can be constructed and arranged to apply the
spine between the inner and outer layer of the fiber matrix. The
spine application tool can comprise an automated tool. The spine
application tool can comprise a robotic tool. The fiber matrix
delivery assembly can comprise the spine application tool. The
spine application tool can comprise a scissor-like
construction.
[0124] In some cases, the system may comprise a trimming tool
constructed and arranged to trim one or both ends of the spine. The
trimming tool can be constructed and arranged to trim the fiber
matrix. The trimming tool can comprise a tool selected from the
group consisting of: scissors; scalpel; laser cutter;
radiofrequency cutter; and any combination thereof. The fiber
matrix delivery assembly can comprise the trimming tool. The
trimming tool may comprise an automated tool. The trimming tool may
comprise a robotic tool. The fiber matrix delivery assembly can
comprise the trimming tool. The trimming tool can comprise a laser.
In some cases, the system may comprise a surface modifying
agent.
[0125] In some cases, the system may comprise a spine fabrication
tool constructed and arranged to produce the spine. The spine
fabrication tool can comprise a rod and a plurality of pins. The
rod can comprise a relatively linear rod. The rod can comprise at
least a non-linear portion. The fiber matrix delivery assembly can
comprise the spine fabrication tool. The fiber matrix delivery
assembly can comprise an el ectrospinning device constructed and
arranged to produce the spine. The fiber matrix delivery assembly
can comprise a three-dimensional printer constructed and arranged
to produce the spine. The fiber matrix delivery assembly can
comprise a stereolithography device constructed and arranged to
produce the spine. The fiber matrix delivery assembly may comprise
a fuse deposition device constructed and arranged to produce the
spine.
[0126] Also provided herein may be systems and methods for
producing a graft device commising a conduit, a surrounding fiber
matrix and a spine. Systems may include an el ectrospinning device
and/or other fiber or fiber matrix delivering assembly. In some
cases, the spine may comprise a component that may be applied,
placed andlor inserted, such as by the fiber matrix delivery
assembly (e.g. automatically or semi-automatically) or with a
placement or insertion tool (e.g. manually).
[0127] System can include a tool for applying spine about conduit,
such as spine application tool constructed and arranged to engage
an inner and/or outer portion of spine and subsequently cause spine
to radially expand to be placed (e.g. laterally placed) about
conduit. In some cases, tool can be constructed and arranged to
maintain the geometry (e.g. shape or alignment) of one or more
spines, such as to maintain the geometry of one or more spines
during shipping and/or storage.
[0128] System can include one or more agents for modifying the
surface of spine, conduit and/or a fiber matrix applied by fiber
matrix delivery assembly.
[0129] System can include one or more tools for cutting or
otherwise trimming one or more spines to a particular length, such
as trimming tool. Spine and one or more portions of an applied
fiber matrix can be trimmed prior to, during or after application
of one or more polymers from polymer solution dispenser by fiber
matrix delivery assembly. Trimming tool can be a manual tool and/or
an at least partially automated tool, such as a tool integrated
into fiber matrix delivery assembly. In some cases, a trimming tool
may comprise one or more cutting tools such as a cutting tool
selected from the group consisting of: scissors; scalpel; laser
cutter; radiofrequency cutter; and combinations thereof.
[0130] System can include one or more fasteners configured to apply
a retention force between at least two of tubular conduit, spine
and an applied fiber matrix comprising one or more polymers from
polymer solution dispenser. Fasteners can comprise one or more
elements selected from the group consisting; of: adhesive; staple;
clip; suture; barb; hook; and any combination thereof. In some
cases, fasteners comprise at least about 4 fasteners. In some
cases, one or more fasteners may be attached to and/or attachable
to spine. Fasteners can be applied to conduit and/or spine when
conduit and/or spine are positioned about mandrel. Fasteners can be
positioned within about 1 cm of one or both ends of conduit. In
some cases, one or more fasteners may comprise a material similar
to the material of spine, such as the material of an
interdigitating projection of spine as described herein.
[0131] System can include spine fabrication tool which may be
constructed and arranged to produce one or more spines. Spine
fabrication tool can be constructed and arranged to resiliently
bias spine, such as in a relatively linear or non-linear shape. In
some cases, a spine fabrication tool may be integral to fiber
matrix delivery assembly. In some cases, a fiber matrix delivery
assembly can create the spine with an assembly selected from the
group consisting of: an electrospinning device; a three-dimensional
printer; a stereolithography device; a fuse deposition device; and
any combination thereof. In some cases, a spine fabrication tool
may be a separate device. In some cases, a spine fabrication tool
may comprise one or more rods about which a filament is wrapped to
create spine, such as two or more rods with different outer
diameters used to produce two or more spines with different inner
diameters.
[0132] A system can include one or more patterning masks, such as a
physical or chemical mask used to prevent fiber matrix from
covering one or more portions of conduit. In some cases, a system
may include an aperture plate. Aperture plate can comprise a
stencil-like pattern configured to prevent or reduce delivery of
fiber to certain portions of the outer surface of conduit. In some
cases, an aperture plate can comprise a stencil-like pattern that
causes fiber matrix to include a pattern of relief slots. In some
cases, an aperture plate can be configured to induce one or more
changes to the electromagnetic (EM) field within electrospinning
device. These one or more changes to the EM field can be configured
to cause variations in the delivered fiber pathway, resulting in a
patterned fiber matrix. In some cases, a mandrel can have modified
electrical characteristics, such as modified conductivity along its
length, configured to modify the EM field to cause patterned fiber
deposition.
[0133] A system can include a power supply, power supply may be
configured to provide the electric potentials to nozzle and
mandrel, as well as to supply power to other components of system
such as drive assemblies and and modification assembly. Power
supply can be connected, either directly or indirectly, to at least
one of mandrel and conduit. Power can be transferred from power
supply to each component by, for example, one or more wires.
[0134] A system can include inlet and/or outlet ports. Ports may be
configured to control the environment surrounding the environment
surrounding mandrel. A port can be configured to be both an inlet
port and an outlet port. A system can include a housing. A housing
may be attachable to electrospinning device and defining a chamber
surrounding assemblies and/or and/or mandrel, such that the ports
can control a more limited (smaller) environment surrounding
assemblies and/or and/or mandrel. In some cases, the ports can be
used to introduce or remove one or more gases, introduce or remove
humidity, control temperature, control sterility, provide other
environmental controls, and any combination thereof.
[0135] Mandrel 320 can comprise a metal mandrel, such as a mandrel
constructed of 304 or 316 series stainless steel. Mandrel 320 can
comprise a mirror-like surface finish, such as a surface finish
with an R.sub.a of about 0.1 micrometers (.mu.m) to about 0.8
.mu.m. Mandrel 320 can comprise a length of up to about 45
centimeters (cm), such as a length of from about 30 cm to about 45
cm, or from about 38 cm to about 40 cm. In some cases, system 10
may include multiple mandrels 320 with multiple different
geometries, such as a set of mandrels 320 with different diameters
(e.g. diameters of about 3.0 millimeter (mm), about 3.5 mm, about
4.0 mm, and/or about 4.5 mm). In some cases, MDD 300 may be
configured to automatically detect the mandrel 320 diameter (e.g.
and to adjust rotation rate and/or another system parameter based
on the detected mandrel 320 diameter). One or both ends of mandrel
320 may be inserted into driving elements of rotating assembly 340,
motors 341a and 341b, respectively, such that mandrel 320 can be
rotated about axis 335 during creation of covering 110. In some
cases, a single motor may drive one end of mandrel 320, with the
opposite end attached to a rotatable attachment element (e.g. a
bearing) of MDD 300.
[0136] Mandrel 320 can comprise a porous mandrel, such as a mandrel
configured to deliver one or more drugs or other agents to covering
110 and/or conduit 120 prior to, during and/or after creation of
covering 110. In some cases, an agent 602 may be delivered to (e.g.
coated onto) covering 110 and/or conduit 120 via a porous mandrel
320, via material delivery assembly 305 (e.g. via nozzle 310), via
modification assembly 605 (e.g. via modifying element 627), or
otherwise. Agent 602 can comprise a solvent-reducing material (e.g.
a material configured to absorb solvent and a material configured
as a barrier that prevents solvent from reaching covering 110
and/or conduit 120), a solvent neutralizing material, a hydrating
solution and/or a preservative solution. In some cases, agent 602
may comprise a preservative solution comprising one or more
materials selected from the group consisting of: chilled fluid;
fluid chilled to about 4.degree. C.; water; saline; heparin;
heparinized saline; blood; ringers solution; and any combination
thereof. In some cases, agent 602 may comprise a material
configured as both a barrier and a solvent-absorbing material.
[0137] MDD 300 can include one or more material delivery
assemblies, and in the illustrated embodiment, MDD 300 may include
material delivery assembly 305. Material delivery assembly 305 may
comprise nozzle 310. Nozzle 310 may include an orifice constructed
and arranged to deliver material 350 to produce covering 110.
Nozzle 310 can be a tubular structure including nozzle central axis
328. Nozzle 310 can be constructed of stainless steel, such as
passivated 304 stainless steel. In some cases, nozzle 310 may
comprise an outer tube and an inner tube, such as to avoid icicle
formation about nozzle 310. For example, material delivery assembly
305 and/or nozzle 310 can be constructed and arranged as described
in applicant's co-pending application U.S. patent application Ser.
No. 15/036,304, filed May 12, 2016.
[0138] Electrospinning device can include one or more nozzle
assemblies. In some cases, an electrospinning device may include
nozzle assembly, which may include one or more nozzles. Nozzle
assembly may be fluidly attached to polymer solution dispenser via
delivery tube. Dispenser may comprise a solution of one or more
polymers, solvents and/or other materials. Nozzle assembly may be
operably attached to a linear drive assembly configured to
translate nozzle assembly in at least one direction.
[0139] In some cases, a modifying element may comprise a nozzle,
such as a nozzle configured to deliver a fiber modifying agent
and/or a graft modifying agent. A reference to a "nozzle" and
"nozzle assembly" in singular or plural form can include one or
more nozzles, such as nozzle, and one or more assemblies, such as
nozzle assemblies.
[0140] Nozzle can be constructed of stainless steel. In some cases,
nozzle may have a tubular construction with a length of about 1.5
inches, an inner diameter (ID) of about 0.047 inches and an outer
diameter (OD) of about 0.065 inches. Nozzle can include an
insulating coating, with the tip of nozzle exposed (e.g.
non-insulated), such as with an exposed length of about 1
centimeter (cm). Nozzle geometry and electrical potential voltages
applied between nozzle and mandrel may be chosen to control fiber
generation. In some cases, fibers may be produced with an average
diameter from about 1.0 micrometer (.mu.m) to about 20 .mu.m, such
as from about 5 .mu.m to about 15 .mu.m, or from about 6 .mu.m to
about 12 .mu.m.
[0141] A mandrel may be positioned in a particular spaced
relationship from nozzle assembly and/or modification assembly, and
nozzle and/or modifying element, respectively. In some cases, a
mandrel may be positioned above and below assemblies and,
respectively. In some cases, a mandrel can be positioned either
above, below, to the right and/or or to the left of, assembly
and/or assembly. The distance between mandrel and the tip of nozzle
and/or modifying element can be less than about 20 cm, or less than
about 15 cm. In some cases, the tip of nozzle and/or modifying
element may be about 12.5 cm from mandrel. In some cases, multiple
nozzles and/or multiple modifying elements, for example components
of similar or dissimilar configurations, can be positioned in
various orientations relative to mandrel. In some cases, the
distance between nozzles and/or modifying elements and mandrel may
vary along the length of mandrel, such as to create a varying
pattern of fiber matrix along conduit. In some cases, a nozzle
and/or modifying element distances from mandrel can vary
continuously during the electrospinning process and/or the distance
can vary for one or more set periods of time during the
process.
[0142] In some cases, an electrical potential may be applied
between nozzle and one or both of conduit and mandrel. The
electrical potential can draw at least one fiber from nozzle
assembly to conduit. Conduit can act as the substrate for the
electrospinning process, collecting the fibers that may be drawn
from nozzle assembly by the electrical potential. In some cases, a
mandrel and/or conduit may have a lower voltage than a nozzle to
create the desired electrical potential.
[0143] In some cases, a polymer solution, stored in polymer
solution dispenser, may be delivered to nozzle assembly through
polymer solution delivery tube. The electrical potential between
nozzle and conduit and/or mandrel can draw the polymer solution
through nozzle of nozzle assembly. Electrostatic repulsion that may
be caused by the fluid becoming charged from the electrical
potential, may counteract the surface tension of a stream of the
polymer solution at nozzle of the nozzle assembly. After the stream
of polymer solution may be stretched to its critical point, one or
more streams of polymer solution may emerge from nozzle of nozzle
assembly, and/or at a location below nozzle assembly, and may move
toward the negatively charged conduit. Using a volatile solvent,
the solution may dry substantially during transit and the fiber may
be deposited on conduit.
[0144] Material delivery assembly 305 may be fluidly attached to
material dispenser 301 via delivery tube 325. Material delivery
assembly 305 may receive material 350 and may deliver material 350
to produce covering 110 (e.g. delivers material 350 to mandrel 320
and/or conduit 120). Material delivery assembly 305 can comprise
one or more pumping mechanisms, such as a syringe pump (e.g. a
syringe pump in which material 350 is contained within the
syringe), a peristaltic pump, a displacement pump and/or other
pumping mechanism. Material delivery assembly 305 can comprise
linear drive assembly 345. Linear drive assembly 345 may translate
nozzle 310 in at least one direction for a linear travel distance
D.sub.SWEEP as shown. In some cases, linear drive assembly 345 may
reciprocally translate nozzle 310 along the distance D.sub.SWEEP.
In some cases, D.sub.SWEEP may comprise a length of about 30
centimeters (cm), such as a length of at least about 10 cm, about
20 cm, about 30 cm, about 35 cm, or about 40 cm. In some cases,
linear drive assembly 345 may move nozzle 310 based on a
construction signal 201 produced by processing unit 200, such as a
construction signal 201 based on image data of conduit 120 produced
by imaging device 400.
[0145] As described herein, mandrel 320 can be rotated about axis
335 during the delivery of material 350 by material delivery
assembly 305 to produce covering 110. In some cases, material
delivery assembly 305 (e.g. and nozzle 310) can rotate about
mandrel 320 during delivery of material 350 (e.g. as material
delivery assembly 305 and mandrel 320 may translate relative to
each other via translational motion of either or both).
[0146] In some cases, material 350 may comprise two or more
polymers, such as a first polymer with a first hardness, and a
second polymer with a second hardness different than the first
hardness. Material 350 can comprise a mixture of similar or
dissimilar amounts of polyhexamethylene oxide soft segments, and
aromatic methylene diphenyl isocyanate hard segments. Material 350
can comprise one or more solvents, such as hexafluoro-2-propanol
(HFIP) (e.g. HFIP with an about 99.97% minimum purity). Material
350 can comprise one or more polymers in a concentrated solution
fully or at least partially solubilized within a solvent and
comprise a polymer weight to solvent volume ratio from about 20% to
about 35%, where a concentration may be from about 24% to about 26%
(more specifically from about 24.5% to about 25.5%). Material 350
can comprise one or more materials with a molecular weight average
(Mw) from about 80,000 to about 150,000 (polydispersity index
(PDI)--molecular weight per molecular number (Mw/Mn) from about 2.1
to about 3.5). Material 350 can comprise a solution with a
viscosity from about 2000 centipoise (cP) to about 2400 cP
(measured at about 25.degree. C. and with shear rate equal to about
20 s.sup.-1). Material 350 can comprise a solution with a
conductivity from about 0.4 microSiemens per centimeter (.mu.S/cm)
to about 1.7 .mu.S/cm (measured at a temperature from about
20.degree. C. to about 22.degree. C.). Material 350 can comprise a
solution with a surface tension from about 21.5 milliNewtons per
meter (mN/m) to about 23.0 mN/m (measured at about 25.degree.
C.).
[0147] In some cases, system 10 may be constructed and arranged to
produce a covering 110 with a thickness (absent of any spine 510)
of from about 220 .mu.m to about 280 .mu.m. Covering 110 can
comprise a matrix of fibers with a diameter from about 6 .mu.m to
about 15 .mu.m, such as a matrix of fibers with an average diameter
of from about 7.8 .mu.m to about 8.6 .mu.m. Covering 110 can
comprise a porosity of from about 0% to about 99%, such as from
about 30% to about 80%, from about 40% to about 80%, or from about
50% to about 70%. In some cases, covering 110 may comprise an
average compliance ("compliance" herein) from about
0.2.times.10.sup.-4/millimeter of mercury (mmHg) to about
3.0.times.10.sup.-4/mmHg when measured in arterial pressure ranges.
In some cases, covering 110 may comprise an elastic modulus from
about 10 MPa to about 18 MPa.
[0148] Material delivery assembly 305 can be configured to deliver
material 350 to nozzle 310 at a flow rate of from about 10
milliliters per hour (ml/hr) to about 25 ml/hr, such as at a flow
rate of from about 15 ml/hr to about 20 ml/hr, such as about 15
ml/hr or about 20 ml/hr.
[0149] As described above, in some cases, system 10 may be
constructed and arranged to produce a graft device 100 including a
spine 510. Spine 510 can comprise multiple spines 510 with
different inner diameters (IDs), such as multiple spines with IDs
of about 4.0 millimeters (mm), about 4.7 mm, and/or about 5.5 mm.
Spine 510 can comprise a filament 516 with a diameter of about 0.4
mm (e.g. for a spine with an ID from about 4.0 mm to about 4.7 mm).
Spine 510 can comprise a filament 516 with a diameter of about 0.5
mm (e.g. for a spine with an ID from about 4.8 mm to about 5.5 mm).
Spine 510 can comprise a series of inter-digitating fingers spaced
about 0.125 inches from each other so that the recurring unit of
spine including one left finger and one right finger occurs about
every 0.25 inches. This recurring feature length can have a range
comprised from about 0.125 inches to about 0.375 inches. The
fingers can overlap in a symmetric or asymmetric pattern, such as
an overlap of opposing fingers from about 2.5 mm to about 1.0 mm
around the circumferential perimeter of spine 510. Spine 510 can be
heat treated to achieve a resilient bias. Spine 510 can be
surface-treated (e.g. with dimethylformamide) to increase the
surface roughness and reduce crystallinity (e.g. to improve
solvent-based adhesion with the covering 110).
[0150] Spine 510 can include one or more portions that may be
resiliently biased, such as a resilient bias may be configured to
provide a radial outward force at locations proximate ends 101
and/or 102, such as to provide a radial outward force to support or
enhance the creation of an anastomosis during a cardiovascular
bypass procedure. In some cases, spine 510 may include one or more
portions that are malleable.
[0151] Spine 510 can include multiple curved projections 511' and
511'', collectively 511. One or more projections 511' (such as each
projection) may include a tip portion 512' and one or more
projections 511'' (such as each projection) may include a tip
portion 512'' (collectively, tip portions 512). Tip portions 512
can be arranged in the overlapping arrangement shown in FIG. 3.
Projections 511' and 511'' can comprise a first and second support
portion, respectively, that are arranged such that at least one
rotates relative to the other to create an opening to receive
conduit 120. In some cases, one or more tip portions 512 (such as
each tip portion) can comprise a diameter from about 0.020 inches
to about 0.064 inches, such as a diameter about 0.042 inches. One
or more projections 511 (such as each projection) can comprise a
loop of a filament (e.g. a loop of a continuous filament), and
projections 511' and 511'' can be arranged in an interdigitating
arrangement such as the alternating, interdigitating arrangement
shown in FIG. 3. In some cases, the interdigitating projections
511' and 511'' can overlap (e.g. spine 510 covers more than
360.degree. of conduit 120). In some cases, projections 511' and
511'' may be arranged with an overlap of at least about 1.0
millimeters (mm), at least about 1.1 mm or at least about 1.4 mm.
In some cases, spine 510 can be constructed and arranged as
described in applicant's co-pending U.S. patent application Ser.
No. 15/023,265, filed Mar. 18, 2016, the content of which is
incorporated herein by reference in its entirety for all
purposes.
[0152] A graft device can include a spine, such as to prevent
luminal narrowing, radial collapse, kinking and/or other undesired
movement of the graft device (e.g. movement into an undesired
geometric configuration), such as while implanting the graft device
during a surgical procedure and/or at a time after implantation.
The spine can be placed inside the tubular conduit, between the
tubular conduit and the fiber matrix, between layers or within
layers of the fiber matrix and/or outside the fiber matrix. The
spine can comprise a biodegradable or bioerodible (hereinafter
"biodegradable") material or otherwise be configured to provide a
temporary support to the graft device. In some cases, a spine can
comprise one or more portions including durable or otherwise
non-biodegradable materials configured to remain intact for long
periods of time when implanted, such as at least about 6 months or
at least about 1 year.
[0153] Also provided herein are systems and methods for producing a
graft device comprising a conduit, a surrounding fiber matrix and a
spine. Systems may include an electrospinning device and/or other
fiber or fiber matrix delivering assembly. In some cases, the spine
may comprise a component that may be applied, placed and/or
inserted, such as by the fiber matrix delivery assembly (e.g.
automatically or semi-automatically) or with a placement or
insertion tool (e.g. manually).
[0154] Graft device can include spine. Spine may be constructed and
arranged to prevent graft device from undergoing undesired motion
such as kinking or other narrowing, such as during implantation
procedure and/or while under stresses endured during its functional
lifespan. In some cases, spine may surround conduit, positioned
between conduit and fiber matrix, where spine may comprise a
diameter approximating the outer diameter of conduit. In some
cases, spine, in whole or in part, can be between one or more
layers of fiber matrix. In some cases, spine, in whole or in part,
can surround fiber matrix. In some cases, spine may be positioned
within conduit. In some cases, multiple spines can be included,
each surrounding tubular conduit, surrounding fiber matrix and/or
positioned between two or more layers of fiber matrix.
[0155] Spine can be constructed and arranged to provide one or more
functions selected from the group consisting of: minimizing
undesirable conditions, such as buckling, conduit deformation,
luminal deformation, stasis, flows characterized by significant
secondary components of velocity vectors such as vortical,
recirculating or turbulent flows, luminal collapse, and/or thrombus
formation; preserving laminar flow such as preserving laminar flow
with minimal secondary components of velocity, such as blood flow
through graft device, blood flow proximal to graft device and/or
blood flow distal to graft device; preventing bending and/or
allowing proper bending of the graft device, such as bending that
occurs during and/or after the implantation procedure; preventing
accumulation of debris; preventing stress concentration on the
tubular wall; maintaining a defined geometry in tubular conduit;
preventing axial rotation about the length of tubular conduit; and
combinations thereof. Spine and fiber matrix can comprise similar
elastic moduli, such as to avoid dislocations and/or separations
between the two components over time, such as when graft device
undergoes cyclic motion and/or strain.
[0156] Spine can be applied around conduit prior to, during and/or
after application of fiber matrix to graft device. For example,
spine can be applied prior to application of fiber matrix when
spine may be positioned between conduit and fiber matrix. Spine can
be applied during application of fiber matrix when spine may be
positioned between one or more layers of fiber matrix. Spine can be
applied after application of fiber matrix when spine may be
positioned outside of fiber matrix. Spine can be applied about
conduit and/or at least a layer of fiber matrix with one or more
tools.
[0157] Spine can include one or more portions that are resiliently
biased, such as a resilient bias configured to provide a radial
outward force at locations proximate ends and/or, such as to
provide a radial outward force to support or enhance the creation
of an anastomosis as described herein. Spine can include one or
more portions that are malleable.
[0158] In some cases, a spine may include multiple curved
projections and, singly or collectively projections. One or more
projections, such as each projection may include a tip portion
(singly or collectively, tip portions). In some cases, one or more
tip portions or each tip portion can comprise a diameter from about
0.020 inches to about 0.064 inches, such as a diameter of about
0.042 inches. One or more projections or each projection can
comprise a loop of a filament (e.g. a loop of a continuous
filament), and projections and can be arranged in an
interdigitating arrangement such as the alternating,
interdigitating arrangement. In some cases, the interdigitating
projections and can overlap (e.g. spine covers more than
360.degree. of conduit). In some cases, projections can be arranged
with an overlap of at least about 1.0 mm, at least about 1.1 mm or
at least about 1.4 mm. A set of projections can comprise first
support portion, whose tip portions can be collectively deflected
or otherwise rotated towards the top of the page. A set of
projections can comprise a second support portion, whose tip
portions can be collectively deflected or otherwise rotated towards
the bottom of the page. The rotations of first support portion and
second support portion may create an opening that may allow a spine
to approach and surround conduit from the side (e.g. laterally
engage conduit and/or at least a layer of fiber matrix already
applied to conduit). Rotation of first support portion relative to
second support portion and/or rotation of second support portion
relative to first support portion can be performed with one or more
spine application tools.
[0159] A spine can comprise at least three projections, such as at
least six projections. In sonic cases, a spine may include at least
two projections for every about 15 mm of length of spine, such as
at least two projections for every about 7.5 mm of length of spine,
or at least two projections for every about 2 mm of length of
spine. In some cases, spine comprises two projections for each
about 6.5 mm of length of spine.
[0160] A spine can comprise one or more continuous filaments, such
as three or less continuous filaments, two or less continuous
filaments, or a single continuous filament. In some cases, spine
may comprise a continuous filament of at least about 15 inches
long, or at least about 30 inches long such as when spine comprises
a length of about 3.5 inches. In some cases, filament may comprise
a length (e.g. a continuous length or a sum of segments with a
cumulative length) of about 65 inches (e.g. to create a 4.0 mm
diameter spine), or a length of about 75 inches (e.g. to create a
4.7 mm diameter spine), or a length of about 85 inches (e.g. to
create a 5.5 mm diameter and/or 3.5 inches long spine). A filament
can comprise a relatively continuous cross section, such as an
extruded or molded filament with a relatively continuous cross
section. Spine can comprise a filament including at least a portion
with a cross section with a geometry selected from the group
consisting of: elliptical; circular; oval; square; rectangular;
trapezoidal; parallelogram-shaped; rhomboid-shaped; T-shaped;
star-shaped; spiral-shaped; (e.g. a filament comprising a rolled
sheet); and any combination thereof. A filament can comprise a
cross section with a major axis from about 0.2 mm to about 1.5 mm
in length, such as a circle or oval with a major axis less than or
equal to about 1.5 mm, less than or equal to about 0.8 mm, or less
than or equal to about 0.6 mm, or from about 0.4 mm to about 0.5
mm. Filament can comprise a cross section with a major axis greater
than or equal to about 0.1 mm, such as a major axis greater than or
equal to about 0.3 mm. In sonic cases, the major axis and/or cross
sectional area of filament may be proportionally based to the
diameter of spine (e.g. a larger spine diameter correlates to a
larger filament diameter, such as when a range of different
diameter spine are provided in a kit.
[0161] A spine can comprise a tubular structure, such as a full
circumferential (e.g. at least) 360.degree. or partial
circumferential tubular structure. In some cases, a spine may
comprise an inner diameter D.sub.S that may approximate the outer
diameter of tubular conduit, diameter D.sub.TC. In some cases,
spine may comprise an inner diameter D.sub.S that may approximate
the outer diameter of a partial layer of fiber matrix covering
tubular conduit. In some cases, a spine may comprise an inner
diameter D.sub.S that may approximate the outer diameter of a full
layer of fiber matrix covering tubular conduit. A spine can
comprise an inner diameter of at least about 2 mm or an inner
diameter of no more than about 20 mm. A spine can comprise a length
from about 2 inches to about 6 inches, such as a length from about
3 inches to about 5 inches. In some cases, a spine may comprise
multiple tubular structures with lengths from about 1 inches to
about 4 inches.
[0162] A spine can comprise a material with a durometer from about
52 D to about 120 R, such as from about 52 D to about 85 D, such as
from about 52 D to about 62 D. In some cases, a spine may comprise
a material with a durometer of about 55 D. A spine can comprise one
or more polymers, such as a polymer selected from the group
consisting of: silicone; polyether block amide; polypropylene;
nylon; polytetrafluoroethylene; polyethylene; ultra high molecular
weight polyethylene; polycarbonates; polyolefins; polyurethanes;
polyvinylchlorides; polyamides; polyimides; polyacrylates;
polyphenolics; polystyrene; polycaprolactone; polylactic acid;
polyglycolic acid; polyglycerol sebacate; hyaluric acid; silk
fibroin collagen; elastin; poly(p-dioxanone);
poly(3-hydroxybutyrate); poly(3-hydroxyvalerate);
poly(valcrolactone); poly(tartronic acid); poly(beta-malonic acid);
poly(propylene fumarates); a polyanhydride; a tyrosine-derived
polycarbonate; a polyorthoester; a degradable polyurethane; a
polyphosphazene; and any combination thereof. A spine can comprise
the same material as fiber matrix, such as when both may comprise
the same electrospun material.
[0163] A spine can comprise at least one thermoplastic co-polymer.
A spine can comprise two or more materials, such as a first
material and a second material harder than the first material. In
some cases, a spine can comprise relatively equal amounts of a
harder material and a softer material. The softer material can
comprise polydimethylsiloxane and a polyether-based polyurethane
and the harder material can comprise aromatic methylene diphenyl
isocyanate. A spine can comprise one or more drugs or other agents,
such as one or more agents constructed and arranged to be released
over time.
[0164] In some cases, a spine may comprise a metal material, such
as a metal selected from the group consisting of: nickel titanium
alloy; titanium alloy; titanium; stainless steel; tantalum;
magnesium; cobalt-chromium alloy; gold; platinum; and combinations
thereof. In some cases, a spine may comprise a reinforced resin,
such as a resin reinforced with carbon fiber and/or Kevlar. In some
cases, at least a portion of a spine may be biodegradable, such as
when a spine may comprise a biodegradable material such as a
biodegradable metal or biodegradable polymer. In some cases, fiber
matrix can comprise a biodegradable material and/or a
non-biodegradable material. In some cases, a spine may not comprise
a biodegradable material. In some cases, fiber matrix can comprise
a biodegradable material and/or a non-biodegradable material.
[0165] A spine can be configured to biodegrade over time such as to
provide a temporary kink resistance or other function to device. In
some cases, a spine can temporarily provide kink resistance to
graft device for a period of less than about twenty-four hours. In
some cases, a spine can provide kink resistance to graft device for
a period of less than about one month. In some cases, a spine can
provide kink resistance to graft device for a period of less than
about six months.
[0166] A spine can comprise a polymer constructed and arranged to
change one or more properties upon exposure to an external stimuli.
The polymer can comprise a polymer selected from the group
consisting of: N-isopropylacrylamide (NIPAAm); a polaxamer
(Pluronics); and any combination thereof. The external stimuli can
comprise a stimuli selected from the group consisting of:
temperature; pH; light; magnetic field; electric field; exposure to
a solvent; and any combination thereof. The changed property can
comprise a property selected from the group consisting of:
hydrophobicity; a material property; an adhesive property; size;
geometry; and combinations thereof. For instance, spine can exhibit
an increase of hydrophobicity when exposed to a stimuli such as an
electromagnetic field, such as an electromagnetic field that may be
provided during an electrospinning process as described herein.
[0167] A spine can comprise one or more coatings. A coating can
cover all or a portion of one or more filaments. A spine can
comprise an inner surface and an outer surface, and coating can be
positioned on inner surface, on outer surface, and/or on another
surface of spine. A coating can comprise an adhesive element or
otherwise exhibit adhesive properties, such as a coating comprising
a material selected from the group consisting of: fibrin gel;
starch-based compound; mussel adhesive protein; and any combination
thereof. A coating can be constructed and arranged to provide a
function selected from the group consisting of:
anti-thrombogenecity; anti-proliferation; anti-calcification;
vasorelaxati on; and any combination thereof. A coating can
comprise a dehydrated gelatin, such as a dehydrated gelatin coating
configured to hydrate to cause adherence of spine to conduit. A
coating can comprise a hydrophilic and/or a hydrophobic coating. A
coating can comprise a radiopaque coating. in some cases, a spine
may comprise at least a portion that may be radiopaque, such as
when spine may comprise a radiopaque material such as barium
sulfate.
[0168] A spine can be constructed and arranged to be cut to length
during the manufacturing process, such as at a time after
application of at least a portion of fiber matrix. A spine can be
cut with one or more tools, such as trimming tool.
[0169] Spine 510 can comprise at least three projections 511, such
as at least six projections 511. In some cases, spine 510 may
include at least two projections 511 for every about 15 mm of
length of spine 510, such as at least about two projections 511 for
every about 7.5 mm of length of spine 510, or at least about two
projections for every about 2 mm of length of spine 510. In some
cases, spine 510 may comprise about two projections 511 for each
about 6.5 mm of length of spine 510. In some cases, a series of
projections 511 may be positioned about 0.125 inches from each
other.
[0170] Spine 510 can comprise one or more continuous filaments 516,
such as three or less continuous filaments, two or less continuous
filaments, or a single continuous filament. In some cases, spine
510 may comprise a continuous filament 516 of at least about 15
inches long (i.e. the curvilinear length), or at least about 30
inches long, such as when spine 510 comprises a length of about 3.5
inches. In some cases, filament 516 may comprise a length (e.g. a
continuous curvilinear length or a sum of segments with a
cumulative curvilinear length) of about 65 inches (e.g. to produce
an about 4.0 mm diameter spine 510), or a length of about 75 inches
(e.g. to produce an about 4.7 mm diameter spine 510), or a length
of about 85 inches (e.g. to produce an about 5.5 mm diameter spine
510). Filament 516 can comprise a relatively continuous cross
section, such as an extruded or molded filament with a relatively
continuous cross section. Spine 510 can comprise a filament 516
including at least a portion with a cross sectional geometry
selected from the group consisting of: elliptical; circular; oval;
square; rectangular; trapezoidal; parallelogram-shaped;
rhomboid-shaped; T-shaped; star-shaped; spiral-shaped; (e.g. a
filament comprising a rolled sheet); and any combination thereof or
other geometries. Filament 516 can comprise a cross section with a
major axis from about 0.2 mm to about 1.5 mm in length, such as a
circle or oval with a major axis less than or equal to about 1.5
mm, less than or equal to about 0.8 mm, or less than or equal to
about 0.6 mm, or from about 0.4 mm to about 0.5 mm. Filament 516
can comprise a cross section with a major axis greater than or
equal to about 0.1 mm, such as a major axis greater than or equal
to about 0.3 mm. In some cases, the major axis and/or cross
sectional area of filament 516 may be proportionally based to the
diameter of spine 510 (e.g. a larger spine 510 diameter may
correlate to a larger filament 516 diameter, such as when a range
of different diameter spine 510's may be provided in a kit).
[0171] Filament 516 can be a single core, monofilament structure.
In some cases, filament 516 can comprise multiple filaments, such
as a braided multiple filament structure. In some cases, filament
516 can comprise an injection molded component or a thermoset
plastic component, such as when spine 510 comprises multiple
projections 511 that may be produced at the same time as the
creation of one or more filaments 516 (e.g. when filament 516 may
be created in a three-dimensional biased shape).
[0172] Filament 516 can comprise a 3D printed component, an
extruded component, a molded component, and/or an electrospun
component, such as a component produced by the same device used to
produce covering 110 (e.g. MDD 300), such as when spine 510 and
covering 110 may comprise the same or similar materials.
[0173] Spine 510 can comprise a material with a durometer from
about 40D to about 120R, such as from about 50D to about 85D, such
as from about 52D to about 62D. In some cases, spine 510 may
comprise a material with a durometer of about 55D. Spine 510 can
comprise one or more polymers, such as a polymer selected from the
group consisting of: silicone; polyether block amide;
polypropylene; nylon; polytetrafluoroethylene; polyethylene;
ultra-high molecular weight polyethylene; polycarbonates;
polyolefins; polyurethanes; polyvinylchlorides; polyamides;
polyimides; polyacrylates; polyphenolics; polystyrene;
polycaprolactone; polylactic acid; polyglycolic acid; polyglycerol
sebacate; hyaluronic acid; silk fibroin collagen; elastin;
poly(p-dioxanone); poly(3-hydroxybutyrate);
poly(3-hydroxyvalerate); poly(valecrolactone); poly(tartronic
acid); poly(beta-malonic acid); poly(propylene fumarates); a
polyanhydride; a tyrosine-derived polycarbonate; a polyorthoester;
a degradable polyurethane; a polyphosphazene; and any combination
thereof or other materials.
[0174] Spine 510 can comprise the same or substantially similar
material(s) as covering 110. Spine 510 can comprise at least one
thermoplastic co-polymer. Spine 510 can comprise two or more
materials, such as a first material and a second material harder
than the first material. In some cases, spine 510 may comprise
relatively equal amounts of a harder material and a softer
material. The softer material can comprise polydimethylsiloxane and
a polyether-based polyurethane, and the harder material can
comprise aromatic methylene diphenyl isocyanate. Spine 510 can
comprise one or more drugs or other agents, such as one or more
agents constructed and arranged to be released over time.
[0175] In some cases, spine 510 may comprise a metal material, such
as a metal selected from the group consisting of: a nickel titanium
alloy; a titanium alloy; titanium; stainless steel; tantalum;
magnesium; cobalt-chromium alloy; gold; platinum; and any
combination thereof or other materials. In some cases, spine 510
may comprise a reinforced resin, such as a resin reinforced with
carbon fiber and/or Kevlar. In some cases, at least a portion of
spine 510 may be biodegradable, such as when spine 510 may comprise
a biodegradable material such as a biodegradable metal or
biodegradable polymer. In some cases, covering 110 can comprise a
non-biodegradable material. In some cases, spine 510 may not
comprise a biodegradable material.
[0176] Spine 510 can be configured to biodegrade over time such as
to provide a temporary kink resistance or other function to graft
device 100. In one embodiment, spine 510 can temporarily provide
kink resistance to graft device 100 for a period of less than about
twenty-four hours. In an alternative embodiment, spine 510 can
provide kink resistance to graft device 100 for a period of less
than about one month. In yet another embodiment, spine 510 can
provide kink resistance to graft device 100 for a period of less
than about six months. Numerous forms of biodegradable materials
can be employed. Bolz et al. (U.S. Pat. No. 6,287,332) discloses a
biodegradable implant which may include a combination of metal
materials that can be an alloy or a local galvanic element. Metal
alloys can consist of at least a first component which forms a
protecting passivation coat and a second component configured to
ensure sufficient corrosion of the alloy. The first component may
be at least one component selected from the group consisting of:
magnesium, titanium, zirconium, niobium, tantalum, zinc and
silicon, and the second component is at least one metal selected
from the group consisting of: lithium, sodium, potassium,
manganese, calcium and iron. Furst et al. (U.S. patent application
Ser. No. 11/368,298) discloses an implantable device at least
partially formed of a bioabsorbable metal alloy that includes a
majority weight percent of magnesium and at least one metal
selected from calcium, a rare earth metal, yttrium, zinc and/or
zirconium. Doty et al. (U.S. patent application Ser. No.
11/744,977) discloses a bioabsorbable magnesium reinforced polymer
stent that includes magnesium or magnesium alloys. Numerous
biodegradable polymers can be used such as are described
herein.
[0177] System 10 can include drying assembly 650, which can be
constructed and arranged to remove moisture or other fluids from
conduit 120 and/or covering 110, such as to remove solvent from
locations surrounding conduit 120 and/or covering 110. Drying
assembly 650 can comprise a heat generator, dehydrator, desiccant
or other fluid absorbing material, and/or other mechanism may be
configured to remove solvent from locations on, within, and/or
proximate conduit 120 and/or covering 110. Drying assembly 650 can
comprise a handheld device. In some cases, conduit 120 may comprise
harvested tissue (e.g. a harvested saphenous vein segment) and
drying assembly 650 may comprise gauze or other material used to
manually remove fluids from conduit 120, such as to remove solvents
and/or improve adherence between covering 110 and conduit 120.
[0178] MDD 300 can include one or more modification assemblies
constructed and arranged to modify one or more components and/or
one or more portions of graft device 100. In the illustrated
embodiment, MDD 300 may include modification assembly 605.
Modification assembly 605 may comprise a nozzle assembly or other
modifying element, modifying element 627. Modification assembly 605
may comprise linear drive assembly 645. Assembly 605 may be
operably attached to linear drive assembly 645, which may be
configured to translate assembly 605 in at least one direction,
such as a reciprocating motion in back and forth directions
spanning a distance similar to D.sub.SWEEP of linear drive assembly
345. Assembly 605 can be operably attached to supply 620 via
delivery tube 625.
[0179] Modification assembly 605 can be configured to remove vapor
from about conduit 120 and/or covering 110, such as to reduce the
amount of solvent in conduit 120 and/or covering 110. In some
cases, supply 620 can comprise a vacuum that enables modifying
element 627 (e.g. a nozzle) to extract gas and/or vapor via
delivery tube 625.
[0180] System 10 can include one or more graft device 100 modifying
agents, such as agent 602 shown. Agent 602 can comprise a solvent
configured to perform a surface modification, such as a solvent
selected from the group consisting of: dimethylformamide;
hexafluoroisopropanol; tetrahydrofuran; dimethyl sulfoxide;
isopropyl alcohol; ethanol; and any combination thereof or other
solvents. In some cases, system 10 may be constructed and arranged
to perform a surface modification configured to enhance the
adhesion of two or more of: conduit 120, spine 510 and covering
110. In some cases, system 10 may be constructed and arranged to
perform a surface modification to covering 110 and/or spine 510 to
cause a modification of the surface energy of covering 110 and/or
spine 510, respectively. In some cases, the surface of spine 510
may be modified with a heated die comprising a textured or
otherwise non-uniform surface. In some cases, MDD 300 and/or
another component of system 10 may comprise a radiofrequency plasma
glow discharge assembly constructed and arranged to perform a
surface modification of spine 510, such as a process performed in
the presence of a material selected from the group consisting of:
hydrogen; nitrogen; ammonia; oxygen; carbon dioxide; C2F6; C2F4;
C3F6; C2H4; CH4; and any combination thereof or other
materials.
[0181] Supply 620 can comprise one or more of: a reservoir of one
or more agents, such as agent 602; a power supply such as a laser
power supply; and/or a reservoir of compressed fluid. In some
cases, modifying element 627 may comprise a nozzle, such as a
nozzle configured to deliver a covering 110 modifying agent, a
conduit 120 modifying agent, a spine 510 modifying agent, and/or a
graft device 100 modifying agent.
[0182] For clarification, any reference to a "nozzle" or
"assembly", in singular or plural form, can include one or more
nozzles, such as one or more nozzles 310 or one or more modifying
elements 627 configured as a nozzle, or one or more assemblies,
such as one or more material delivery assemblies 305 or one or more
modification assemblies 605.
[0183] In some cases, modifying element 627 may be configured to
deliver agent 602. For example, agent 602 can comprise a wax, gel
(e.g. a pluronic gel or other poloxamer gel) or other protective
material delivered to conduit 120 prior to the application of
covering 110 to conduit 120, the delivered agent 602 may be
configured to protect conduit 120 from adverse effects of covering
110 (e.g. protection from one or more solvents or other potentially
harmful materials of covering 110). In some cases, agent 602 can
comprise a neutralizing material (e.g. a material configured to
neutralize adverse effects of potentially harmful materials), the
agent 602 may be delivered to conduit 120 prior to and/or during
the application of covering 110 to conduit 120. This delivery of
agent 602 can be performed to prevent or otherwise minimize
exposure of conduit 120 to one or more solvents (e.g.
hexafluoro-2-propanol (HFIP)) may be included in material 350,
and/or to reduce injury to conduit 120 by any solvent.
[0184] An agent 602 comprising a solvent-reducing material and/or a
solvent neutralizing material can be delivered via mandrel 320
(e.g. when mandrel 320 comprises a porous mandrel), via modifying
element 627, and/or via a separate device. Agent 602 can be applied
to one or more surfaces of conduit 120 via a method selected from
the group consisting of: spraying; dipping; dripping; brushing, and
any combination thereof. Agent 602 can be applied to conduit 120
prior to and/or after placing conduit 120 around mandrel 320. In
some cases, agent 602 may comprise a solvent-reducing material
comprising a thermogelling fluid, such as pluronic 407 poloxamer
gel, or an equivalent, configured as a barrier. An agent 602
comprising a thermogel can be applied at a temperature below the
solution gelation temperature such that the solution is a liquid
during application and gels on a surface of conduit 120. In some
cases, the thermogel can be gelled prior to application onto
conduit 120. In some cases, an agent 602 comprising a gel or other
material may be applied at a thickness from about 0.1 mm to about 2
mm to one or more surfaces (e.g. the entire outer surface or a
portion thereof such as a majority of the outer surface) of conduit
120.
[0185] Agent 602 can comprise a thermogel solution prepared using
distilled or ionized water, or the thermogel can be prepared using
a preservative solution (e.g. to increase the buffering capacity of
the thermogel). Examples of applicable preservative solutions may
include but are not limited to: phosphate buffered saline (PBS);
cell culture media (e.g. Dulbecco's Modified Eagle Media or Gibco
RPMI 1640); balanced salt solution (e.g. lactated ringer's solution
or Hank's Balanced Salt solution); and/or a cardioplegia solution.
Agent 602 can comprise one or more materials added to a thermogel
solution, such as to perform a function selected from the group
consisting of: increase buffering capacity of the solution; modify
the pH of the solution; act as a solvent scavenger (e.g. an HFIP
scavenger); and any combination thereof. For example, agent 602 can
comprise: a salt (e.g. a sodium or potassium salt); sodium
bicarbonate; powdered cell culture media; uridine diphosphate
glucuronic acid; and any combination thereof. Following application
of covering 110 onto conduit 120, agent 602 can be left in place
during implantation of graft device 100. In some cases, graft
device 100 can be placed in a solution (e.g. a cooled vein
preservation solution), to re-liquefy agent 602 (e.g. re-liquefy a
thermogel material component of agent 602) such that it can be
removed from graft device 100.
[0186] Application of agent 602 (e.g. a poloxamer gel) onto a
surface (e.g. the outer surface) of conduit 120 as a temporary
layer between covering 110 and conduit 120 may provide numerous
advantages. In some cases, agent 602 comprising a gel or other
material can provide an adhesive connection between conduit 120 and
covering 110, such as to improve post-application handling of
conduit 120. In some cases, agent 602 may be applied as a temporary
layer on the inner surface of conduit 120, with sufficient
thickness to allow a smaller diameter mandrel 320 to be used. In
some cases, trauma to conduit 120 (e.g. a vein) can be reduced.
[0187] In some cases, modifying element 627 may be configured to
deliver a kink resisting element, for example spine 510, such as a
robotic assembly constructed and arranged to laterally deliver
spine 510 about at least conduit 120 (e.g. about conduit 120 and an
inner layer of covering 110). In some cases, modifying element 627
can be configured to modify conduit 120, spine 510 and/or covering
110, such as to cause graft device 100 to be kink resistant or
otherwise enhance the performance of the graft device 100 produced
by system 10. In these graft device 100 modifying cases, modifying
element 627 can comprise a component selected from the group
consisting of: a robotic device such as a robotic device configured
to apply spine 510 to conduit 120; a nozzle, such as a nozzle
configured to deliver agent 602; an energy delivery element, such
as a laser delivery element such as a laser excimer diode or CO2
laser, or another element configured to trim one or more components
of graft device 100; a fluid jet, such as a water jet or air jet
configured to deliver fluid during the application of covering 110
to conduit 120; a cutting element, such as a cutting element
configured to trim spine 510 and/or covering 110; a mechanical
abrader; and any combination thereof or other components.
Modification of covering 110 or other graft device 100 component by
modifying element 627 can occur during the production of covering
110 and/or after covering 110 has been applied to conduit 120.
Modification of one or more spines 510 can be performed prior to
and/or after spine 510 has been applied to surround conduit 120. In
some cases, modifying element 627 can be used to cut or otherwise
trim covering 110 and/or a spine 510.
[0188] In an alternative embodiment, modification assembly 605 of
system 10 can be an additional component or assembly, separate from
MDD 300, such as a handheld device configured to remove solvent
and/or deliver spine 510. In some cases, modification assembly 605
may comprise a handheld laser, such as a laser device which can be
hand operated by an operator. In some cases, modification assembly
605 may comprise a fan, vacuum or other gas propelling device
configured to remove solvent or other undesired material from areas
surrounding conduit 120 and/or covering 110. Modification assembly
605 can be used to modify graft device 100 after its removal from
MDD 300, such as prior to and/or during a graft device 100
implantation procedure.
[0189] Laser or other modifications to covering 110 can cause
portions of covering 110 to undergo physical changes, such as
hardening, softening, melting, stiffening, creating a resilient
bias, expanding, and/or contracting, and/or can also cause covering
110 to undergo chemical changes, such as forming chemical bonds
with an adhesive layer between the outer surface of conduit 120 and
covering 110 and/or a chemical change that reduces the amount of
solvent in covering 110. In some cases, modifying element 627 may
be configured to modify conduit 120, such that conduit 120 may
comprise a kink resisting or other performance enhancing element.
Modifications to conduit 120 can include but are not limited to a
physical change to one or more portions of conduit 120 selected
from the group consisting of: drying; hardening; softening;
melting; stiffening; creating a resilient bias; expanding;
contracting; and any combination thereof or other changes.
Modifications of conduit 120 can cause conduit 120 to undergo
chemical changes, such as a chemical change that results in a
reduction in solvent in covering 110 and/or a chemical change that
forms chemical bonds with an adhesive layer between an outer
surface of conduit 120 and spine 510 and/or covering 110.
[0190] Covering 110 can include an inner layer and an outer layer.
The inner layer can include an adhesive component and/or exhibit
adhesive properties. The inner layer can be delivered separate from
the outer layer, for example, delivered from a separate nozzle or
at a separate time during the process of creating covering 110.
Selective adhesion between the inner and outer layers can be
configured to provide kink resistance. Spine 510 can be placed
between the inner and outer layers of covering 110, such as is
described herein.
[0191] In some cases, MDD 300 can be configured to deliver covering
110 and/or an adhesive layer according to set parameters configured
to produce a kink resistant element in and/or provide kink
resisting properties to graft device 100. For example, an adhesive
layer can be delivered to conduit 120 for a particular length of
time, followed by delivery of material 350 for another particular
length of time. An application parameters may include but may not
be limited to: amount of adhesive layer and/or material 350
delivered; rate of adhesive layer and/or material 350 delivered;
nozzle 310 distance to mandrel 320 and/or conduit 120; linear
travel distance of nozzle 310 or a fiber modifying element 627
along its respective drive assembly (for example, linear drive
assembly 345 or 645); linear travel speed of nozzle 310 or a fiber
modifying element 627 along its respective drive assembly;
compositions of material 350 and/or adhesive layer; concentrations
of material 350 and/or adhesive layer; solvent compositions and/or
concentrations; covering 110 inner and outer layer compositions
and/or concentrations; spontaneous or sequential delivery of
material 350 and the adhesive layer; flow rate of material 350
delivered to nozzle 310; pressure of material delivered to nozzle
310; temperature of nozzle 310; voltage applied to nozzle 310;
voltage applied to mandrel 320; temperature of mandrel 320;
viscosity of material 350; temperature within chamber 20; relative
humidity within chamber 20; airflow within chamber 20; and any
combination thereof or other parameters.
[0192] Nozzle 310 can be constructed of stainless steel, such as
passivated 304 stainless steel. A volume of space surrounding
nozzle 310 can be maintained free of objects or substances which
can interfere with the material 350 delivery process. Nozzle 310
geometry and orientation, as well as the temperature, pressure
and/or electrical potential voltages (e.g. as applied between
nozzle 310 and mandrel 320) can be chosen to control production of
covering 110.
[0193] Mandrel 320 can be positioned in a particular spaced
relationship from assembly 305 and/or assembly 605, and nozzle 310
and/or modifying element 627, respectively. In the illustrated
embodiment, mandrel 320 may be positioned above and below
assemblies 605 and 305, respectively. In some cases, mandrel 320
can be positioned above, below, to the right and/or to the left of,
assembly 305 and/or assembly 605. The distance between mandrel 320
and the tip of nozzle 310 and/or modifying element 627 can be less
than about 20 centimeter (cm), or less than about 15 cm, such as a
distance of from about 12.2 cm to about 12.8 cm or about 12.5 cm.
In some cases, multiple nozzles 310 and/or multiple modifying
elements 627, for example components of similar or dissimilar
configurations, can be positioned in various orientations relative
to mandrel 320. In some cases, the distance between nozzles 310
and/or modifying elements 627 and mandrel 320 may vary along the
length of their respective travel along mandrel 320, such as to
create a varying pattern of covering 110 along conduit 120. In some
cases, nozzle 310 and/or modifying element 627 distances from
mandrel 320 can vary continuously during the application of
material 350 and/or the distance can vary for one or more set
periods of time during the process.
[0194] In some cases, an electrical potential may be applied
between nozzle 310 and one or both of conduit 120 and mandrel 320
(e.g. when MDD 300 may comprise at least an electrospinning device,
such as to create at least a portion of covering 110 and/or a spine
510). The electrical potential can draw at least one fiber from
material delivery assembly 305 to conduit 120. Conduit 120 can act
as the substrate for an electrospinning process, collecting the
fibers that may be drawn from material delivery assembly 305 by the
electrical potential. In some cases, mandrel 320 and/or conduit 120
may have a lower voltage than nozzle 310 to create the desired
electrical potential. For example, the voltage of mandrel 320
and/or conduit 120 can be a negative or zero voltage while the
voltage of nozzle 310 can be a positive voltage. Mandrel 320 and/or
conduit 120 can have a voltage of about -5 kiloVolts (kV) (e.g.,
about: -10 kV, -9 kV, -8 kV, -7 kV, -6 kV, -5 kV, -4.5 kV, -4 kV,
-3.5 kV, -3.0 kV, -2.5 kV, -2 kV, -1.5 kV, or -1 kV) and the nozzle
310 can have a voltage of about +15 kV (e.g., about: 2.5 kV, 5 kV,
7.5 kV, 12 kV, 13.5 kV, 15 kV, 17 kV, or 20 kV). In some cases, the
potential difference between nozzle 310 and mandrel 320 and/or
conduit 120 can be from about 5 kV to about 30 kV. This potential
difference may draw fibers from nozzle 310 to conduit 120. In some
cases, nozzle 310 may be electrically charged with a potential of
between +15 kV and +17 kV while mandrel 320 may be at a potential
of about -2 kV. In some cases, mandrel 320 may be a fluid mandrel,
such as the fluid mandrel described in applicant's U.S. Pat. No.
9,656,417, issued May 23, 2017, the content of which is
incorporated herein by reference in its entirety for all
purposes.
[0195] Mandrel 320 can be configured to rotate about an axis, such
as central axis 335 of mandrel 320, with axis 328 of nozzle 310 may
be oriented orthogonal to axis 335. In some cases, axis 328 of
nozzle 310 may be horizontally offset from axis 335. The rotation
around axis 335 may allow covering 110 to be applied along all
sides, or around a portion of an entire circumference of conduit
120. In some cases, two motors 341a and 341b may be used to rotate
mandrel 320. In some cases, MDD 300 can include a single motor
configured to rotate mandrel 320. In some cases, mandrel 320 may
not be rotated (e.g. when mandrel 320 may be a flat plate). The
rate of rotation of mandrel 320 can determine how fibers may be
applied to one or more segments of conduit 120. For example, for a
thicker portion of covering 110, the rotation rate can be slower
than when a thinner portion of covering 110 is desired. In some
cases, mandrel 320 may be rotated at a rate (e.g. a minimum,
maximum or average rate) of from about 100 rotations per minute
(rpm) to about 500 rpm, such as a rate of from about 200 rpm to
about 300 rpm, from about 240 rpm to about 260 rpm, or about 250
rpm.
[0196] In addition to mandrel 320 rotating around axis 335, the
material delivery assembly 305 can move, such as when driven by
linear drive assembly 345 in a reciprocating or oscillating
horizontal motion (to the left and right of the page). Drive
assembly 345, as well as linear drive assembly 645 which operably
attaches to assembly 605, can individually or collectively comprise
a linear drive assembly, such as a belt-driven and/or gear-driven
drive assembly comprising two or more pulleys driven by one or more
stepper motors. In some cases, assemblies 305 and/or 605 can be
constructed and arranged to rotate around axis 335, rotating
element not shown. The length of linear drive assemblies 345 and/or
645 and the linear motion applied to assemblies 305 and 605,
respectively, can vary based on the length of conduit 120 to which
a covering 110 is produced and/or a covering 110 modification is
applied. For example, the supported linear motion of linear drive
assemblies 345 and/or 645 can comprise a translation distance of
from about 10 centimeter (cm) to about 50 cm, such as to cause a
translation of assembly 305 and/or 605 from about 27 cm to about 31
cm, or about 29 cm. Rotational speeds of mandrel 320 and
translational speeds of assemblies 305 and/or 605 can be relatively
constant, or can be varied during the material 350 delivery process
of assembly 305 and/or modification procedure of assembly 605. In
some cases, assemblies 305 and/or 605 may be translated (e.g. back
and forth) at a relatively constant translation rate from about 40
millimeters per second (mm/sec) to about 150 mm/sec, such as to
cause nozzle 310 and/or modifying element 627 to translate at a
rate of from about 50 millimeter per second (mm/sec) to about 80
mm/sec, from about 55 mm/sec to about 65 mm/sec, or about 60
mm/sec, during the majority of its travel. In some cases, system 10
may be constructed and arranged to rapidly change directions of
translation (e.g. by maximizing deceleration before a direction
change and/or maximizing acceleration after a direction
change).
[0197] Assemblies 305 and/or 605 can move along the entire length
and/or along specific portions of the length of conduit 120. In
some cases, delivery of material 350 and/or a modification may be
applied to a length coordinating to a portion or the entire length
of conduit 120 plus an additional about 5 cm (e.g. applied to
mandrel 320). In another embodiment, material 350 and/or a
modification may be applied to a length coordinating to a portion
or the entire length of conduit 120 plus at least about 1 cm.
Assemblies 305 and/or 605 can be controlled such that specific
portions along the length of conduit 120 may be reinforced with a
greater amount (e.g. thicker segment) of covering 110 as compared
to other or remaining portions. In some cases, assemblies 305
and/or 605 can be controlled such that specific portions of the
length of conduit 120 may include one or more kink resistant
elements (e.g. one or more spines 510) positioned at those one or
more specific conduit 120 portions. In addition, conduit 120 can be
rotating around axis 335 while assemblies 305 and/or 605 move, via
linear drive assemblies 345 and/or 645, respectively, to position
assemblies 305 and/or 605 at the particular portion of conduit 120
and/or mandrel 320 to which material 350 may be delivered and/or
covering 110 may be modified.
[0198] System 10 can also include a power supply, power supply 302
configured to provide power to material delivery assembly 305 (e.g.
to a pump or other fluid propulsion mechanism of material delivery
assembly 305). Power supply 302 can be configured to provide
electric potentials to nozzle 310 and mandrel 320, and/or to supply
power to other components of system 10 such as linear drive
assemblies 345 and 645 and assembly 605. Power supply 302 can be
connected, either directly or indirectly, to at least one of
mandrel 320 or conduit 120. Power can be transferred from power
supply 302 to one or more components (such as each component) by,
for example, one or more wires.
[0199] System 10 can include an environmental control assembly
including environmental chamber, chamber 20, that may surround MDD
300 (e.g. at least during the creation of covering 110). System 10
can be constructed and arranged to control the environmental
conditions within chamber 20, such as to control one or more areas
surrounding material delivery assembly 305 and/or mandrel 320
during the application of covering 110 to conduit 120. Chamber 20
can include inlet port assembly 21 and outlet port assembly 22.
Inlet port assembly 21 and/or outlet port assembly 22 can include
one or more components such as one or more components selected from
the group consisting of: a fan; a source of a gas such as a dry
compressed air source; a source of gas at a negative pressure; a
vapor source such as a source including a buffered vapor, an
alkaline vapor and/or an acidic vapor; a filter such as a high
efficiency particulate air (HEPA) filter; a dehumidifier; a
humidifier; a heater; a chiller; and electrostatic discharge
reducing ion generator; and any combination thereof. Chamber 20 can
include one or more environmental control components that can
monitor and/or control temperature, humidity and/or pressure within
chamber 20 (e.g. one or more environmental control components
controlled by environmental controller 35). Chamber 20 can be
constructed and arranged to provide relatively uniform ventilation
about mandrel 320 (e.g. about conduit 120, covering 110 and/or
spine 510) including an ultra-dry (e.g. .ltoreq.about 2 part per
million (ppm) water or other liquid content) compressed gas (e.g.
air) source may be configured to reduce humidity within chamber 20.
Inlet port assembly 21 and outlet port assembly 22 can be oriented
to purge air from the top of chamber 20 to the bottom of chamber 20
(e.g. to remove vapors of one or more solvents such as
hexafluoro-2-propanol (HFIP), which can tend to settle at the
bottom of chamber 20). Chamber 20 can be constructed and arranged
to replace the internal volume of chamber 20 at least once every
about 3 minutes, or once every about 1 minute, or once every about
30 seconds. Outlet port assembly 22 can include one or more filters
24 (e.g. replaceable cartridge filters) which may be suitable for
retaining solvent or other potentially harmful components of
material 350 (e.g. by filtering vapor including solvent) or to
retain other undesired materials evacuated from chamber 20. In some
cases, inlet port assembly 21 can include one or more filters 23
which are similarly suitable for retaining solvent or other
undesired materials delivered into chamber 20. Chamber 20 can be
constructed and arranged to maintain a flow rate through chamber 20
of at least about 30 liters per minute (L/min), such as at least
about 45 L/min or at least about 60 L/min, such as during an
initial purge procedure. Subsequent to an initial purge procedure,
a flow rate of at least about 5 L/min, at least about 10 L/min, at
least about 20 L/min or at least about 30 L/min can be maintained,
such as to maintain a constant humidity level (e.g. a relative
humidity from about 20% to about 24%). Chamber 20 can be
constructed and arranged to control temperature, such as to control
temperature within chamber 20 to a temperature from about
15.degree. C. to about 25.degree. C., such as from about 16.degree.
C. to about 20.degree. C. with a relative humidity from about 20%
to about 24%. In some cases, one or more objects or surfaces within
chamber 20 may be constructed of an electrically insulating
material and/or may not include sharp edges or exposed electrical
components. In some cases, one or more metal objects may be
positioned within chamber 20 and may be electrically grounded
and/or maintained at a particular desired voltage level (e.g. a
voltage level different than the voltage level of nozzle 310 and/or
different than the voltage level of mandrel 320).
[0200] In some cases, system 10 may be configured to produce a
first graft device, graft device 100' based on one or more
component or process parameters. In some cases, graft device 100'
may comprise conduit 120' and a covering 110' applied by MDD 300
(e.g. a 3D printer or other layered deposition device). Covering
110' can be produced by material delivery assembly 305 supplied
with material 350, such as at a flow rate of about 15 milliliter
per hour (ml/hr). Cumulative application time of covering 110' can
comprise an approximate time period of from about 11 minutes and 40
seconds to about 17 minutes and 30 seconds. The cumulative
application time of covering 110' can comprise a time period of
from about 11 minutes and 40 seconds when conduit 120' may comprise
an outer diameter of from about 3.4 millimeter (mm) to about 4.2
mm, a time period of about 14 minutes and 0 seconds when conduit
120' may comprise an outer diameter from about 4.2 mm to about 5.1
mm, and/or a time period of about 17 minutes and 30 seconds when
conduit 120' may comprise an outer diameter from about 5.1 mm to
about 6.0 mm.
[0201] Covering 110' can comprise an average fiber size of about
7.8 micrometer (.mu.m), such as a population of fiber diameters
with an average fiber size of about 7.8 .mu.m with a standard
deviation of about 0.45 .mu.m. Covering 110' can comprise an
average porosity of about 50.4%, such as a range of porosities with
an average of about 50.4% and a standard deviation of about 1.1%.
Covering 110' can comprise a strength property selected from the
group consisting of: stress measured at about 5% strain comprising
a level from about 0.4 megapascal (MPa) to about 1.1 MPa; ultimate
stress at a level of from about 4.5 MPa to about 7.0 MPa; ultimate
strain at a level of from about 200% to about 400%; and any
combination thereof. Covering 110' can comprise a compliance from
about 0.2.times.10.sup.-4/mmHg to about 3.0.times.10.sup.-4/mmHg
when measured in arterial pressure ranges. Covering 110' can
comprise an elastic modulus from about 10 MPa to about 15 MPa.
Covering 110' can be constructed and arranged with a targeted
suture retention strength, such as an approximate suture retention
strength of from about 2.0 Newton (N) to about 4.0 N with 6-0
Prolene.RTM. suture (or equivalent) and/or from about 1.5 N to
about 3.0 N with 7-0 Prolene.RTM. suture (or equivalent). In some
cases, graft device 100' may include a spine 510', such as a spine
510' placed between inner and outer layers of covering 110' (e.g.
placed after one-third of the total thickness of covering 110' may
be applied about conduit 120' or otherwise produced).
[0202] In some cases, system 10 may be configured to produce a
second graft device, graft device 100'' based on one or more
component or process parameters. In some cases, graft device 100''
may comprise conduit 120'' and a covering 110'' produced by MDD
300. Covering 110'' can be applied via material delivery assembly
305 supplied with material 350 at a flow rate of about 20
milliliter per hour (ml/hr). Cumulative application time of
covering 110'' can comprise an approximate time period of from
about 9 minutes and 30 seconds to about 13 minutes and 40 seconds.
The cumulative application time of covering 110'' can comprise a
time period of about 9 minutes and 30 seconds when conduit 120''
may comprise an outer diameter from about 3.4 millimeters (mm) to
about 4.2 mm; a time period of about 11 minutes and 30 seconds when
conduit 120'' may comprise an outer diameter from about 4.2 mm to
about 5.1 mm, and/or a time period of about 13 minutes and 40
seconds when conduit 120'' may comprise an outer diameter from
about 5.2 mm to about 6.0 mm.
[0203] Covering 110'' can comprise an average fiber size of about
8.6 micrometer (.mu.m), such as a population of fiber diameters
with an average fiber size of about 8.6 .mu.m with a standard
deviation of about 0.45 .mu.m. Covering 110'' can comprise an
average porosity of about 46.9%, such as a range of porosities with
an average of about 46.9% and a standard deviation of about 0.9%.
Covering 110'' can comprise a strength property selected from the
group consisting of: stress at about 5% strain comprising a level
from about 0.6 MPa to about 1.3 MPa; ultimate stress at a level of
from about 5.0 MPa to about 7.5 MPa; ultimate strain at a level of
from about 200% to about 400%; and any combination thereof.
Covering 110'' can comprise a compliance from about
0.2.times.10.sup.-4/mmHg to about 3.0.times.10.sup.-4/mmHg when
measured in arterial pressure ranges. Covering 110'' can comprise
an elastic modulus from about 12 MPa to about 18 MPa. Covering
110'' can be constructed and arranged with a targeted suture
retention strength, such as an approximate suture retention
strength of from about 2.3 Newton (N) to about 4.3 N with 6-0
Prolene.RTM. suture and/or from about 2.0 N to about 3.5 N with 7-0
Prolene.RTM. suture. In some cases, graft device 100'' may include
a spine 510'', such as a spine 510'' placed between inner and outer
layers of covering 110'' (e.g. placed after one-third of the total
thickness of covering 110'' may be applied about conduit 120'' or
otherwise produced).
[0204] Coverings 110' and 110'' can comprise one or more similar
features and/or one or more dissimilar features. Covering 110'' of
graft device 100'' can comprise more bonds between fibers than
covering 110' of graft device 100'. The increased number of bonds
can result in a higher covering 110'' density which can be
configured to limit cellular infiltration into graft device 100''
(e.g. to increase the graft durability in vivo). Covering 110'' can
comprise fibers that are flatter (i.e. more oval versus round)
and/or denser than fibers of covering 110'. Covering 110'' can have
a greater resiliency than covering 110'.
[0205] System 10 can comprise one or more solvent-reducing
materials, such as solvent-reducing material 640 shown positioned
within supply 620. In some cases, modification assembly 605 may be
configured to deliver solvent-reducing material 640 to conduit 120
and/or covering 110 (e.g. onto conduit 120 and/or covering 110). In
some cases, solvent-reducing material 640 may comprise a material
selected from the group consisting of: a desiccant; a material
configured to bond with solvent; a material configured to absorb
solvent; a neutralizing agent configured to neutralize solvent
(e.g. make less toxic or otherwise less harmful to the patient);
and any combination thereof. In some cases, solvent-reducing
material 640 may be delivered onto conduit 120 to create a barrier
(e.g. a barrier layer) between conduit 120 and an applied layer of
covering 110 comprising solvent. In some cases, solvent-reducing
material 640 may comprise a material selected from the group
consisting of: desiccant; lipid; phospholipid; buffer; pH buffer;
polyethylene; polytetrafluoroethylene (PTFE); fibrin; albumin;
gelatin; oil; wax; polyethylene glycol (PEG); carbon particle;
activated carbon particle; alkaline material; powder; carbon
particles; polymer beads; polymer gel; wicking fibrous membrane;
solvent capillary transport system; ionizing gas; plasma; and any
combination thereof. In some cases, solvent-reducing material 640
may comprise a pH buffer and/or alkaline material configured to
prevent undesired pH changes in conduit 120. In some cases,
solvent-reducing material 640 may comprise an ionizing gas
configured to absorb or otherwise neutralize solvent. For example,
a "cloud" of ionizing gas may be positioned proximate the conduit
120 such that material delivered by material delivery assembly 305
pass through the ionizing gas and attenuate the negative effects of
solvent.
[0206] In some cases, solvent-reducing material 640 may comprise a
material positioned as a barrier between conduit 120 and covering
110. In some cases, solvent-reducing material 640 may comprise a
removable or otherwise temporary barrier (e.g. a barrier removed
prior to implantation of graft device 100 in the patient). In some
cases, solvent-reducing material 640 may be applied to a surface of
the conduit 120 and/or covering 110 (e.g. an inner layer of the
covering 110). In some cases, solvent-reducing material 640 may be
delivered to conduit 120 and/or covering 110 during application of
material by material delivery assembly 305. In some cases,
solvent-reducing material 640 may comprise a material configured to
neutralize solvent, such as neutralizing agent 641 described
herein.
[0207] System 10 can comprise one or more solvent neutralizing
materials, such as solvent neutralizing material 641 shown
positioned within supply 620. Solvent neutralizing material 641 can
comprise a material configured to reduce injury to conduit 120 by
solvent (e.g. when conduit 120 comprises a vein segment or other
living tissue). In some cases, modification assembly 605 may be
configured to deliver solvent neutralizing material 641 to conduit
120 and/or covering 110 (e.g. onto conduit 120 and/or covering
110), such as an application that may occur prior to the delivery
of covering 110, during the delivery of covering 110 (e.g.
delivered while material 350 may be delivered, or delivered to a
partial layer of covering 110 when no material 350 may be applied)
and/or after the delivery of covering 110. In some cases, solvent
neutralizing material 641 may comprise a material selected from the
group consisting of: a buffer; polyethylene;
polytetrafluoroethylene (PTFE); fibrin; albumin; gelatin;
polyethylene glycol (PEG); carbon particle; activated carbon
particle; sulfate; phosphate; ADP; ATP converted from ADP; an acid
reducing material; a lipid; a phospholipid; an acidophilic
bacteria; an alkaliphilic bacteria; and any combination thereof. In
some cases, solvent neutralizing material 641 may be positioned
about at least a portion of conduit 120 and/or an inner layer of
covering 110 to function as a barrier to prevent interaction
between solvent and conduit 120. In some cases, the barrier can be
configured to be removable (e.g. dissolvable or otherwise
removable) prior to implantation of graft device 100 in the
patient. In some cases, solvent neutralizing material 641 (and the
resultant barrier) can comprise a material selected from the group
consisting of: lipid; phospholipid; buffer; pH buffer;
polyethylene; PTFE; fibrin; albumin; gelatin; oil; wax; PEG; carbon
particle; activated carbon particle; alkaline material; powder;
carbon particles; polymer beads; polymer gel; and any combination
thereof.
[0208] System 10 can comprise one or more solvent-reducing
elements, such as solvent-reducing element 40 and/or
solvent-reducing element 361 of FIG. 3. Solvent-reducing element
40, shown positioned in chamber 20, and solvent-reducing element
361, shown positioned in NIDD 300, can comprise one or more devices
or components configured to extract solvent, such as to extract
solvent from conduit 120 (e.g. from the wall of conduit 120), from
covering 110 (e.g. from one or more layers of covering 110), and/or
from locations surrounding these (e.g. one or more locations within
chamber 20). Solvent-reducing element 40 and/or 361 can comprise a
component selected from the group consisting of: fan; nozzle;
filter; electrostatic filter; osmotic membrane; fluid delivery
element; fluid extraction element; vacuum applying element;
agitating element; heating element; cooling element; sponge;
diffusion enhancing element; desiccant; forced convection element;
and any combination thereof. In some cases, solvent-reducing
element 40 and/or 361 can comprise a solvent-reducing material
(e.g. a material configured to reduce solvent or other undesired
substance), such as a material selected from the group consisting
of: a desiccant; a material configured to bond with solvent; a
material configured to absorb solvent; a material configured to
neutralize solvent (e.g. make less toxic or otherwise less harmful
to the patient); and any combination thereof.
[0209] In some cases, solvent-reducing element 40 and/or 361 may
comprise a fluid extraction element configured to reduce solvent,
such as a vacuum applying element. In some cases, nozzle 310 and/or
modifying element 627 can comprise the solvent-reducing element
configured to extract fluid and/or apply a vacuum. In some cases,
solvent-reducing element 40 and/or 361 may comprise a temperature
control element configured to reduce solvent, such as when
environmental controller 35 may adjust or may otherwise control the
temperature within chamber 20 to cause a reduction in solvent. In
some cases, solvent-reducing element 40 and/or 361 may comprise a
fluid delivery element configured to deliver a gas or other fluid
proximate conduit 120 to remove solvent (e.g. when nozzle 310
and/or modifying element 627 comprise the solvent-reducing element
delivering the fluid to enhance diffusion of solvent). In some
cases, solvent-reducing element 40 and/or 361 comprise an agitating
element, such as a fan or other agitating element proximate conduit
120 (e.g. to create a stream of laminar or turbulent gas flow
proximate conduit 120). In some cases, solvent-reducing element 40
and/or 361 may comprise a humidity control element configured to
remove solvent. In some cases, solvent-reducing element 40 and/or
361 may comprise at least a replaceable portion (e.g. a disposable
portion used on a single patient only). In some cases,
solvent-reducing element 40 and/or 361 may comprise a translatable
element, such as when nozzle 310 and/or modifying element 627 may
comprise the solvent-reducing element and may be translated by
linear drive assemblies 345 and/or 645, respectively. In some
cases, solvent-reducing element 40 and/or 361 may comprise one or
more elements configured to rotate and/or translate relative to
conduit 120.
[0210] System 10 can comprise one or more sensors, such as one or
more sensors configured to detect the presence or level of one or
more solvents (e.g. sensors that produce a signal related to a
solvent level). In some cases, chamber 20 may comprise sensor 26
comprising one or more sensors. In some cases, controller 30 may
comprise sensor 36 comprising one or more sensors. In some cases,
mandrel 320 may comprise sensor 329 comprising one or more sensors
(e.g. a sensor configured to measure a parameter of conduit 120
such as a level of solvent). In some cases, material delivery
assembly 305 may comprise sensor 309 comprising one or more
sensors. In some cases, MDD 300 may comprise sensor 369 comprising
one or more sensors. In some cases, modification assembly 605 may
comprise sensor 606 comprising one or more sensors. Sensor 26, 36,
329, 309, 369 and/or 606 can individually or any combination
thereof comprise one or more sensors configured to measure a
parameter (e.g. configured to produce a signal related to the level
of a solvent) and may produce a signal based on the measured
parameter. In some cases, sensor 26, 36, 329, 309, 369 and/or 606
can be configured to measure the concentration or other amount of
solvent present within conduit 120 (e.g. within a wall of conduit
120), covering 110 and/or a location within chamber 20. System 10
can be configured to adjust one or more system parameters based on
the sensor signal produced by sensor 26, 36, 329, 309, 369 and/or
606. In some cases, system 10 can be configured to alert an
operator that the level of solvent present in graft device 100 may
be below a threshold (e.g. to indicate that graft device 100 may be
ready for implantation based on a measured level of solvent
detected).
[0211] In some cases, sensor 26, 36, 329, 309, 369 and/or 606
comprise one or more sensors selected from the group consisting of:
optical sensor; temperature sensor; humidity sensor; pH sensor;
ganged litmus paper instrument; strain gauge; accelerometer; load
cell; electrochemical sensor; pressure sensor; chemical sensor; a
color changing chemical sensor; a photoionization sensor; fluorine
sensor; a temperature sensor configured to measure cooling of the
conduit 120 (e.g. to assess evacuation of solvent); one or more
temperature sensors configured to measure the temperature
difference between inlet port assembly 21 and outlet port assembly
22; a sensor configured to measure the weight of at least a portion
of graft device 100; a sensor configured to measure the mass of at
least a portion of graft device 100; a sensor configured to measure
the acidity of at least a portion of graft device 100; a sensor
configured to measure a parameter of the exhaust of chamber 20
(e.g. exhaust through outlet port assembly 22); and any combination
thereof. System 10 can be configured to adjust one or more system
parameters based on the one or more signals produced by one or more
sensors 26, 36, 329, 309, 369 and/or 606. The one or more system
parameters adjusted can comprise one or more parameters selected
from the group consisting of: temperature proximate the conduit
120; flow rate of fluid proximate the conduit 120; rotation rate of
the conduit 120; translation rate of the conduit 120; rotation rate
of material delivery assembly 305; translation rate of the material
delivery assembly 305; a nozzle 310 to a mandrel 320 distance; and
any combination thereof. The one or more system parameters can be
adjusted prior to, during and/or after delivery of covering 110 to
conduit 120.
[0212] In some cases, sensor 26, 36, 329, 309, 369 and/or 606 may
comprise one or more sensors configured to produce a signal
representing a solvent parameter level (e.g. a solvent
concentration or other quantitative assessment of the presence of
solvent). System 10 can be configured to reduce solvent until the
solvent parameter level reaches a threshold (e.g. falls below a
maximum level). For example, system 10 can be configured to perform
a function selected from the group consisting of: maintaining graft
device 100 within chamber 20 (e.g. maintaining graft device 100
within chamber 20 in a sterile condition and/or under controlled
environmental conditions); rotating the graft device 100 (e.g.
rotating conduit 120 and at least a portion of covering 110);
providing a flow of gas proximate the graft device 100; providing
an elevated temperature proximate the graft device 100; providing a
desiccant proximate the graft device 100; and any combination
thereof.
[0213] In some cases, material delivery assembly 305 may be
configured to deliver fibers with an aspect ratio above 1 and/or to
deliver hollow fibers, such that solvent more rapidly evacuates the
fiber. In some cases, material delivery assembly 305 may be
configured to deliver fibers with an aspect ratio from about 1.01:1
to about 10:1.
[0214] In some cases, system 10 may comprise one or more functional
elements, such as functional element 25 shown positioned on chamber
20. Functional element 25 can comprise an element configured to
remove solvent and/or to reduce the effects of solvent on conduit
120 (e.g. a vein segment or other living tissue). In some cases,
functional element 25 may comprise an element selected from the
group consisting of: fan; nozzle; filter; electrostatic filter;
osmotic membrane; fluid delivery element; fluid extraction element;
vacuum applying element; agitating element; heating element;
cooling element; sponge; diffusion enhancing element; desiccant;
forced convection element; and any combination thereof. In some
cases, functional element 25 may comprise one or more elements
positioned in MDD 300 or another component of system 10.
[0215] In some cases, system 10 may be configured to reduce solvent
by rotating the conduit 120. For example, system 10 can be
configured to perform a rotation with or without the simultaneous
delivery of fibers to conduit 120, such as by rotating at an
increased rotational velocity during delivery of fibers, and/or a
rotation that may occur while no fibers may be delivered by
material delivery assembly 305 (e.g. a rotation after delivery of
covering 110 may be complete). In some cases, system 10 may be
configured to rotate conduit 120 and/or covering 110 at a minimum
velocity (e.g. a constant or variable rate that may include a rate
greater than about 250 rotations per minute (rpm)) for a minimum
time period (e.g. longer than about 1 second), in order to
sufficiently reduce the amount of solvent present in graft device
100. In some cases, system 10 may be configured to rotate covering
110 at a first rate while covering 110 may be being delivered by
material delivery assembly 305, and to rotate covering 110 at a
second rate (e.g. a higher rate) after the delivery of covering 110
may be completed.
[0216] While conduit 120 may be described in relation to a hollow,
tubular structure, any geometry may be considered within the scope
of the present disclosure, including both non-hollow and/or
non-tubular structures. Similarly, while device 100 may be
described in terms of a graft device or other device configured to
fluidly connect two or more anatomical locations (e.g. two or more
blood vessels), graft device 100 can comprise any type of implant
for a patient. In some cases, graft device 100 may be configured as
an implant used to replace, augment or otherwise treat cartilage,
ligament, bone, a disc, soft tissue and/or other tissue of the
patient.
[0217] The foregoing description and accompanying drawings set
forth a number of examples of representative embodiments at the
present time. Various modifications, additions and alternative
designs may become apparent to those skilled in the art in light of
the foregoing teachings without departing from the spirit hereof,
or exceeding the scope hereof, which is indicated by the following
claims rather than by the foregoing description. All changes and
variations that fall within the meaning and range of equivalency of
the claims are to be embraced within their scope.
* * * * *