U.S. patent application number 11/926609 was filed with the patent office on 2008-02-28 for scaffold and method for implanting cells.
Invention is credited to Peter M. Bonutti.
Application Number | 20080051624 11/926609 |
Document ID | / |
Family ID | 32095877 |
Filed Date | 2008-02-28 |
United States Patent
Application |
20080051624 |
Kind Code |
A1 |
Bonutti; Peter M. |
February 28, 2008 |
SCAFFOLD AND METHOD FOR IMPLANTING CELLS
Abstract
An improved method of implanting cells in the body of a patient
includes positioning viable cells on a support structure. One or
more blood vessels may be connected with the support structure to
provide a flow of blood through the support structure. A support
structure may be positioned at any desired location in a patient's
body. The support structure may be configured to replace an entire
organ or a portion of an organ. An organ or portion of an organ may
be removed from a body cells and/or other tissue is removed to
leave a collagen matrix support structure having a configuration
corresponding to the configuration of the organ or portion of an
organ. Alternatively, a synthetic support structure may be formed.
The synthetic support structure may have a configuration
corresponding to a configuration of an entire organ or only a
portion of an organ.
Inventors: |
Bonutti; Peter M.;
(Effingham, IL) |
Correspondence
Address: |
PAUL D. BIANCO: FLEIT, KAIN, GIBBONS,;GUTMAN, BONGINI, & BIANCO P.L.
21355 EAST DIXIE HIGHWAY
SUITE 115
MIAMI
FL
33180
US
|
Family ID: |
32095877 |
Appl. No.: |
11/926609 |
Filed: |
October 29, 2007 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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10457100 |
Jun 6, 2003 |
7299805 |
|
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11926609 |
Oct 29, 2007 |
|
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60387013 |
Jun 7, 2002 |
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Current U.S.
Class: |
600/36 ;
623/1.25; 623/2.1; 623/23.63; 623/23.64; 623/23.65; 623/23.75 |
Current CPC
Class: |
A61L 24/0015 20130101;
C12N 2533/54 20130101; C12N 5/0654 20130101; A61F 2002/2817
20130101; C12N 2533/90 20130101; A61F 2/4601 20130101; C12N 2501/10
20130101; C12N 2513/00 20130101; A61L 24/08 20130101; A61F
2210/0004 20130101; C12N 5/0062 20130101; A61F 2/0077 20130101;
C12N 5/0691 20130101; C12N 2501/11 20130101; C12N 2501/155
20130101; A61F 2/28 20130101; A61F 2002/2835 20130101; C12N 5/0068
20130101; A61F 2/02 20130101; C12N 2501/135 20130101; C12N 2501/105
20130101; Y10S 623/92 20130101 |
Class at
Publication: |
600/036 ;
623/001.25; 623/002.1; 623/023.63; 623/023.64; 623/023.65;
623/023.75 |
International
Class: |
A61F 2/02 20060101
A61F002/02 |
Claims
1. A method of performing an anastomotomy, which comprises:
providing a tubular implant having a support structure with a
plurality of pores formed therein for receiving cells; depositing
viable cells in said pores of said cylindrical support; providing a
blood vessel segment opening at an annular connector; providing a
body part opening at an annular connector; positioning said tubular
implant between said blood vessel segment and said body part with
each of said connectors of said tubular implant aligned with a
respective one of said annular connectors; attaching said annular
connector of said first blood vessel to a first of said annual
connectors of said tubular implant; and attaching said annular
connector of said body part to a second of said annual connectors
of said tubular implant.
2. The method according to claim 1, which further comprises
enclosing said support structure in an outer layer, said outer
layer at least partially blocking a radially outward flow of
blood.
3. The method according to claim 1, wherein the attaching step
includes stitching at least one of said annular connectors to said
tubular implant.
4. The method according to claim 1, wherein the attaching step
includes adhering at least one of said annular connectors to said
tubular implant.
5. The method according to claim 1, wherein said viable cells
include cells selected from the group consisting of endothelial
cells, mesenchymal cells, and smooth muscle cells.
6. The method according to claim 1, which further comprises
providing tissue growth induction materials on said support
structure.
7. The method according to claim 1, which further comprises
exposing said viable cells to a flow of blood through said tubular
implant after said tubular implant has been attached to said blood
vessel segments.
8. The method according to claim 1, which further comprises
providing a check valve in said tubular implant for directing blood
flow in only one direction through said tubular implant.
9. The method according to claim 8, wherein said forming said check
valve includes: providing a valve support structure in said tubular
implant, said valve support structure having pores formed therein;
and depositing smooth muscle cells in said pores of said valve
support structure.
10. The method according to claim 1, wherein said body part is a
further blood vessel segment.
11. The method according to claim 1, wherein said body part is an
organ.
12. The method according to claim 11, wherein said body part is a
heart.
13. The method according to claim 1, wherein said aligning step
includes: placing an expandable member against said tubular implant
while said expandable member is in an unexpanded state; and
expanding said expandable member to align said tubular implant with
at least one of said annular connectors.
14. The method according to claim 13, wherein: said placing step
includes inserting said expandable member within said tubular
implant in an unexpanded state; and said expanding step includes
expanding said expandable member to extend into at least one of
said annular connectors.
15. The method according to claim 13, which further comprises
contracting said expandable member after said attaching step.
16. The method according to claim 13, which further comprises:
inserting said expandable member remotely from said tubular
implant; and moving said expandable member to said tubular implant
via said blood vessel segment.
17. The method according to claim 16, which further comprises:
contracting said expandable member after said attaching step; and
subsequently removing said expandable member from said tubular
implant via said blood vessel segment.
18. The method according to claim 13, wherein said expandable
member expands by fluid pressure.
19. The method according to claim 13, wherein said expandable
member expands mechanically.
20. The method according to claim 13, wherein said expandable
member is a balloon.
21. The method according to claim 14, wherein said expandable
member spans said tubular implant and extends into both of said
annular connectors.
22. The method according to claim 14, which further comprises:
inserting a further expandable member within said tubular implant
in an unexpanded state; and expanding said further expandable
member to extend into the other of said annular connectors.
23. A method of performing an anastomotomy, which comprises:
providing tubular implant having two annular connectors; providing
a blood vessel segment opening at an annular connector; providing a
body part opening at an annular connector; positioning said tubular
implant between said blood vessel segment and said body part with
each of said annular connectors of said tubular implant aligned
with a respective one of annular connectors; inserting an
expandable member within said tubular implant in an unexpanded
state; expanding said expandable member to extend into at least one
of said annular connectors; attaching said annular connector of
said first blood vessel to a first of said annual connectors of
said tubular implant; attaching said annular connector of said body
part to a second of said annual connectors of said tubular
implant.
24. A tubular implant for connecting to at least one blood vessel
segment, comprising: a support structure having a plurality of
pores for receiving cells said having two annular connectors, each
of said connectors being configured to connect to at least one of
an annular connector of a blood vessel segment and an annular
connector of an organ; and viable cells deposited in said openings
of said cylindrical support.
25. The tubular implant according to claim 24, further comprising
an outer layer enclosing said support structure, said outer layer
at least partially blocking a radially outward flow of blood.
26. The tubular implant according to claim 24, wherein said support
structure is cylindrical.
27. The tubular implant according to claim 24, wherein said viable
cells include cells selected from the group consisting of
endothelial cells, mesenchymal cells, and smooth muscle cells.
28. The tubular implant according to claim 24, further comprising
tissue growth induction materials disposed on said support
structure.
29. The tubular implant according to claim 24, further comprising a
check valve disposed within said support structure and directing
blood flow in only one direction through said tubular implant.
30. The tubular implant according to claim 29, wherein said check
valve includes: a valve support structure connected to said tubular
implant and having pores formed therein; and smooth muscle cells
deposited on said valve support structure.
31. A method of replacing at least a portion of an organ, which
comprises: forming a mold of an organ to be replaced; removing said
organ from said mold; forming a support structure within said mold,
said support structure having pores formed therein; disposing
viable cells in said pores of said support structure to form a
replacement organ, said viable cells performing a function of said
organ to be replaced; and placing said replacement organ into a
patient to replace said organ.
32. A replacement organ for reproducing a function of an organ to
be replaced, comprising: a support structure shaped like an organ
to be replaced, said support structure having pores formed therein;
and viable cells disposed in said pores of said support structure
to form a replacement organ, said viable cells performing a
function of the organ to be replaced.
33. A matrix corresponding to at least a portion of an organ, the
portion having a function, the matrix comprising a support
structure having pores formed therein for receiving viable cells
and being shaped like the at least a portion of the organ.
34. The matrix according to claim 33, wherein said support
structure is a collagen matrix.
35. The matrix according to claim 33, wherein said collagen matrix
is an autograft taken from the at least a portion of an organ to be
replaced.
36. The matrix according to claim 33, wherein said collagen matrix
is an allograft taken from an at least a portion of an organ to be
replaced of a donor.
37. The matrix according to claim 33, further comprising a growth
factor disposed on said support structure.
38. The matrix according to claim 33, further comprising
pluripotent cells disposed on said support structure.
39. The matrix according to claim 38, further comprising growth
factors disposed on said matrix, said growth factors causing said
pluripotent cells to differentiate.
40. The matrix according to claim 38, further comprising a means
for attaching said pluripotent cells to said support structure.
41. A replacement for at least a portion of an organ having a
function, the replacement comprising: a support structure having
pores formed therein; viable cells of a first tissue type disposed
in said pores; and viable cells of a second tissue type disposed in
said pores.
42. A method for making a support structure of at least a part of
an organ to be replaced, which comprises: removing at least a part
of an organ having a support structure and cells connected to said
support structure from a donor; and removing said cells from said
support structure.
43. The method according to claim 42, wherein said removing step
includes treating said cells in a cytotoxic solution.
44. The method according to claim 42, wherein said removing step
includes irradiating said cells.
45. The method according to claim 42, wherein said removing step
includes exposing said cells to an environmental condition.
46. The method according to claim 42, wherein said support
structure is made of collagen.
47. An artificial support structure, comprising a polymeric matrix
with a configuration corresponding to a configuration of an organ
to be replaced.
48. The artificial support structure according to claim 47, wherein
said polymeric matrix has at least a biodegradable portion.
49. The artificial support according to claim 47, wherein said
polymeric matrix is a material selected from the group consisting
of cellulose, petroylglutamic acid, carboxymethylcellulose, and
polylactide.
50. The artificial support according to claim 47, further
comprising an additive selected from the group consisting of a
plasticizer, a citrate ester, a hexamethosebacate, an antibiotic,
and a growth factor.
51. The artificial structure according to claim 47, wherein said
polymeric matrix includes: a first biodegradable portion, said
first biodegradable portion degrading at a slower rate; and a
second biodegradable portion, said second biodegradable portion
degrading at a faster rate.
52. A replacement organ performing a function, comprising: a
support structure having pores formed therein; a first type of
cells disposed in said pores of said support structure, said first
type of cells being selected from the group consisting of renal
cells, stromal cells, fibroblasts, osteoblasts, mesodermal cells.
osteocondral cells, myoblasts, endothelial cells, mesenchymal
cells, and smooth muscle cells; and a second type of cells disposed
in said pores of said support structure, said second type of cells
being selected from the group consisting of renal cells, stromal
cells, fibroblasts, osteoblasts, mesodermal cells. osteocondral
cells, myoblasts, endothelial cells, mesenchymal cells, and smooth
muscle cells; said second type of cells being different.
53. A cardiac implant for insertion within a heart, comprising: a
support structure having pores formed therein; and endothelium
cells disposed in said pores of said support structure.
54. An implant for at least partially replacing an organ,
comprising: a support structure having pores formed therein; viable
cells disposed in said pores of said support structure; an outer
layer surrounding said support structure and at least inhibiting
blood flow from within; an afferent blood vessel connected to said
outer layer and configured to supply blood to said viable cells;
and an efferent blood vessel connected to said outer layer and
configured to receive blood from said viable cells.
55. The implant according to claim 54, which further comprises a
means for distributing the blood to all of said viable cells.
56. An implant assembly, comprising: a first implant according to
claim 54; and a second implant according to claim 54 connected to
said first implant.
57. The implant assembly according to claim 56, wherein said
implants are connected in series.
58. The implant assembly according to claim 57, further comprising
a manifold interconnecting said afferent blood vessel of said first
implant and said afferent blood vessel of said second implant, said
first implant and said second implant being connected in
parallel.
59. A method for minimally-invasive introduction of a scaffold for
at least partially replacing an organ, which comprises: providing a
ductile support structure having pores for receiving formed
therein; drawing said support structure into a wire-like shape;
inserting a cannula to a location for receiving said support
structure; and feeding said support structure to the location while
in said wire-like shape.
60. The method according to claim 59, which further comprises using
a collagen matrix as said ductile support structure.
61. The method according to claim 60, which further comprises
removing cells from an organ to produce said collagen matrix.
62. The method according to claim 59, which further comprises
locating said ductile support structure during said feeding step by
using a means for non-invasive imaging.
63. The method according to claim 59, which further comprises
imaging the location for receiving said receiving said support
structure during the feeding step.
64. A method for minimally-invasive introduction of a replacement
for at least part of an organ, which comprises: providing a ductile
support structure having pores for receiving formed therein;
drawing said support structure into a wire-like shape; inserting a
cannula to a location for receiving said support structure; feeding
said support structure to the location while in said wire-like
shape; reshaping said support structure at the location; and
depositing via cells on said support structure located at the
location by feeding said viable cells via said cannula to said
support structure.
65. The method according to claim 64, further comprising: providing
a ductile outer layer; forming said ductile outer layer into a
wire-like shape; feeding said ductile outer layer to the location
via said cannula; and enclosing said ductile support structure
within said ductile outer layer at the location before the
depositing step.
66. An implant for insertion in a kidney, comprising: a support
structure having pores formed therein; kidney cells disposed in
said pores of said support; an outer layer enclosing said support
structure said outer layer at least partially blocking a radially
outward flow of blood; an afferent blood vessel segment connected
to said outer layer and being configured to supply blood to said
kidney cells and being configured to connect to a renal artery; an
efferent blood vessel segment connected to said outer layer and
being configured to remove blood from said kidney cells and being
configured to connect to a renal vein; and a conduit connected to
said outer layer configured to connect to a ureter.
67. The implant according to claim 66, further comprising stromal
cells disposed on said support structure.
68. The implant according to claim 66, further comprising
fibroblasts disposed on said support structure.
69. The implant according to claim 66, further comprising
endothelial cells disposed on said support structure.
70. An implant for inserting in a bone, comprising: a support
structure having pores formed therein; bone cells disposed in said
pores of said support, said bone cells being selected from the
group consisting of osteoblasts and mesodermal cells; an outer
layer enclosing said support structure, said outer layer at least
partially blocking a radially outward flow of blood; an afferent
blood vessel segment connected to said outer layer and being
configured to supply blood to said bone cells and being configured
to connect to a renal artery; and an efferent blood vessel segment
connected to said outer layer and being configured to remove blood
from said bone cells and being configured to connect to a renal
vein.
71. The implant according to claim 70, wherein said outer layer is
configured to fill a portion of bone to be replaced.
72. The implant according to claim 70, further comprising
osteochondral cells disposed in said pores of said support
structure.
73. The implant according to claim 70, further comprising myoblasts
for promoting growth of muscle tissue.
74. An implant for inserting in a pancreas, comprising a support
structure having pores formed therein; viable cells disposed in
said pores of said support, said viable cells being selected from
the group consisting of endocrine cells, exocrine cells, and islets
of Langerhans; and an outer layer enclosing said support structure,
said outer layer at least partially blocking a radially outward
flow of blood.
75. An implant for at least partially replacing an organ performing
a function, comprising: a support structure having pores formed
therein; viable cells disposed in said pores of said support, said
viable cells performing the function of the organ; an outer layer
enclosing said support structure, said outer lawyer at least
partially blocking a radially outward flow of blood; and a means
for distributing blood flow within said outer layer to sustain said
viable cells.
76. An implant for at least partially replacing an organ performing
a function, comprising: a support structure having pores formed
therein; a first type of viable cells disposed in said pores of
said support; a second type of viable cells disposed in said pores
of said support; and a third type of viable cells disposed in said
pores of said support; said first type, said second type, and said
third type of cells performing the function of the organ.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application is a continuation of U.S. patent
application Ser. No. 10/457,100, filed Jun. 6, 2003. The '100
Application claimed the benefit under 35 U.S.C. .sctn.119(e) of
Provisional Application No. 60/387,013 filed Jun. 7, 2002.
BACKGROUND OF THE INVENTION
[0002] The present invention relates to the implanting of cells
into a body of a patient, and in particular to the implantation of
viable cells on a scaffold or support structure.
[0003] Various organs or other tissue in a patient's body may
become defective due to trauma, disease, or other causes.
Transplanting of organs and/or tissue has been utilized for the
treatment of defective organs. However, problems have been
encountered in securing an adequate number of suitable donor
organs. It is believed that it may be desirable to have a patient
grow a replacement organ, portion of an organ, or other body tissue
for replacement of any defective tissue, organ, or portion
thereof.
SUMMARY OF THE INVENTION
[0004] The present invention relates to a method of implanting
viable cells into a body of a patient. The viable cells may be
positioned on a support structure. One or more blood vessels in a
patient's body may be connected with the support structure at one
or more locations. The viable cells on the support structure may be
exposed to blood flow in the support structure. One or more support
structures may be provided and positioned in the patient's
body.
[0005] The support structure may be formed in many different ways.
One way in which the support structure may be formed is by removing
an organ or a portion of an organ from a body, either the patient's
own body or another body. Cells and/or other tissue may be removed
from the organ or portion of an organ to leave a collagen matrix
support structure having a configuration corresponding to the
configuration of the organ or portion of an organ. Viable cells are
positioned on the collagen matrix support structure. The support
structure, which has a configuration corresponding to the
configuration of an organ or portion of an organ, is positioned in
the patient's body with the viable cells disposed on the support
structure. Blood vessels may be connected with the support
structure as it is positioned in the patient's body.
[0006] The support structure may be formed by using an organ or
portion of an organ from a body that is either the patient's body
or another body as a pattern. Alternatively, the pattern may be
synthetically constructed to have a configuration corresponding to
the general configuration of an organ or portion of an organ in a
patient's body. The pattern may be at least partially enclosed with
mold material. The pattern and mold material are subsequently
separated to leave a mold cavity. The synthetic support structure
is subsequently shaped in the mold cavity. The synthetic support
structure may be formed as a unitary member or formed by one or
more intertwined strands.
[0007] One or more expandable members may be utilized to align an
implant and tissue in a patient's body. For example, one or more
balloons may be utilized to align a portion of a blood vessel with
a segment which is to be implanted into the blood vessel.
[0008] It should be understood that the present invention has a
plurality of different features which may be utilized separately or
in various combinations. It is also contemplated that the various
features of the invention may be utilized with known features from
the prior art. Although specific combinations of features have been
described herein, it is contemplated that other combinations of
features will be apparent to those skilled in the art and will be
formed.
BRIEF DESCRIPTION OF THE DRAWINGS
[0009] The foregoing and other features of the invention will
become more apparent upon a consideration of the following
description taken in connection with the accompanying drawings
wherein:
[0010] FIG. 1 is a schematic illustration depicting the manner in
which a support structure is connected with portions of one or more
blood vessels in a patient's body;
[0011] FIG. 2 is a fragmentary schematic plan view, taken generally
along the line 2-2 of FIG. 1, illustrating in the manner in which
viable cells may be positioned on the support structure of FIG. 1
and exposed to a flow of blood through the support structure;
[0012] FIG. 3 is a schematic illustration, generally similar to
FIG. 2, illustrating in the manner in which a barrier may be used
to direct the flow of blood through a support structure;
[0013] FIG. 4 is a fragmentary schematic sectional view, generally
similar to FIG. 3, depicting the manner in which a plurality of
blood vessels are connected with a support structure containing a
barrier to direct a flow of blood through the support structure and
to disperse the flow of blood in the support structure;
[0014] FIG. 5 is a schematic illustration of an organ, that is, a
kidney, in a patient's body;
[0015] FIG. 6 is a schematic illustration depicting the manner in
which a plurality of the support structures of FIGS. 1-4 may be
positioned in the organ of FIG. 5;
[0016] FIG. 7 is a schematic illustration depicting the manner in
which an organ or model of an organ may be used as a pattern to
form a mold cavity in which a synthetic support structure may be
formed;
[0017] FIG. 8 is a schematic illustration depicting the manner in
which a support structure on which viable cells are disposed is
utilized to replace a portion of a blood vessel;
[0018] FIG. 9 is a schematic illustration depicting the manner in
which a balloon is utilized to align the support structure and
portions of a blood vessel;
[0019] FIG. 10 is a schematic illustration, generally similar to
FIG. 9, illustrating the manner in which a plurality of balloons
may be utilized to align the support structure and portions of a
blood vessel;
[0020] FIG. 11 is a top view of an embodiment of a support
structure in the form of a three dimensional mesh of fibers.
DESCRIPTION OF SPECIFIC PREFERRED EMBODIMENTS OF THE INVENTION
General Description
[0021] An implant 20 is illustrated schematically in FIGS. 1 and 2.
The implant 20 includes a support structure or matrix 22 (FIG. 2)
which may have any desired configuration. A plurality of viable
cells 24 (FIG. 2) are positioned on the support structure 22.
Although the support structure 22 has been illustrated
schematically in FIGS. 1 and 2 as having a rectangular
configuration and the viable cells 24 have been illustrated
schematically as being disposed in a rectangular array on a
rectangular matrix, it is contemplated that the support structure
22 could have any desired configuration and that the viable cells
24 could be disposed in any desired arrangement on the support
structure.
[0022] In accordance with one of the features of the present
invention, one or more blood vessels 28 are connected with the
support structure 22 to provide for a flow of blood through the
support structure. Although the support structure 22 may be
connected with blood vessels 28 in many different ways, in the
specific arrangement illustrated in FIGS. 1 and 2, an arteriole (a
small artery) 32 and a venule (small vein) 34 are connected with
the support structure 22. This results in a flow of blood from left
to right, as indicated by arrows in FIGS. 1 and 2, through the
implant 20. The viable cells 24 are exposed to the flow of
blood.
[0023] Although the implant 20 has been illustrated in FIGS. 1 and
2 as being connected with an artery 32 and vein 34, it is
contemplated that the implant 20 could be connected with one or
more arteries or one or more veins. Thus, a portion of the same
artery or vein may be connected with opposite sides of the implant
20. Alternatively, a portion of one artery or vein may be connected
with one side of the implant 20 and a portion of another artery or
vein may be connected with the opposite side of the implant.
[0024] If desired, a plurality of portions of arteries and/or veins
may be connected with one side of the implant 20. Similarly, a
plurality of portions of arteries and/or veins may be connected
with the opposite side of the implant 20. The number of portions of
arteries and/or veins connected with the implant 20 will vary
depending upon the location where implant 20 is to be positioned in
a patient's body. The patient is a living human.
[0025] The interior of the support structure 20 has a plurality of
passages through which blood may flow. It is contemplated that
capillaries, arterioles, and/or venules may grow in the support
structure 20. The outer sides of the support structure 20 may be
formed of a material which is impervious to blood or a material
which restricts the flow of blood from the implant 20 to
surrounding tissue.
[0026] The implant 20 may be positioned at any desired location in
a patient's body. For example, the support structure 22 may be
positioned in an organ, that is, a functional unit of cells. The
organ in which the support structure 22 is positioned may be a
heart, blood vessel, brain, intestine, stomach, adrenal gland,
liver, pancreas, skeleton, spinal cord, or other organ. The support
structure 22 may be positioned in either soft tissue or hard
tissue.
[0027] The support structure 22 may have a configuration
corresponding to the configuration of an entire organ or a portion
of an organ. If the support structure 22 has a configuration
corresponding to the configuration of a portion of an organ, a
plurality of the support structures 22 may be positioned in an
organ. The support structures 22 may be positioned adjacent to each
other and/or spaced apart from each other in the organ. Although it
may be desired to position the support structure 22 in an organ,
the support structure may be positioned at other locations in a
patient's body.
[0028] The support structure 22 may be positioned in a patient's
body by fiber optic surgery, such as arthroscopic or laproscopic
surgery. It is contemplated that an imaging apparatus and/or a
robotic mechanism may be used in positioning the support structure.
This may include moving the support structure through a cannula in
the manner disclosed in U.S. patent application Ser. No. 10/102,413
filed Mar. 20, 2002 by Peter M. Bonutti and entitled Methods of
Securing Body Tissue. The implant 20 may be connected with tissue
in a patient's body in any one of the ways disclosed in the
aforementioned application Ser. No. 10/102,413, which is
incorporated herein.
[0029] The support structure 22 may be formed in many different
ways and of many different materials. The specific manner in which
the support structure 22 is formed will be influenced, to some
extent at least, by the location at which the support structure is
to be positioned in the patient's body. In addition, the manner in
which the support structure is formed will depend upon the overall
size of the support structure and whether or not it is to be formed
of biodegradable or nonbiodegradable material.
[0030] The support structure 22 may be integrally formed as one
piece and have a porous construction with openings in which viable
cells 24 are positioned. Alternatively and as shown in FIG. 11, the
support structure may be formed by intertwining one or more strands
(filaments) of a desired material. The viable cells 24 will be
positioned in openings disposed between the intertwined
strands.
[0031] The support structure 22 may be formed of a hydrophilic
material which absorbs body fluid when the support structure 22 is
positioned in a patient's body. When the support structure absorbs
body fluid, it expands and presses against adjacent body tissues to
promote the formation of a mechanical interlock between the support
structure 22 and adjacent body tissues. As the hydrophilic material
of the support structure absorbs liquid from the patient's body,
the volume of the support structure 22 increases. The resulting
expansion of the support structure 22 presses the support structure
against adjacent body tissue. As this occurs, the material of the
support structure 22 and the adjacent tissue are pressed firmly
against each other to form a connection between the support
structure and the adjacent tissues.
[0032] The formation of a mechanical interlock may also be promoted
by compressing the support structure 22 before insertion of the
support structure into the patient's body. When this is done, the
support structure forms a mechanical interlock with tissue due to
the combined effects of absorbing fluid and resiliently
expanding.
[0033] The support structure 22 may be formed of a polymeric
material which absorbs body liquid. The polymeric material may be
either a copolymer or a dipolymer. The polymeric material may be
natural or synthetic collagen. If desired, the polymeric material
may be cellulose, petroylglutamic acid, high purity
carboxymethylcellulose, or polylactide. Of course, the support
structure 22 may be formed of other know material which absorbs
body liquid. The support structure 22 may be formed of materials
disclosed in U.S. Pat. No. 6,152,949 and form an interlock with
adjacent body tissues in the manner disclosed in that patent.
[0034] The implant 20 may be formed as an entire organ or as a
portion of an organ. When this is the situation, the support
structure 22 may be formed by removing an entire organ or a portion
of an organ from a body. The body from which the organ is removed
may be either the patient's body or another body.
[0035] Once the entire organ or portion of an organ has been
removed from a body, cells and/or other tissue may be removed from
the organ to leave a support structure 22 having a configuration
corresponding to the configuration of the organ or portion of an
organ. The support structure 22 may include a collagen matrix
formed by tissue of the organ or portion of an organ removed from a
body.
[0036] Rather than using an organ or a portion of an organ removed
from a body to form the support structure 22, the organ or portion
of an organ may be used as a pattern in the formation of a
synthetic support structure. The synthetic support structure 22 may
be either biodegradable or nonbiodegradable. The synthetic support
structure 22 may be molded or woven to have a configuration
corresponding to the configuration of the organ or portion of an
organ. It is contemplated that the synthetic support structure 22
may have a composite construction and be formed of different
materials which have different characteristics.
[0037] It is contemplated that the viable cells 24 may be any
desired type of viable cells. It is contemplated that the viable
cells 24 may correspond to cells which were in a damaged organ or
other portion of a patient's body. More than one type of viable
cell 24 may be positioned on the same support structure 22. The
support structure 22 and viable cells 24 may be positioned in
either hard or soft tissue.
[0038] When the support structure 22 is to be positioned in an
organ, it is contemplated that the viable cells 24 on the support
structure 22 will have characteristics associated with the
characteristics of normal cells in the organ in which the support
structure is to be positioned. Many organs contain cells which have
different characteristics and perform different functions within
the organ. It is contemplated that the viable cells 24 on the
support structure 22 may have different characteristics
corresponding to the different characteristics of cells of an
organ. When the support structure 22 is to be positioned outside of
an organ, the cells positioned on the support structure may have
any desired characteristic or combination of characteristics.
[0039] It is also contemplated that the viable cells can be
pluripotent cells that are directed to differentiate into the
desired cell type or types. One example of such cells is stem
cells. The differentiation can be controlled by applying or
exposing the cells to certain environmental conditions such as
mechanical forces (static or dynamic), chemical stimuli (e.g. pH),
and/or electromagnetic stimuli.
[0040] More than one type of cell may be positioned on the support
structure 22. The type of cell positioned at a particular location
on the support structure 22 will be determined by the orientation
of the support structure in a patient's body and by the specific
type of tissue desired at a particular location in a patient's
body. For example, stromal cells may be positioned at a location
where foundation tissue is desired and another type of cell may be
positioned at locations where it is desired to have tissue perform
a special function.
[0041] As previously noted, the present invention envisions
harvesting and culturing cells prior to placement within the
support structure 22. Although most researchers tend to isolate and
grow one basic cell line, it may be beneficial to mix multiple
different cell lines together. For example, embryonic cells or
fetal cells can be used to grow cartilage or any desired tissue
(such as liver or pancreas) and these can be combined with the
mature cells of an older individual. The older individual can
either be the patient receiving the mixed cells or possibly another
healthier individual. Regardless of the source, the net result is a
combination of two cell populations, one younger and more vibrant
and another which is older, more mature. The younger cells may have
more of an ability to differentiate into the desired cell type,
while the older cells may have more of the regulatory factors,
tissue inductive factors, etc, which would be more likely to guide
and control the younger cells.
[0042] Growth factors or other therapeutic agents can be added to
either or both of the cell types. The addition of the agents can be
before and/or after combining the cells. Examples of growth factors
that can be used include insulin-like growth factor (IGF-1),
fibroblast growth factor (FGF), transforming growth factor
(TGF-.beta.), hepatocyte growth factor (HGF), platelet-derived
growth factor (PDGF), Indian Hedgehog (Inh) and parathyroid
hormone-related peptide (PTHrP), bone morphogenetic proteins
(BMPs), and Interleukin-1 receptor antagonist (IL-1ra).
[0043] There are many different types of cells which may be
positioned on the support structure 22. These cells include
progenitor cells which differentiate and proliferate to form cells
having desired characteristics; stromal cells which relate to
foundation supporting tissue; and mesenchymal cells which relate to
connective tissues, blood and blood vessels, and other systems.
Fibroblasts may be used in the production of connective tissues.
Osteoblasts may be used in the production of hard tissue (bone).
Myoblasts may be used in the production of muscle.
[0044] Specific cells may be used to provide for growth of tissue
having a function associated with the cell. These cells may include
reticular cells, smooth muscle cells, chondrocytes, retinal cells,
endothelial cells, and other known cells.
[0045] For example, if cardiac tissue is desired, the cells can
include endocardial, myocardial, and pericardial cells. These cells
can be layered or otherwise arranged. If cartilage and bone tissue
is desired, a combination of chondrocytes (and/or chondroblasts)
and osteoblasts, or their precursors can be used.
[0046] One source of precursor cells is bone marrow, which contain
progenitor cells. These progenitor or stem cells can be treated so
as to differentiate into any desired cell type.
[0047] Although the present invention anticipates that the cells
can be harvested in any desired fashion, and are accordingly not
discussed in detail herein, the harvesting of fetal cells deserves
special note. Fetal cells can be harvested directly from the fetus
in situ using minimally invasive techniques or through procedures
such as amniocentesis, chorionic villus sampling (CVS), and other
similar methods that do not involve invasive contact with the
fetus. Regardless of the harvesting method, image guidance (MRI
guidance, ultrasonic guidance, etc) can be used. Computer assisted
techniques can be used in conjunction with the image guidance.
Additionally, the harvesting can be performed using a robotic or
haptic system.
[0048] If desired, specific types of fetal cells such as liver,
pancreas, or renal cells, etc, could be selectively harvested. The
fetus does not necessarily have to be harmed during the harvesting,
but can be kept viable. Thus, the fetus does not have to be aborted
after obtaining the cells, but actually could be left alive and
could be a source for cells possibly through one or multiple
aspirations while the fetus is still growing. For example, one may
require multiple aspirations of liver cells or neural cells, with
multiple cell types at various levels of maturation for the desired
graft.
Implant
[0049] The implant 20 includes the support structure 22 on which
the viable cells 24 are disposed. The viable cells 24 are exposed
to a flow of blood between the blood vessels 32 and 34. The blood
vessels 32 and 34 are connected with the support structure 22. The
blood flows through the blood vessels 32 and 34 in the manner
indicated by arrows in FIGS. 1 and 2.
[0050] It is contemplated that the blood vessels 32 and 34 may be
connected with a support structure 22 in any desired manner. In the
specific embodiment illustrated schematically in FIGS. 1 and 2, an
end portion of the arteriole 32 is stitched to the support
structure 22. Similarly, an end portion of the venule 34 is
stitched to the support structure 22. In addition to being
connected with the blood vessels 28, the implant 20 may be retained
in tissue in a patient's body by stitching the support structure 22
to the tissue in the patient's body.
[0051] It is contemplated that the blood vessels 28 may be
connected with the support structure in many different ways. For
example, the arteriole 32 may be connected with the support
structure 22 by an adhesive such as cyanoacrylate (so-called
"superglue"), Polylatic acid, or fibrin. Additionally, the modified
biofilm discussed below in connection with the attachment of cells
to the support structure 22 can be used to couple the arteriole 32
and the support structure 22. Of course, the end portion of the
venule 34 may be connected with the support structure 22 by an
adhesive in the same manner as in which the arteriole 32 is
connected with the support structure. It should be understood that
the blood vessels 32 and 34 could both be arterioles or venules if
desired.
[0052] To facilitate connecting the arteriole 32 and venule 34 with
the support structure 22, appropriately shaped and sized recesses
may be provided in the support structure 22. These recesses would
have an inside dimension which is only slightly larger than the
outside diameter of the arteriole 32 and/or venule 34. The
arteriole 32, for example, would be telescopically inserted into
the cylindrical recess in the support structure 22. The joint
between the support structure and the exterior surface of the
arteriole 32 may be sealed with a suitable sealant. It is
contemplated that an adhesive could be utilized as the sealant.
[0053] In the embodiment illustrated in FIGS. 1 and 2 the arteriole
32 and venule 34 are shown as being axially aligned with each
other, that is, they are in a coaxial relationship. However, it is
contemplated that the arteriole 32 could be offset to one side, for
example, to the left, and the venule 34 offset to the opposite
side, for example, to the right, of the central axis of the support
structure 32. This would promote a dispersion of the flow of blood
from the arteriole in the support structure 22 before the flow of
blood entered the venule 34. Of course, this would increase the
exposure of the viable cells 24 to the flow of blood.
[0054] If desired, the arteriole 32 could be inserted for a
substantial distance, into the support structure 22 and the venule
34 inserted for a substantial distance into the support structure
22. If this was done, it is contemplated that the arteriole 32
would be offset from the venule 34. Thus, the arteriole 32 could be
offset downward (as viewed in FIG. 2) and the venule 34 offset
upward (as viewed in FIG. 2) so that they are not in axial
alignment with each other.
[0055] By telescopically inserting the arteriole 32 into a
cylindrical recess or hole in the support structure 22 for a
distance which is more than one half of the thickness of the
support structure, the flow of blood would exit the arteriole
adjacent to the side of the support structure from which the venule
34 extends, that is, the right side of the support structure 22 (as
viewed in FIG. 2). Similarly, the venule 34 would extend
telescopically into a recess which extends past the center of the
support structure 22. This would result in the flow of blood in the
support structure 22 entering the venule 34 adjacent to the left
(as viewed in FIG. 2) side of the support structure 22.
[0056] If this was done, the arteriole 32 and venule 34 would not
be axially aligned with each other but would be offset so that the
blood would flow from the arteriole 32 in a reverse direction, that
is toward the left as viewed in FIG. 2, to the entrance to the
venule 34. This would result in the arteriole 32 and venule 34
being disposed in a side-by-side and offset relationship relative
to each other in the support structure 22. The blood would flow
from the end of the arteriole 32 adjacent to the right (as viewed
in FIG. 2) side of the support structure 22 to the end of the
venule 34 adjacent to the left (as viewed in FIG. 2) side of the
support structure. The resulting nonlinear flow of blood between
the arteriole 32 and venule 34 would promote dispersion of the
blood in the support structure 22 and promote exposure of the
viable cells 24 to the flow of blood.
[0057] In the embodiment illustrated in FIGS. 1 and 2 the arteriole
32 and venule 34 are connected directly to the support structure
22. However, it is contemplated that the support structure 22 could
be provided with a pair of conduits which are connected between an
artery and vein in a patient's body. Thus, the support structure 22
may be provided with a tubular conduit in place of the arteriole 32
of FIGS. 1 and 2 and a tubular conduit in place of the venule 34.
The tubular conduit which replaces the arteriole 32 would be
connected with an artery in the patient's body and the tubular
conduit which replaces the venule 34 would be connected with a vein
in the patient's body. The tubular conduits which extend from the
support structure 22 may be formed of a synthetic material or may
be formed by veins and/or arteries harvested from the patient's
body or from another body.
[0058] A plurality of support structures 22 may be implanted into a
patient's body. If this is done, the plurality of support
structures 22 may be interconnected by conduits before being placed
in the patient's body. The plurality of the support structures 22
may be interconnected to have parallel and/or series flow of blood
through the support structures 22.
[0059] It is contemplated that feeder conduits could extend from a
manifold conduit to conduct a flow of blood to each support
structure 22 of a plurality of support structures. If this is done,
a second plurality of feeder conduits may extend from a second
manifold conduit to each of the support structures to conduct a
flow of blood from the plurality of support structures. The first
manifold conduit may be connected in fluid communication with an
artery in a patient's body and the second manifold conduit may be
connected with a vein in a patient's body. This would enable a
plurality of support structures 22 to be supplied with blood
conducted from a single connection between the first manifold
conduit and an artery. Similarly, blood would flow from the
plurality of support structures 22 to a vein through a single
connection between a vein and the second manifold conduit. If
desired, the first and second manifold conduits could both be
connected with either an artery or a vein.
[0060] It is believed that interconnecting a plurality of support
structures 22 with suitable conduits before the support structures
are positioned in a patient's body will facilitate positioning of
the support structures. This is because the number of connections
which have to be made between the support structures 22 and the
blood vessels in the patient's body would be minimized. When a
plurality of support structure are utilized they may be
interconnected in a parallel blood flow arrangement in the manner
previously described or in a series blood flow arrangement before
being positioned in the patient's body.
[0061] It is contemplated that the sides of the support structure
22 may be constructed as to retard a flow of blood from the support
structure. Thus, the support structure 22 may be constructed with
outer side surfaces that effectively block a flow of blood from the
support structure through the outer side surfaces of the support
structure. Alternatively, the outer sides of the support structure
22 may be provided with very small openings which effectively
retard, without completely blocking, a flow of blood through the
sides of the support structure. In another embodiment, the sides of
the support material 22 are made of a material that has one-way
permeability. This would either allow absorption of blood while
preventing discharge, or allow blood discharge while preventing
absorption.
[0062] If the side walls 40 are effective to block the flow of
blood from the support structure 22, all of the blood which enters
the support structure 22 from the arteriole 32 (FIGS. 1 and 2)
would flow from the support structure through the venule 34.
However, if the side walls 40 are somewhat porous so that they are
effective to retard or only partially block a flow of blood through
the side walls 40, a portion of the blood from the arteriole 32
would flow from the support structure 22 through the side walls 40
of the support structure while the remainder of the blood from the
arteriole 32 would flow from the support structure through the
venule 34. By allowing some, but not all, of the blood to flow from
the support structure 22 through the side walls 40, dispersion of
blood within the support structure is promoted.
[0063] It is contemplated that minute passages may be provided in
the support structure 22 to accommodate the growth of capillaries
within the support structure. Thus, a network or web of capillaries
may grow in the support structure 22 between the arteriole 32 and
venule 34. This network of capillaries would facilitate supplying
blood to all of the viable cells 24 within the support structure
22. The side walls 40 (FIG. 1) of the support structure 22 may have
small openings through which capillaries grow between the support
structure and surrounding tissue in the patient's body.
[0064] In the embodiment of the invention illustrated in FIGS. 1
and 2, a single arteriole 32 is connected with a support structure
22 to conduct blood to the support structure and a single venule 34
is connected with the support structure to conduct blood from the
support structure. It is contemplated that a plurality of
arterioles 32 and/or venules 34 may be connected with the support
structure 22. Thus, a plurality of arterioles 32 may be connected
with a first side wall 40 of the support structure 22 to conduct a
flow of blood into the support structure at a plurality of
locations. Similarly, a plurality of venules 34 may be connected
with a second side wall 40 of the support structure 22 at a
plurality of locations to conduct blood from the support structure.
The number of arterioles 32 connected with the support structure 22
may be the same as, greater than, or less than the number of
venules 34 connected with the support structure.
[0065] When it is desired to conduct blood to and from the support
structure 22 along a plurality of flow paths, it is believed that
it may be desired to connect a plurality of conduits with the
support structure before the support structure is positioned in the
patient's body. Thus, at a location remote from an operating room,
a plurality of conduits may be connected with one of the side walls
40 of the support structure 22. These conduits may all be connected
with a single relatively large conduit. This relatively large
conduit would be connected with an artery in a patient's body in an
operating room. Similarly, a plurality of conduits may be connected
with a second side wall of the support structure 22 and be
connected with a second single conduit. This single conduit may be
connected with a vein in a patient's body in an operating room.
This would minimize the number of connections which would have to
be made with the support structure 22 during a surgical procedure
in an operating room and would enable most of the connections to be
made in a less stressful environment remote from the operating
room.
[0066] Tissue inductive growth factors and/or other therapeutic
agents may be provided on the support structure 22 to promote a
growth of tissue between the patient's body and the support
structure 22. The tissue growth inductive factors may promote a
growth of blood vessels, such as capillaries, between tissue and
the patient's body and the support structure 22. The tissue
inductive growth factors may also promote the growth of connective
tissue between the support structure 22 and the tissue in the
patient's body to securely connect the support structure in place
in the patient's body.
[0067] Other additives include materials such as plasticizers,
citrate esters, hexametholsebacate, antibiotics (e.g.,
tetracyclines, penicillins, mefronidazole, clindamycin, etc.), to
prevent infection, etc., or to accomplish other desired conditions
or results. Additional additives or therapeutic agents include
osteoinductive, biocidal, or anti-infection substances. Suitable
osteoinductive substances include, for example, growth factors. The
growth factors may be selected from the group of IGF (insulin-like
growth factors), TGF (transforming growth factors), FGB (fibroblast
growth factors), EGF (epidermal growth factors), BMP (bone
morphogenic proteins), and PDGF (platelet-derived growth
factors).
[0068] The therapeutic agent(s) may be contained within the
material of the support structure 22. Alternatively, the agent(s)
may be disposed in a structure which is separate from the support
structure 22. For example, tissue inductive growth factors could be
disposed in a collagen sponge which is positioned adjacent to the
support structure 22 in the patient's body. Alternatively, the
agent(s) may be positioned in a structure which is connected to the
support structure 22.
[0069] It is believed that it may be advantageous to have a slow
release of the agent(s) adjacent to the patient's body tissue and
the viable cells 24. The agent(s) could be held in a biodegradable
container or containers which degrade over a period of time and
slowly release the agent(s).
[0070] In order to promote the attachment of the viable cells to
the support structure 22, the support structure 22 can be
pretreated with an agent that promotes cell adhesion. One such
agent is an organic substance based on a biofilm. A biofilm is a
slimy, glue-like substance that forms when bacteria attach to
surfaces exposed to water. Typically, colonies of biofilm bacteria
are unwanted as they carry out a variety of detrimental reactions.
However, a sterile biofilm may be used to promote initial
attachment of cells to the support structure 22.
[0071] The sterile biofilm could be engineered to isolate the
glue-like substance while eliminating the adverse properties of the
bacteria. The resulting sterile glue-like substance would be used
to help the cells stick to the support structure 22. The engineered
biofilm could be added to the support structure 22 in the
laboratory that produces the support structure or just prior to the
addition of the cells by the user. Alternatively, the biofilm and
support structure could be combined intra-corporally.
[0072] This biofilm also could be used as an independent
polysaccharide based adhesive with mild to moderate adhesion
forces. The biofilm could serve as a surgical adhesion or grouting
for cells, for tissue fixation (soft tissue to soft tissue, soft
tissue to bone, etc.) and as a sealant.
[0073] In addition to coating the support structure 22, the biofilm
could be used in conjunction with other implants and devices. For
example, the biofilm could be used to coat a stent. Although the
biofilm might degrade in vivo, the coating could serve as a top
coat covering a layer of a therapeutic agent or be impregnated with
the therapeutic agent. Thus, as the coating dissolves, the agent is
delivered locally in a time-released fashion.
[0074] It is contemplated that the support structure 22 may be
formed of a biodegradable material. The biodegradable material
would at least partially degrade after the patient's body tissue
has grown into the support structure 22. The support structure 22
may be formed of a plurality of materials. Some of these materials
may be biodegradable and some of the materials may not be
biodegradable. But by forming the support structure 22 as a
composite of both biodegradable and nonbiodegradable materials, a
portion of the support structure would degrade with passage of time
while another portion of the support structure would remain.
[0075] When the support structure 22 is formed entirely of
biodegradable materials, it is contemplated that portions of the
structure may degrade before other portions. Thus, one portion of
the support structure 22 may be formed of material which degrades
over a relatively long period of time while other portions of the
support structure 22 may be formed of materials which degrade over
a shorter period of time. The provision of tissue inductive growth
factors on the support structure would promote the growth of tissue
into the support structure during the degradation of material of
the support structure.
[0076] It is contemplated that the support structure 22 may be
relatively large and provide for growth of a substantial volume of
tissue in a patient's body. Alternatively, the support structure 22
may be relatively small. If a relatively small support structure 22
is utilized, it is believed that a plurality of the support
structures may be positioned in a patient's body. The individual
support structures of the plurality of support structures may be
positioned adjacent to each other or spaced apart from each
other.
[0077] When the implant 20 is to be positioned relative to the body
tissue, the implant may be moved through a cannula, such as the
expandable cannula disclosed in U.S. Pat. No. 6,338,730, into the
body tissue. An opening for the support structure 22 may be formed
in the body tissue utilizing minimally invasive surgical techniques
similar to those disclosed in U.S. Pat. No. 6,174,313. The surgical
techniques may involve moving one or more devices through an
expandable cannula into the body tissue. The devices moved into the
patient's body may be guided by using magnetic resonance imaging
systems, ultrasonic imaging apparatus, fluoroscopic apparatus
and/or other imaging techniques. The fluoroscopic apparatus may
have a construction similar to that disclosed in U.S. Pat. Nos.
5,099,859; 5,772,594; 6,118,845 and/or 6,198,794. A plurality of
endoscopes may be utilized to generate stereoscopic images, that
is, three dimensional images, of an area where the implant 20 is to
be positioned. The endoscopes and other imaging devices may be
utilized in a manner which is the same as is disclosed in U.S.
patent application Ser. No. 10/102,413 filed Mar. 20, 2002 by Peter
M. Bonutti and entitled Method of Securing Body Tissue.
[0078] During the performance of surgical procedures, a drapery
system which extends between the patient and the surgeon may be
utilized. The drapery system may include a drape which is either
integrally formed as one piece with a surgeon's gown or is formed
separately from the surgeon's gown and is connected with the
surgeon's gown. The drapery system maintains a sterile field which
extends from the surgeon to space adjacent to the patient. This
enables the surgeon to move relative to the patient without
contaminating the sterile field. The drapery system may be
constructed in the manner disclosed in U.S. patent application Ser.
No. 10/263,893 filed Oct. 3, 2002 by Peter M. Bonutti and entitled
Surgical Draping System.
[0079] If a plurality of relatively small support structures 22 are
to be positioned in a patient's body, it is believed that it may be
desired to interconnect the plurality of support structures with a
network of conduits prior to insertion of the support structures
into the patient's body. Thus, a relatively large number of support
structures 22 may be interconnected by a web of conduits. The
resulting mesh or network formed of the plurality of small support
structures 22 and conduits may be loosely positioned over soft
tissue in a patient's body. Each of the support structures 22 may
then be individually implanted or moved into soft body tissue. The
webbing of conduits would extend between the individual support
structures 22. The webbing of conduits would then be connected with
the patient's vascular system.
[0080] By having a relatively large number of small support
structures 22 interconnected by a webbing or network of conduits
before the support structures are positioned relative to a
patient's body, the number of connections to the patient's vascular
system for a relatively large number of support structures would be
minimized. The webbing or network of support structures 22 would be
anchored in the patient's body tissue at each location where a
support structure was implanted. The webbing of conduits would be
effective to conduct a flow of blood to and from the various
support structures 22 in the network.
[0081] As previously discussed, it should be understood that the
viable cells 24 in the plurality of support structures 22
interconnected by the network of blood conduits may be the same
type of cells or different types of cells. It is believed that it
may be particularly advantageous to have different types of cells
in at least some of the support structures 22. For example, one of
the support structures 22 may contain viable endocrine cells and
another support structure may contain viable stromal cells. Still
another support structure may contain viable endothelial cells.
[0082] It should also be understood that a plurality of different
types of cells may be provided in a single support structure 22.
Thus, viable endocrine cells, viable stromal cells, and viable
endothelial cells may all be provided in one support structure 22
of the plurality of support structures interconnected by a network
of conduits which conduct blood to the support structures.
[0083] It is contemplated that the support structure 22 may be
configured so as to provide for the positioning of a layer of
viable cells 28 in a patient's body. The viable cells may be
allograft mesenchymal cells and/or stem cells.
Blood Flow
[0084] In the embodiment of the invention illustrated in FIGS. 1
and 2, the flow of blood is conducted from the arteriole 32 to the
support structure 22 and from the support structure to the venule
34. The support structure 22 contains a matrix of viable cells 24
(FIG. 2). In the embodiment of the invention illustrated in FIG. 3,
blood flow within the support structure 22 is controlled to
maximize the exposure of the viable cells 24 to the flow of
blood.
[0085] In the embodiment of the invention illustrated in FIG. 3, an
implant 20 includes a support structure 22. Blood vessels 28 are
connected with the support structure 22. The blood vessels 28
include an arteriole 32 and a venule 34. In the embodiment of FIG.
3, the arteriole 32 and venule 34 are connected to the same side
wall 40 of the implant 20. In order to maximize exposure of the
viable cells 24 to a flow of blood, a barrier 48 (FIG. 3) is
provided in the support structure 22. The barrier 48 is effective
to direct the flow of blood in the support structure 22. The
barrier 48 may extend between and be connected with opposite side
walls 40 of the support structure 22. Alternatively, the barrier 48
may be spaced from the side walls of the support structure.
[0086] It is contemplated that the barrier 48 may be formed of
either a material which is impervious to a flow of blood or a
material having small openings through which blood can flow. If the
barrier 48 is provided with small openings through which blood can
flow, the openings would be small enough to retard a flow of blood
through the barrier. It is contemplated that barrier 48 may be
integrally formed as one piece with a support structure 22 or
formed separately from the support structure and mounted in the
support structure.
[0087] The flow of blood from the arteriole 32 cannot readily move
upward (as viewed in FIG. 3) through the barrier 48. Therefore, the
blood will flow downward towards the viable cells 24 in the lower
portion of the support structure 22. The blood from the arteriole
32 will subsequently flow upward from the lower portion of the
support structure toward the upper portion of the support
structure. When the blood is has moved around the right (as viewed
in FIG. 3) end of the barrier 48, the blood can flow upward through
the upper portion of the support structure 22. The upper portion of
the support structure 22 is connected with the venule 34 which
conducts the flow of blood from the support structure 22 to a
vein.
[0088] With the specific arrangement of the barrier 48, arteriole
32 and venule 34 illustrated in FIG. 3, it is believed that it
would be desired to form the lower side wall 40 of the support
structure 22 of a material which blocks or at least substantially
blocks a flow of blood. It may also be desired to have the upright
(as viewed in FIG. 3) side walls 40 of the retainer of support
structure 22 formed of a material which blocks or at least
partially blocks a flow of blood. This construction would tend to
promote the flow of blood from the lower portion of the support
structure 22 to the upper portion of the support structure.
[0089] It is contemplated that the barrier 48 may be constructed of
a plurality of members which are either interconnected or spaced
apart to cause the blood to flow along a convoluted path between
the arteriole 32 and venule 34 of FIG. 3. The barrier 48 may be
constructed with a plurality of bends which cause the blood to flow
from the arteriole 32 through a maze in the support structure 22 to
promote the flow of blood past each of the viable cells 24. When
the barrier 48 has such an extended irregular configuration, it may
be desired to form the barrier 48 of a material through which the
blood can flow between various turns and passages in the maze
formed within the support structure 22. With a passage of time, it
is believed that capillaries may tend to grow in micron size
passages in the support structure 22.
[0090] In the embodiments of the invention illustrated in FIGS.
1-3, the support structure 22 has been illustrated as having a
polygonal configuration, specifically a rectangular configuration.
However, it is contemplated the support structure 22 could have a
different configuration if desired. For example, rather than the
cubicle configuration illustrated in FIGS. 1-3, the support
structure could have a configuration of a polyhedron with generally
flat sides. Alternatively, the support structure 22 could have a
spherical, oval, or ovoid configuration. The specific configuration
of the support structure 22 is a function, in part at least, of a
location where the support structure is to be positioned in a
patient's body. Of course, the configuration of the side walls 40
of the support structure 22 will have an influence on the
configuration on the barrier 48. It should be understood that the
barrier 48 may have an arcuate configuration and may be formed as a
portion of a sphere or cylinder.
Alternative Implant
[0091] In the embodiments of the invention illustrated in FIGS.
1-3, the same number of conduits are utilized to conduct blood to
the implant as are used to conduct blood from the implant. Thus, a
single arteriole 32 and a single venule 34 are connected with a
support structure 22 which has a relatively simple cubicle
construction. A simple one piece barrier 48 has been illustrated in
FIG. 3 to direct a flow of blood within the support structure
22.
[0092] In the embodiment of the invention illustrated in FIG. 4,
the number of conduits utilized to conduct blood to the implant is
different than the number of conduits utilized to conduct blood
from the implant. In addition, the implant 20 has a complex
configuration formed by flat and arcuate surfaces. A multi-piece
barrier is provided in the implant to direct the flow of blood.
[0093] In the embodiment of the implant 20 illustrated in FIG. 4, a
single arteriole 32 conducts a flow of blood to the support
structure 22. A plurality of venules 34 conduct the flow of blood
from the support structure 22. Although only two venules 34 have
been illustrated in FIG. 4, it should be understood that a greater
number of venules may be provided if desired. Of course, a greater
number of arterioles 32 could also be connected with the support
structure 22 if desired. The number of arterioles 32 may exceed the
number of venules 34 if desired.
[0094] A plurality of viable cells 24 are provided within the
support structure 22. A barrier 48 is provided within the support
structure 22. In the embodiment of the invention illustrated in
FIG. 4, the barrier 48 is formed of a plurality of pieces or
sections. One section 56 of the barrier 48 has a generally conical
configuration. However, the section 56 of the barrier 48 has an
open left (as viewed in FIG. 4) end portion to enable blood from
the arteriole 32 to flow through the leftward end portion of the
generally conical section 56 of the barrier. In addition, the
barrier 48 includes a flow splitter 58 which disperses a flow of
blood entering the open left (as viewed in FIG. 4) end of the
conical section 56 of the barrier. The flow splitter section 58 of
the barrier may be formed by a plurality of pieces or by a single
piece. The flow splitter section 58 may be aligned with the opening
in the left end of the barrier 48 or may be offset relative to the
opening. For example, the splitter section 58 could be formed by a
plurality of spaced apart sections each of which is offset slightly
from the central axis of the opening formed in the left (as viewed
in FIG. 4) end portion of the section 56 of the barrier 48.
[0095] It should be understood that the arteriole 32 and venules 34
may be connected with the support structure 22 of FIG. 4 in any one
of the manners previously discussed herein. Rather than connecting
an arteriole 32 and venules 34 with the implant 20 as it is
positioned in the patient's body, conduits may extend from the
support structure 22 and be connected with one or more arteries
and/or one or more veins in the patient's body. It should be
understood that either a greater or lesser number of arterioles 32
and/or venules 34 may be connected with the support structure 22.
The arterioles 32 and venules 34 may be connected with the support
structure in any one of the manners previously mentioned
herein.
Organ Implant
[0096] It is contemplated that the implant 20 of FIGS. 1-4 may be
positioned in either soft or hard tissue in a patient's body. It is
believed that it may be desired to position one or more of the
implants 20 in an organ in a patient's body. If this is done, the
implant may be provided with one or more side walls 40 having a
configuration which corresponds to a configuration of the exterior
surface of the organ.
[0097] Although it is contemplated that the implants 20 of FIGS.
1-4 could be utilized in association of any one of the many
different organs in a patient's body, the implants are described in
conjunction with a kidney 66 (FIG. 5) disposed in the patient's
body. It should be understood that the kidney 66 is only an example
of one specific organ, that is, a functional unit of cells, with
which the implants of FIGS. 1-4 may be associated.
[0098] The kidney 66 has a renal artery 68 through which blood is
conducted to the kidney. In addition, the kidney 66 has a renal
vein 70 through which blood is conducted from the kidney. A ureter
72 conducts urine from the kidney 66 to the patient's bladder. The
renal artery 68, renal vein 70 and ureter 72 are connected with a
renal capsule 74.
[0099] When a kidney 66 becomes damaged by trauma and/or disease,
it may be desired to rejuvenate the kidney through the use of one
or more implants corresponding to the implants 20 of FIGS. 1-4. The
implants 20 may be positioned in a spaced apart relationship in the
kidney 66 or positioned adjacent to each other. The specific
location and arrangement of the implants 20 in the kidney 66 will
depend upon the extent and type of damage which the kidney has
incurred.
[0100] The size and number of the implants positioned in the kidney
66, as well as their location in the kidney can be varied in the
manner believed to be the best remedy for damage to the kidney. For
example, a plurality of the implants 20 (FIGS. 1-4) may be
positioned at spaced apart locations in the kidney 66 (FIG. 6).
Alternatively, the plurality of the implants 20 may be positioned
in engagement with each other at selected locations in the kidney
66. Since the implants 20 are relatively small, the locations where
they are positioned in the kidney 66 can be selected to best
compensate for the damage incurred by the kidney.
[0101] When a single implant 20 is to be positioned in the kidney,
the implant may be connected with blood vessels in the kidney in
the manner previously described in conjunction with FIGS. 1-4
herein. Alternatively, a plurality of the implants 20 may be
connected in series with each other so that blood flows from one
implant to the next succeeding implant. As was previously mentioned
herein, the implants 20 may be connected in parallel with each
other and with an artery which supplies blood to the implants and a
vein which receives the blood from the implants. As was also
previously mentioned, the implants 20 may be associated with any
desired organ in the patient's body. The kidney 66 of FIGS. 5 and 6
is only representative of many organs in a patient's body.
[0102] When an implant 20 is to be positioned in the kidney 66, a
recess or opening having a configuration corresponding to the
configuration of the implant is cut into the kidney. The implant 20
is then connected with blood vessels in the kidney 66 and is
positioned in the opening (FIG. 6). The opening may be sized so as
to accept a single implant 20 or a plurality of implants. If the
opening is sized to accept a single implant 20, the size of the
single implant may be either relatively small or relatively large
depending upon the damage which has been occurred by the
kidney.
[0103] Under certain circumstances, it is believed that it may be
desired to remove a section, that is a relatively large piece of a
kidney. When this has been done, a single implant 20 having a
configuration corresponding to the configuration of the removed
section of the kidney may be implanted at the location where the
section was removed from the kidney. Since the relatively large
implant 20 has the same configuration as the exterior surface of
the kidney, when tissue grows into the implant, the implant will
form a portion of the kidney having the same configuration as the
section which was removed from the kidney.
[0104] When one or more implants 20 are to be positioned in the
kidney 66, the viable cells 24 may include renal cells having
characteristics of replaced cells in the kidney. Some of the viable
cells in the implants 20 may be stromal cells and/or fibroblast.
Depending upon the location where the implants 20 are positioned in
the kidney, some of the viable cells 24 may be endothelial cells.
Thus, stromal cells, renal cells, and endothelial cells may be
positioned on a single implant 20 which is connected with the
kidney 66. Of course, other types of cells may be positioned on the
implant if desired.
[0105] Although the implants 20 have been illustrated in FIG. 6 as
being positioned in the kidney 66, it is contemplated that the
implants 20 may be positioned in a different organ if desired. For
example, the implants 20 may be positioned in a patient's heart or
one or more of the bones of the patient's skeleton. It is
contemplated that the implants 20 may be used for applications
other than partial or total organ replacement. Thus, the implant 20
may be located at any desired location in either hard or soft
tissue in the patient's body.
Organ Replacement
[0106] It is contemplated that it may be desired to replace an
entire organ rather than a portion of the organ. When an organ is
to be replaced, a support structure 22 having a configuration
corresponding to the configuration the organ to be replaced is
formed. This support structure 22 may be naturally formed or
synthetically formed. The organ to be replaced may be any one of
the organs in the patient's body.
[0107] Assuming that the kidney 66 is the organ in a patient's body
to be replaced, it may be desired to form a support structure
having a configuration corresponding to the configuration of the
kidney 66. When it is desired to utilize a naturally formed support
structure having the configuration of a kidney, a kidney 66 is
obtained from a body. The kidney 66 may be obtained from a
patient's own body, from the body of another living human, from a
cadaver (dead human body), or from a living or dead animal.
[0108] When a kidney is used to form the support structure, it may
be desired to render the organ non-antigenic. Accordingly, any
living cells on a kidney 66 removed from a living donor may be
killed with a cytotoxic solution, such as a strong saline solution.
Alternatively, the living cells may be killed by radiation. Of
course, other methods could be utilized to kill the living
cells.
[0109] Assuming that the kidney 66 is to be obtained from a
cadaver, the renal artery 68, renal vein 70 and ureter 72 are
severed and the kidney 66 is removed from the cadaver. Dead cells
and/or other tissue are removed from the cadaver kidney to leave a
collagen matrix having a configuration corresponding to the
configuration of the kidney in the cadaver. The collagen matrix may
have a relatively large portion with a configuration corresponding
to the configuration of the renal capsule 74 (FIG. 5), and three
tubular conduits corresponding to the renal artery 68, renal vein
70 and ureter 72.
[0110] The collagen matrix is utilized as a support structure 22
for viable cells, corresponding to the viable cells 24 of FIGS.
1-4. It is contemplated that the viable cells 24 will be different
types of cells and will be placed at various locations in the
collagen matrix forming the support structure 22 made from the
cadaver kidney. For example, renal cells may be positioned in the
portion of the collagen matrix formed by the cadaver kidney
corresponding to the renal capsule 74. Endothelial cells may also
be positioned on the portion of the collagen matrix corresponding
to the renal capsule 74 and on the portions of the collagen matrix
corresponding to the renal artery 68, renal vein 70 and ureter 72.
In addition, stromal cells may be positioned on the portion of the
collagen matrix corresponding to the renal capsule 74, renal artery
68, renal vein 70 and ureter 72. Fibroblast and mesenchymal cells
may also be placed on the support structure 22 formed from the
cadaver kidney. In addition, materials for promoting growth of
tissue may be positioned on the support structure.
[0111] Once the viable cells 24 have been positioned on the
collagen matrix support structure 22 formed from the cadaver
kidney, the result is a replacement kidney 66. The replacement
kidney 66 may be formed at a location spaced from an operating
room. After the replacement kidney 66 has been formed, it may be
transported to the operating room and implanted in the patient.
[0112] To implant the replacement kidney 66 in the patient, the
damaged kidney in the patient is removed. Removal of the damaged
kidney 66 from the patient would involve severing the renal artery
68, renal vein 70 and ureter 72 connected with the damaged kidney
in the patient.
[0113] After the damaged kidney 66 has been removed from the
patient, the renal artery 68 of the replacement kidney is connected
with the portion of the renal artery remaining in the patient's
body. Similarly, the renal vein 70 of the replacement kidney 66 is
connected with the portion of the renal vein remaining in the
patient's body. In addition, the ureter 72 on the replacement
kidney 66 is connected with the portion of the ureter remaining in
the patient's body. The replacement kidney 66 is then moved to a
desired location in the patient's body.
[0114] Blood is conducted to the replacement kidney 66 through the
remaining portion of the patient's renal artery 70 and the portion
of the renal artery associated with the replacement kidney. Blood
is conducted from the replacement kidney 66 through the portion of
the renal vein 70 associated with the replacement kidney and the
remaining portion of the patient's renal vein. Urine is conducted
from the replacement kidney 66 through the portion of the ureter 72
associated with the replacement kidney and to the remaining portion
of the patient's ureter.
[0115] Although the foregoing description has related to
replacement of a kidney 66, the method described herein may be used
in association with the replacement of the other organs in a
patient's body. Thus, the method described herein may be used in
conjunction with the replacement of an adrenal gland, heart, liver,
bone, pancreas, or other organ.
[0116] Rather than utilizing the collagen matrix of the cadaver
kidney to at least partially form the support structure for a
replacement kidney, the cadaver kidney may be utilized as a pattern
to form a mold cavity having a configuration corresponding to the
configuration of the cadaver kidney. Thus, the cadaver kidney 66
(FIG. 7) may be enclosed with mold material 80. The mold material
may be divided into two segments 82 and 84 (FIG. 7). The pattern 66
is enclosed by the mold material 80 and the mold material is
solidified around the pattern to form the two segments 82 and
84.
[0117] Once the mold material has solidified around the kidney
pattern 66, the kidney pattern is separated from the mold. Once the
kidney pattern 66 has been separated from the mold 62, the two
segments 82 and 84 may be interconnected to form a mold assembly
which defines a recess or cavity 88. The recess or cavity 88 has a
configuration which corresponds to the configuration of the pattern
kidney along with the attached portions of the renal artery 68,
renal vein 70, and ureter 72.
[0118] The kidney pattern 66 may be obtained from a patient, from
another living human, from a cadaver, or from an animal. It is
believed that it may be preferred not to use the patient's own
kidney as the kidney pattern 66 since the configuration of the
patient's own kidney may be unsuitable. If desired, an artificial
pattern, having a configuration corresponding to a desired
configuration of a kidney may be used as a pattern for the mold
cavity 88.
[0119] Once the mold cavity 88 has been formed by separating the
mold segments 82 and 84 from the natural or artificial kidney
pattern 66, a synthetic support structure 22 is formed in the mold
cavity 88. This may be accomplished by injecting a material into
the recess or cavity 88 while the two mold segments 82 and 84 are
interconnected. The material injected into the mold cavity 88 may
be either biodegradable or nonbiodegradable. The material injected
into the mold cavity 88 solidifies with an open cell porous
structure. Synthetic collagen or polylatic acid with a chemical
blowing agent or entrained gas may be utilized to form the porous
support structure.
[0120] When the material injected into the mold cavity has
solidified with an open cell porous structure, it will have a
configuration corresponding to the configuration of the renal
capsule 74 of the kidney pattern 66, the renal artery 68, renal
vein 70 and ureter 72 connected with the renal capsule of the
kidney pattern. The resulting support structure 22 is formed as one
piece of porous material.
[0121] The selected viable cells, corresponding to viable cells 24
(FIGS. 1-4), are positioned in small openings or pores of the cast
porous support structure 22 having the configuration of a kidney.
It is contemplated that the viable cells 24 may be positioned in
any one of many different known ways on the porous support
structure 22 having the configuration of a kidney. One way in which
the viable cells may be positioned on the porous support structure
22 is to inject a liquid solution containing the viable cells 24
into the porous support structure 22. The viable cells 24 would be
the deposited in the porous of the support structure 22 as the
liquid dries. A different solution with different viable cells may
be injected in different portions of the porous support structure
22. The viable cells 24 may be any of the viable cells previously
mentioned herein. Of course, the viable cells 24 would be deposited
on the porous support structure 22 in accordance with the desired
tissue structure to be obtained by growth of the viable cells.
Other known methods of positioning viable cells on a support
structure may be utilized if desired.
[0122] Rather than forming a support structure 22 for the synthetic
replacement organ of a porous material, it is contemplated that the
support structure may be formed of intertwined strands or filaments
(FIG. 11). The strands or filaments may be woven together in the
recess or cavity 88 formed by the mold segments 82 and 84. This
would result in the intertwined filaments or strands having an
overall configuration corresponding to the configuration of the
pattern kidney 66 of FIG. 7.
[0123] The intertwined strands or filaments would define relatively
small spaces in which the viable cells 24 would be positioned. The
viable cells 24 may be positioned on the woven support structure by
injecting a solution containing the viable cells into the spaces or
recesses formed by the intertwined strands of the support
structure. Of course, different types of viable cells 24 would be
positioned at different locations in the woven support structure.
Any one of the desired types of viable cells 24 previously
mentioned herein may be utilized. It should be understood that the
specific viable cells 24 positioned at a specific location on the
woven support structure 22 would depend upon the desired
characteristics of the tissue to be grown at that location.
[0124] The strands of the woven support structure 22 may be either
a naturally occurring materials or synthetic materials. The strands
of the woven support structure 22 may be biodegradable or
nonbiodegradable. It is contemplated that strands of synthetic or
natural collagen may be utilized to form the woven support
structure 22 on which the viable cells 24 are positioned. If
desired, the exterior of the woven support structure 22 may be
sealed by encapsulating the woven support structure with a material
through which blood cannot easily flow. The material used to
encapsulate the woven support structure may be either biodegradable
or nonbiodegradable. It is contemplated that a suitable polymeric
material, such as polylatic acid, may be utilized. It is believed
that blood vessels, such as capillaries, will grow through small
passages or channels formed in the woven support structure.
[0125] The foregoing description has been a conjunction with the
replacement of a kidney 66 in a patient. It is contemplated that
the procedures previously described herein could be utilized in
conjunction with a replacement of many different types of organs.
For example, a patient's pancreas may be replaced. If the patient's
pancreas is replaced, viable endocrine cells and viable exocrine
cells may be positioned on the support structure 22. In addition,
islets of Langerhans could be positioned on the support
structure.
[0126] It is contemplated that the entire pancreas or only a
portion of the pancreas may be replaced. If desired, relatively
small implants, corresponding to the implants 20 of FIGS. 1-4, may
be positioned in the pancreas. The specific types of viable cells,
that is islets of Langerhans, endocrine, and/or exocrine cells
would be positioned at the location on the support structure 20
where the corresponding tissues are to be grown.
[0127] It is contemplated that a portion of the patient's hard
tissue (bone) may be replaced using the foregoing methods. If this
is to be done, a support structure 22 having a configuration
corresponding to a configuration of at least a portion of one of
the bones in the patient's skeleton would be replaced. The viable
cells 24 positioned on the support structure 22 may be osteoblasts
and/or mesodermal cells. In addition, osteochondral cells may be
positioned on the support structure 22. Myoblasts may be utilized
in association with the support structure 22 to promote the growth
of muscular tissue.
Partial Replacement of an Organ
[0128] Rather than replacing an entire organ, it is contemplated
that a portion of an organ may be replaced. In FIG. 8, a segment of
a blood vessel 96 is to be replaced. However, it should be
understood that the method of the present invention may be used to
replace portions of an organ other than a blood vessel. The segment
of the blood vessel 96 has been selected to be representative of a
portion of many different organs in a patient's body.
[0129] When a segment of a blood vessel 96 is to be replaced, it is
believed that the blood vessel will be severed at cuts 98 and 100
disposed at spaced apart locations along the length of the blood
vessel. The portion of the patient's blood vessel between the cuts
98 and 100 is removed. An implant 104 is positioned between the
cuts and connected with segments 106 and 108 of the blood vessel
96. The implant 104 is tubular and has a cylindrical
configuration.
[0130] The implant 104 includes a cylindrical support structure 112
having the same general construction as the support structure 22 of
FIGS. 1-4. The support structure 112 has a plurality of openings or
recesses in which viable cells 114 are disposed. In the embodiment
of FIG. 8, the support structure 112 is enclosed by an outer layer
116 which blocks a radially outward flow of blood from the inside
of the tubular cylindrical implant 104.
[0131] The segments 106 and 108 of the blood vessel 96 may be
connected with the support structure 112 by stitching or by
adhesive. Of course, the support structure 112 could be connected
with the segments 106 and 108 of the blood vessel 96 in a different
manner if desired.
[0132] It is contemplated that the viable cells 114 may include
endothelial cells, mesenchymal cells, and/or smooth muscle cells.
It should be understood that more than one type of cell may be
mounted on the support structure 112. Tissue growth induction
materials may be provided on the support structure 112 to promote a
growth of tissue between the segments 106 and 108 of the blood
vessel 96 and the support structure 112. During a flow of blood
through the blood vessel 96, the viable cells 114 on the support
structure 112 are exposed to the flow of blood.
[0133] If the blood vessel 96 is a vein, it may be desired to
provide a check valve in association with the implant 104. The
check valve may be formed by flexible flaps which are pressed
against each other to prevent a back flow of blood in much the same
way as in naturally occurring veins. The check valve may be formed
by flaps of synthetic material or of a matrix of collagen or other
materials in which viable smooth muscle cells are disposed. If
viable smooth muscle cells are provided on flaps formed of a
support structure of natural or synthetic collagen or other
material, viable smooth muscle cells on the support structure 112
and the smooth muscle cells on the check valve may grow together to
provide a check valve having the same general construction as a
naturally occurring check valve in a vein or other organ.
[0134] Rather than being connected with a segment of a blood
vessel, one end of the implant 104 may be connected with another
organ, such as a heart. Thus, the patient's blood vessel may be
severed adjacent to the heart. The segment 106 of the blood vessel
would be connected with one axial end portion of the support
structure 112 of the implant 104. The opposite axial end portion of
the tubular cylindrical implant 104 would be connected directly
with the patient's heart. Of course, the implant 104 could be
associated with organs other than a patient's heart. It should also
be understood that the implant 104 may be positioned in a blood
vessel at a location remote from other organs.
[0135] During connection of the segments 106 and 108 of the blood
vessel 96 with the implant 104, it may be advantageous to utilize
an expandable member 122 to align the segments 106 and 108 of the
blood vessel 96 with the implant 104 in the manner illustrated
schematically in FIG. 9. When the expandable member 122 is in a
contracted condition, it is inserted through a relatively small
slit in the segment 108 of the blood vessel 96 at a location remote
from the cuts 98 and 100 where the implant 104 is to be positioned.
The expandable member 122 is moved axially along the blood vessel
96 to a location adjacent to the cut 100. While the expandable
member is in a contracted condition, it is moved from the segment
108 of the blood vessel 96 into the implant 104. The leading end
portion of the expandable member 122 is then moved from the implant
104 into the segment 106 of the blood vessel 96.
[0136] Once the expandable member has been positioned so that it
extends between the segments 106 and 108 of the blood vessel 96 and
through the implant 104 (as shown in FIG. 9), the expandable member
is expanded. As the expandable member 122 is expanded, the end
portions of the segments 106 and 108 of the blood vessel 96
adjacent to the implant are expanded and moved into alignment with
the implant 104. As the expandable member 122 expands radially
outward from a contracted condition to the expanded condition
illustrated schematically in FIG. 9, a collapsed or contracted end
portion of the segment 106 of the blood vessel 96 adjacent to the
cut 98 is expanded. As this occurs, the end portion of the blood
vessel segment 106 adjacent to the cut 98 moves radially outward
and is aligned with an adjacent end portion of the cylindrical
tubular implant 104. At the same time, the opposite end portion of
the expandable member 122 is expanded. As this occurs, the end
portion of the segment 108 of the blood vessel 96 adjacent to the
cut 100 is expanded. Thus, the end portion of the blood vessel 108
is expanded from a collapsed or contracted condition to the
expanded condition illustrated in FIG. 9 by expansion of the
expandable member 122.
[0137] As the expandable member 122 expands, a central portion of
the expandable member, that is a portion of the expandable member
enclosed by the implant 104, expands into engagement with an inner
side surface of the implant 104. As this occurs, annular axially
opposite ends of the implant 104 are aligned with the cuts 98 and
100 on the ends of the blood vessel segments 106 and 108.
[0138] While the blood vessel segments 106 and 108 are aligned with
the implant 104, the cut 98 on the end portion of the blood vessel
106 is connected to the annular end portion of the implant 104. The
segment 106 of the blood vessel 96 may be connected with the
implant 104 by stitching, by suitable adhesive, or by other known
methods. Similarly, the cut 100 on the end portion of the segment
108 of the blood vessel 96 is connected to the implant 104 by
stitching, a suitable adhesive, or other known methods.
[0139] Once the blood vessel segments 106 and 108 have been
connected with the implant 104, the expandable member 122 is
contracted. The contracted expandable member 122 is then pulled out
of the blood vessel 96 through the same small opening through which
the contracted expandable member was moved into the blood
vessel.
[0140] The expandable member 122 may be expanded by a mechanical
device or by fluid pressure. Thus, the expandable member may have a
device which expands through a mechanical action in a manner
similar to that disclosed in U.S. Pat. No. 5,685,826.
Alternatively, the expandable member 122 may be expanded under the
influence of fluid pressure in the manner similar to that disclosed
in U.S. Pat. No. 6,358,266. The expandable member 122 may be
expanded in the manner similar to that disclosed in U.S. Pat. No.
6,338,730.
[0141] Although it is believed that many different types of known
expandable devices may be utilized for the expandable member 122,
the expandable member may be a balloon which is expanded under the
influence of either gas or liquid pressure. The gas or liquid
pressure may be conducted to the balloon through a conduit 128
(FIG. 9). The conduit 128 may have sufficient rigidity so as to be
able to move the expandable member 122, specifically, a balloon,
along the blood vessel 96 and through the implant 104 to the
position illustrated schematically in FIG. 9 while the expandable
member is in a contracted condition.
[0142] Once the expandable member has been expanded, under the
influence of fluid pressure conducted through the conduit 128, the
implant 104 and segments 106 and 108 of the blood vessel 96 are
interconnected. The fluid is then exhausted from the expandable
member 122 through the conduit 128 to contract the expandable
member. The contracted expandable member is then pulled out of the
blood vessel 96 under the influence of force transmitted through
the conduit 128.
[0143] Rather than using a single expandable member 122, a
plurality of expandable members 134 and 136 (FIG. 10) may be
utilized to align the implants 104 and the end portions 106 and 108
of the blood vessel 96. The members 134 and 136 may be expanded by
mechanical mechanisms or may be expanded under the influence of
fluid pressure in the manner previously explained in conjunction
with the expandable member 122 of FIG. 9.
[0144] The expandable member 134 is inserted into the segment 106
of the blood vessel 96 when the expandable member is in a
contracted condition. The contracted expandable member 134 is
inserted through a small slit formed in the blood vessel 106 at a
location spaced from the cut 98. The contracted expandable member
134 is pushed along the segment 106 of the blood vessel by a
conduit 140 connected with the contracted expandable member 134.
The leading end portion of the contracted expandable member 134 is
moved from the segment 106 of the blood vessel 96 into the implant
104.
[0145] Similarly, the contracted expandable member 136 is moved
into the segment 108 of the blood vessel 96 through a small slit at
a location spaced from the cut 100. The contracted expandable
member 136 is pushed along the segment 108 of the blood vessel 96
by a conduit 144. The leading end portion of the contracted
expandable member 136 is moved from the segment 108 of the blood
vessel 96 into the implant 104.
[0146] After both of the contracted expandable members 134 and 136
have been position with their leading end portions in the implant
104, they are expanded. Expansion of the expandable member 134
expands the end portion of the blood vessel segment 106 and moves
it into alignment with the adjacent end portions of the implant
104. Similarly, expansion of the expandable member 136 expands the
end portion of the blood vessel segment 108 and moves it into
alignment with the end portion of the implant 104. This results in
the implant 104 and the segments 106 and 108 of the blood vessel 96
being held in axial alignment with each other, in the manner
illustrated schematically in FIG. 10, by the expanded expandable
members 134 and 136.
[0147] While the implant 104 and segments 106 and 108 of the blood
vessel 96 are held in alignment by the expanded expandable members
134 and 136, the end portions of the segments of the blood vessel
are connected with the implant 104. Thus, the annular cut end 98 of
the segment 106 to the blood vessel 96 is connected to one annular
end of the implant 104. The annular cut end 100 of the blood vessel
segment 108 is connected to the opposite annular end of the implant
104. The blood vessel segments 106 and 108 may be connected with
the implant 104 by stitches, a suitable adhesive, or another known
manner.
[0148] Once the blood vessel segments 106 and 108 have been
connected with the implant 104, the expandable members 134 and 136
are contracted. The contracted expandable members 134 and 136 are
then pulled from the blood vessel segments 106 and 108 through the
small slits which they enter the blood vessel segments.
[0149] Although the expandable members 134 and 136 may be
mechanically expandable members, it is believed that it may be
preferred to expand the expandable members under the influence of
fluid pressure, that is under the influence of pressure transmitted
through either a gas or a liquid. The fluid pressure is conducted
to the expandable members 134 and 136 through the conduits 140 and
144.
[0150] In the embodiment of the invention illustrated in FIGS. 9
and 10, the expandable members 122, 134 and 136 are illustrated in
conjunction with the connecting of segments 106 and 108 with a
blood vessel 96 with an implant 104. However, it is contemplated
that implant 104 could be connected directly with an organ, such as
a heart. For example, if the left (as viewed in FIG. 9) end of the
implant 104 is to be connected with a heart, the segment 106 of the
blood vessel 96 would be omitted and the left or leading end
portion of the balloon 122 (FIG. 9) inserted into an opening formed
in the heart. This would align the implant 104 with the opening in
the heart. The implant 104 would then be connected directly to the
heart with a suitable adhesive, stitching or other known device.
The segment 108 of the blood vessel 96 would then be connected with
the implant 104 while the expandable member 122 maintains the
segment 108 of the blood vessel 96 in alignment with the implant
104.
[0151] Although the expandable members 122, 134 and 136 have
previously been described herein in conjunction with the connecting
of an implant 104 with at least one of the blood vessel segments
106 and/or 108, it is contemplated that the expandable members may
be utilized in the positioning many different types of implants
relative to many different types of tissue. For example, expandable
members similar to expandable members 122, 134 and 136 may be
utilized in conjunction with the connection of ducts with organs or
with implanting of a segment in a duct. Alternatively, expandable
members, similar to the expandable members 122, 134 and 136, may be
utilized during the connection of an implant in a portion of a
patient's intestine or during the connection of an implant with one
end of an intestine and a stomach.
[0152] It is contemplated that an implant may be positioned in a
bone in a patient's body using expandable members similar to the
expandable members 122, 134 and 136. This may be done by inserting
an expandable member through an opening in the implant. The
expandable member would extend from the implant into the bone to
align the bone with the implant. Once the bone and the implant have
been interconnected the expandable member would be withdrawn from
the opening through which it was inserted into the implant. Once
this has been accomplished, the interior of the bone may be filled
with an artificial cancellous bone or with a slurry containing
osteoblast and bone growth promoting materials.
Conclusion
[0153] In view of the foregoing description, it is apparent that
the present invention provides a method of implanting viable cells
24 into a body of a patient. The viable cells 24 may be positioned
on a support structure 22. One or more blood vessels 28 in a
patient's body may be connected with the support structure 22 at
one or more locations. The viable cells 24 on the support structure
22 may be exposed to blood flow in the support structure. One or
more support structures 22 may be provided and positioned in the
patient's body.
[0154] The support structure 22 may be formed in many different
ways. One way in which the support structure 22 may be formed is by
removing an organ 66 or a portion of an organ from a body, either
the patient's own body or another body. Cells and/or other tissue
may be removed from the organ 66 or portion of the organ to leave a
support structure 22 having a configuration corresponding to the
configuration of the organ or portion of an organ. Viable cells 24
are positioned on the support structure 22. The support structure
22, which has a configuration corresponding to the configuration of
an organ 66 or portion of an organ, is positioned in the patient's
body with the viable cells 24 disposed on the support structure 22.
Blood vessels 28 may advantageously be connected with the support
structure 22 as it is positioned in the patient's body. The support
structure 22 may correspond to an entire organ 66 or only a portion
of an organ.
[0155] The support structure 22 may be formed by using an organ 66
or portion of an organ from a body, that is either the patient's
body or another body, as a pattern. Alternatively, the pattern may
be synthetically constructed to have a configuration corresponding
to the general configuration of an organ 66 or portion of an organ
in a patient's body. The pattern is at least partially enclosed
with mold material 80. The pattern and mold material are
subsequently separated to leave a mold cavity 88. The synthetic
support structure 22 is subsequently shaped in the mold cavity 88.
The synthetic support structure may be formed as a unitary member
or formed by one or more intertwined strands.
[0156] One or more expandable members 122, 134 and/or 136 may be
utilized to align an implant 104 and tissue 96 in a patient's body.
For example, one or more balloons may be utilized to align portions
106 and 108 of a blood vessel with a segment 104 which is to be
implanted into the blood vessel.
[0157] It should be understood that the present invention has a
plurality of different features which may be utilized separately or
in various combinations. It is also contemplated that the various
features of the invention may be utilized with known features from
the prior art. Although specific combination of features have been
described herein, it is contemplated that other combinations of
features will be apparent to those skilled in the art and will be
formed.
[0158] Furthermore, although certain applications are described
herein, those of ordinary skill in the art will appreciate other
applications for the present invention. For example, the scaffold
can be introduced with a non-surgical procedure by a radiologist or
other practitioner rather than a formal surgical procedure. The
procedure could utilize MRI guidance (open, standing vertical,
etc.), ultrasonic guidance, computer navigation, radiographic
guidance, PET scanning. The MRI may be a kinematic MRI to isolate
the organ or MRI with external pressure allowing one to visualize
the organ or tissue type specifically and then implant the scaffold
under a pressurized approach so that the external pressure applied
would hold the organ in the position while the scaffold would be
stabilized.
[0159] In view of the foregoing, it should be understood that
variations and modifications within the spirit and scope of the
invention might occur to those skilled in the art to which the
invention pertains. Accordingly, all expedient modifications
readily attainable by one versed in the art from the disclosure set
forth herein that are within the scope and spirit of the present
invention are to be included as further embodiments of the present
invention. The scope of the present invention is accordingly
defined as set forth in the appended claims.
* * * * *