U.S. patent application number 17/354708 was filed with the patent office on 2022-01-13 for flexible hollow lumen composite.
The applicant listed for this patent is THE SECANT GROUP, LLC. Invention is credited to Peter D. GABRIELE, Jeremy J. HARRIS, Steven LU, Andrew METZGER, Seth A. WINNER.
Application Number | 20220008190 17/354708 |
Document ID | / |
Family ID | |
Filed Date | 2022-01-13 |
United States Patent
Application |
20220008190 |
Kind Code |
A1 |
LU; Steven ; et al. |
January 13, 2022 |
FLEXIBLE HOLLOW LUMEN COMPOSITE
Abstract
A composite lumen includes a braided structure infused with an
impermeable elastic sealer. The braided structure has an inner
diameter of 3 mm or less and a braid angle greater than
100.degree.. The braided structure also has a wall thickness to
inner diameter ratio greater than 0.02, picks per inch from between
about 25 and about 135, and a number of ends between about 12 and
about 48, with a braid pattern that is selected from 1.times.1,
2.times.2, or 2.times.1 and with an effective yarn denier (yarn
denier.times.ply number) greater than 45.
Inventors: |
LU; Steven; (Somerville,
MA) ; GABRIELE; Peter D.; (Frisco, TX) ;
HARRIS; Jeremy J.; (Doylestown, PA) ; WINNER; Seth
A.; (Durham, NC) ; METZGER; Andrew; (Lafayette
Hill, PA) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
THE SECANT GROUP, LLC |
Telford |
PA |
US |
|
|
Appl. No.: |
17/354708 |
Filed: |
June 22, 2021 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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16153219 |
Oct 5, 2018 |
11065099 |
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17354708 |
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62569086 |
Oct 6, 2017 |
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International
Class: |
A61F 2/07 20060101
A61F002/07; A61L 27/50 20060101 A61L027/50; A61L 27/58 20060101
A61L027/58; A61L 31/14 20060101 A61L031/14; A61L 27/48 20060101
A61L027/48; A61L 31/12 20060101 A61L031/12; A61L 31/06 20060101
A61L031/06 |
Claims
1. A composite lumen comprising a braided structure infused with an
impermeable elastic sealer, the braided structure having an inner
diameter of 3 mm or less and having a braid angle greater than
100.degree., a wall thickness to inner diameter ratio greater than
0.02, picks per inch (PPI) from between about 25 and about 135,
number of ends between about 12 and about 48, with a braid pattern
that is selected from 1.times.1, 2.times.2, or 2.times.1 and with
an effective yarn denier (yarn denier.times.ply number) greater
than 45.
2. The composite lumen of claim 1 having a braid angle in the range
of 110.degree. to 135.degree., a wall thickness to inner diameter
ratio in the range of 0.03 to 0.07, PPI in the range of 50 to 120,
24 ends, a 1.times.1 braid pattern, and effective yarn denier in
the range of 180 to 360.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application is a division of U.S. patent application
Ser. No. 16/153,219 filed Oct. 5, 2018, which claims priority to
and the benefit of U.S. Provisional Application No. 62/569,086
filed Oct. 6, 2017, which is hereby incorporated by reference in
its entirety.
FIELD OF THE INVENTION
[0002] The present invention relates to the field of implantable
lumens, such as, for example, grafts to replace blood vessels. More
specifically, the present invention is related to flexible hollow
lumen composites.
BACKGROUND
[0003] Cardiovascular disease is the leading cause of death
worldwide. Although drug treatment of cardiovascular disease is
increasing, two of the primary methodologies currently used to
treat cardiovascular disease are coronary artery bypass grafts and
percutaneous coronary intervention, commonly referred to as
angioplasty.
[0004] During an angioplasty procedure, a stent is often implanted
into a restricted blood vessel to open the diameter of the blood
vessel. Various types of stents are currently known for such
procedures. Each type of stent has certain advantages, but each
type also suffers from one or more known complications or
weaknesses, which may include, but are not limited to, restenosis,
the need for long term use of anticoagulants, inhibition of natural
blood vessel motion (such as pulsatile motion), in-stent
thrombosis, improper healing, and potential for fracture of the
stent.
[0005] In contrast to percutaneous coronary intervention, a
coronary artery bypass graft is implanted to bypass a blockage or
obstruction in a coronary artery. Various types of grafts have been
used for bypass surgeries, including biological grafts (e.g.
autografts, allografts and xenografts) and artificial grafts (e.g.
polytetrafluoroethylene (PTFE), expanded PTFE (ePTFE), and
poly(ethylene terephthalate) (PET)). Additionally, although not
widely used, tissue-engineered grafts are being developed in which
the graft is produced in vitro.
[0006] Although each of the known grafts has certain advantages,
such as low cost, high availability, or similarity to native
tissue, each of the known grafts also suffers from one or more
known complications or weakness. For instance, while autografts are
the current gold standard because of their high durability, the
lack of availability and donor site morbidity continue to be
issues. Allografts typically take longer to integrate into the body
and require extensive processing before they are suitable for
implantation. Artificial grafts are readily available but may be
more prone to infection, thrombosis, or intimal hyperplasia and may
require long term use of medication, such as anticoagulants.
Although tissue-engineered grafts overcome many of the problems
associated with commonly-used biological and artificial grafts,
tissue-engineered grafts are extremely expensive and take a long
time to manufacture.
[0007] In general, native vessels remain the preferred choice for
revascularization procedures, however, such tissues are not always
available. In such cases, synthetic materials, such as expanded
polytetrafluoroethylene (ePTFE) and poly(ethylene terephthalate)
(PET), have been used successfully as vascular conduits when the
graft diameter exceeds 6 mm. Results have been poor, however, with
grafts less than 6 mm in diameter, due to the development of
thrombi and intimal hyperplasia.
[0008] The use of textile technology to make three-dimensional
hollow lumen structures is a well-known art. While flexible,
water-impermeable lumens are described in U.S. Pat. App. Pub. No.
2015/0320542 (incorporated herein by reference) and work well,
continued improvements are still desirable to further enhance the
performance of such devices.
BRIEF DESCRIPTION OF THE INVENTION
[0009] In some embodiments, a composite lumen includes an extruded
tube of a composite including a poly(glycerol sebacate) (PGS)
matrix mixed with a PGS thermoset filler. The composite lumen also
includes an overbraid structure overlying an outer surface of the
extruded tube.
[0010] In some embodiments, a method of forming a composite lumen
includes extruding a poly(glycerol sebacate) (PGS) tube of a
composite including a PGS matrix mixed with a PGS thermoset filler.
The method also includes applying an overbraid structure over an
outer surface of the extruded tube.
[0011] Exemplary embodiments are directed to flexible composite
braids, composite braids formed from such processes, the
composition of a textile and elastic sealer which includes the
composite braid, and the use of these composite braids for the
repair and regeneration of tubular tissues for grafts and other
applications to replace diseased or damaged tissue vessels.
[0012] Exemplary embodiments provide a degradable endogenous graft
(DEG) including a luminal composite of a textile engineered braided
structure, embedded or encapsulated with an elastic biodegradable
polymer infusion coating comprising poly(glycerol-sebacate) (PGS)
that enhances biomimetic elastomeric properties, provides
mechanobiological tissue compliance, and that remains flexible and
blood/water-impermeable to allow cardiovascular tissue to replace
said composite in vivo.
[0013] A specified range and combination of different braiding
parameters and sealing parameters may be tuned to fit a variety of
reparative and regenerative applications for luminal tissues
depending upon a particular application.
[0014] A patient with chronic cardiovascular disease may eventually
run out of autograft transplant options or may not be of such
required health to survive the trauma of harvesting autologous
vascular tissues. Having an option to use a DEG prosthesis that
offers the patient immediate selection and quality of care in an
emergency is both life-saving and economical.
[0015] Exemplary embodiments provide a luminal composite that acts
as an in vivo resorbable scaffold structure that replaces diseased
or degenerated vascular structures via endogenous regeneration of
the luminal vascular anatomy. Such a composite provides a vascular
structure that can be stored without extensive biologic storage
logistics or conditions and provides the surgeon with an
off-the-shelf patient-ready regenerative prosthesis.
[0016] Furthermore, exemplary embodiments do not require
preconditioning or incorporation of active pharmaceuticals or
biologic growth or trophic factors to establish tissue residence
and differentiation into the final tissue anatomy and
physiology.
[0017] Various features and advantages of the present invention
will be apparent from the following more detailed description,
taken in conjunction with the accompanying drawings which
illustrate, by way of example, the principles of the invention.
BRIEF DESCRIPTION OF THE DRAWINGS
[0018] FIG. 1 shows a braid structure of a lumen in accordance with
an exemplary embodiment coated with an elastic sealer.
[0019] FIG. 2 shows a cross-section of a braid structure of a lumen
in accordance with an exemplary embodiment infused with an elastic
sealer.
[0020] FIG. 3 shows the improvement in a PGS infusion coating of a
braid with a prewet-and-sonicate preconditioning step.
[0021] FIG. 4A shows a side view of a lumen formed by a continuous
crochet action around a mandrel in an exemplary embodiment.
[0022] FIG. 4B shows an end view of the lumen of FIG. 4A.
[0023] FIG. 4C shows a second side view of the lumen of FIG.
4A.
[0024] FIG. 5 shows the loop structure of a warp knitted structure
in an exemplary embodiment.
[0025] FIG. 6 shows a schematic profile of a double needle bar warp
knitting machine in an exemplary embodiment.
[0026] FIG. 7A shows a side view of an extruded PGS tube with a
polyglycolide (PGA) overbraid in an exemplary embodiment.
[0027] FIG. 7B shows an end view of the extruded PGS tube with the
PGA overbraid of FIG. 7A.
[0028] Wherever possible, the same reference numbers will be used
throughout the drawings to represent the same parts.
DETAILED DESCRIPTION OF THE INVENTION
[0029] A major advantage of a braid-based technology over knitting
or weaving is in the engineering properties associated with the
braided construct. The braided construct may bio-mimic
mechanobiological features such as fore-shortening and elongation,
radial distension to provide pulsatile mechanics in a hemodynamic
environment, kink-resistant vascular characteristics, and an
anatomically-correct long-axis profile similar to actual arterial
and venous anatomy (arterial vascular structures naturally diminish
bore-diameter as a function of distance from the heart for arteries
whereas venous vascular structures naturally expand their bore
diameter from the most distal vascular/capillary location returning
to the heart). In some embodiments, a braid mandrel is configured
to simulate the natural diminishing bore diameter during
manufacture, providing a more realistic hemodynamic structure in
the finished braided lumen.
[0030] The structure of woven tubes may have very low water
permeability but lends them little flexibility and kink resistance
without corrugation processing. Knitted tubes have very high
flexibility but may be structurally weak and have high water
permeability. Luminal structures that are braided offer high
flexibility and kink resistance and may maintain their circular
morphology through compression and tension, both axially and
radially. Although textile braids may be manufactured with low
water permeability, it comes at a cost to their flexibility.
[0031] Exemplary embodiments provide highly flexible braids that
are infusion coated with an elastic sealer to make kink-resistant,
water-impermeable composite braids as illustrated in FIG. 1 and
FIG. 2. The interlacing pattern of the braids is visible in FIG. 1.
The penetration of the coating between the braids is visible in
FIG. 2.
[0032] Variations in yarn thickness, yarn density, yarn tension,
porosities, braid angle, and braiding patterns are employed to form
a braided structure suitable for exemplary embodiments that, when
combined with infusion of an elastic material, seals the
interstitial spaces between fibers with varying amounts of elastic
material that create a water-impermeable wall. Thus, infusing
creates an embedded coating that encapsulates the fibrils. Specific
combinations of braiding and infusion-coating parameters may yield
a variety of composite braids with different levels of flexibility
and water permeability.
[0033] The uniformity of the PGS (as used herein, PGS includes both
neat PGS and PGS copolymers, such as, for example, PGS-urethane
(PGSU)) infusion coating provides many engineering features to the
`naked` braid that otherwise would not be expected. The infusion of
the elastomeric PGS polymer into the braid-lattice embeds the
individual fibers of the yarn, providing a cohesive and uniform
strength, matrix energy transfer and dissipation, and memory for
recovery during radial distention. This action resulting from the
embedding minimizes fiber-to-fiber friction and maximizes kinetic
energy dissipation important in a continuously-active in vivo
structure.
[0034] Exemplary embodiments achieve a uniform infusion that
provides a level of strength to elongation that would otherwise
fail to yield to above-normal physical tension or internal
hemodynamic pressure. Uniform PGS infusion also provides
`trimability` to eliminate fiber fraying.
[0035] The ability to create composite braids with different
characteristics allows the building of constructs that can match
the physical properties of luminal tissues that the composite braid
is intended to repair and/or regenerate.
[0036] A presently-preferred embodiment employs a maypole braid
made from polyglycolide (PGA) yarn and subsequently infusion coated
in poly(glycerol sebacate) (PGS). One advantage of using PGS as an
elastic infusible sealer/coating is its anti-microbial,
non-inflammatory, non-immunogenic, and non-thrombogenic properties.
By using PGS as a degradable elastic infusion sealer-coating, the
acute physiological response towards the composite braid may be
modulated to influence a post-implantation mechanobiological
healing response. Although discussed primarily with respect to PGA
braids and PGS infusion coatings, other biodegradable yarns (e.g.,
polylactide (PLA), poly(lactic-co-glycolic acid) (PLGA),
polycaprolactone (PCL), polydioxanone (PDO), poly(trimethylene
carbonate) (PTC), or PGSU) may be used, as may other biodegradable
elastomers (e.g., polyurethane (PU) or PGSU) be used for the
infusion coating.
[0037] Particular combinations of braiding and infusion coating
parameters allow for a flexible (i.e., small kink radius) and
water-impermeable anatomically-similar luminal construct.
[0038] To create flexible and water-impermeable braids of different
diameters, both braiding and infusion coating parameters need to be
adjusted to tune wall thickness, braid density, and % PGS mass.
Wall thickness is influenced by yarn denier, ply, picks per inch
(PPI), and ply twist. Braid density is influenced by yarn denier,
PPI, ply, and number of ends. % PGS mass is influenced by the
infusion coating method, infusion coating solution concentration,
braid density, and wall thickness.
[0039] Braid stiffness or suppleness may also be influenced by
thermal annealing to modulate crystallinity. Crystallinity imparted
by thermal annealing may be affected by braiding and yarn tension,
as well as by the degradation profile.
[0040] Degradation of the composite lumen formed by the resorbable
textile and resorbable elastic infused sealer may be tuned by the
amount of textile, filament size, and included elastomer (e.g.,
braid density, denier/filament, or % PGS mass). Thermal annealing
to impart crystallinity into the textile structure may also be
modified to tune the degradation rate of the textile braid. By
having the ability to modify the degradation rate of the composite
braid, the composite braid may be tuned to match the formation of
neotissue in regenerative applications. By matching the degradation
and healing rates, issues such as loss of mechanical integrity
and/or stress-shielding may be prevented.
[0041] Exemplary embodiments are particularly useful for
construction of small-bore lumens to replace vessels having an
inner diameter of 6 mm or less, such as those as small as 3 mm. In
some embodiments, the construction of a small bore vessel having an
inner diameter of 3 mm is formed by providing a braid with a braid
angle greater than 100.degree., a wall thickness to inner diameter
ratio greater than 0.02, picks per inch (PPI) from between about 25
and about 135, number of ends between about 12 and about 48, with a
braid pattern that is selected from 1.times.1, 2.times.2, or
2.times.1 and with an effective yarn denier (defined as yarn
denier.times.ply number) greater than 45.
[0042] A presently-preferred embodiment has a braid angle in the
range of 110 to 135, such as 120 to 130, a wall thickness to inner
diameter ratio is in the range of 0.03 to 0.07, such as 0.05 to
0.07, PPI in the range of 50 to 120, such as 50 to 80, 24 ends, a
1.times.1 braid pattern, and effective yarn denier in the range of
180 to 360.
[0043] The infusion coating with the elastic material may be
accomplished by dip coating, spray coating, and/or primed by
wetting the yarn with the solvent prior to coating. Infusion may be
optimized using high-pressure coating or injection technology such
as that used to make reinforced high-performance hoses for harsh
environments.
[0044] The infusion coating may vary by solids or viscosity and may
be augmented with additives to enhance yarn fibril wetting for
encapsulation and embedding.
[0045] The use of infusion technology achieves a uniformity in the
PGS infusion coating and unexpectedly achieves better results that
otherwise would not be expected. The infusion of the elastomeric
PGS polymer into the braid-lattice embeds the individual fibers of
the yarn, thereby providing a cohesive and uniform strength, matrix
energy transfer and dissipation, and memory for recovery during
radial distention.
[0046] This action resulting from the embedding minimizes
fiber-to-fiber friction and maximizes kinetic energy dissipation,
which is important in a continuously active in vivo structure.
Uniform infusion provides a level of strength-to-elongation that
would otherwise fail to yield to above-normal physical tension or
internal hemodynamic pressure.
[0047] The infusion coating is generally greater than 10% by weight
of the lumen and is cross-linked after coating to achieve a cross
link density near thermoset. In some presently-preferred
embodiments, the lumen is in the range of 15% to 35% by weight of
the infused PGS elastic material, such as about 20% to about 30% by
weight.
[0048] In some embodiments, the infusion coating may not readily
penetrate the braid as a result of physical or chemical resistance
to the wetting of the fibers by the infusion coating or the fiber
bundles of the braid may be too tight for the infusion coating
polymer to fully wet the bundle. As a preliminary step to the
infusion coating process, the braids may be preconditioned in a
surface-active treatment (e.g., a dip, bath, or ultrasonic infusion
of a wetting agent solution or a simple solvent solution, etc.) to
modify the fiber resin surface interaction and promote resin
penetration via wetting agent or etching of and into the
interstitial lattice network to pre-wet or surface modify the fiber
and provide better infusion and surface contact of the polymer with
the braid fibers.
[0049] FIG. 3 shows that a pre-wetting and sonication
preconditioning step prior to dip coating significantly reduces the
water permeability of the resulting PGS infusion coated braid. A
dip coating without a previous pre-wet and sonicate step produced a
coated braid having a water permeability in the range of about 60
to about 100 mL/cm.sup.2/min). In contrast, by pre-wetting and
sonicating prior to dip coating, the process gives a coated braid
having a water permeability of only about 5 mL/cm.sup.2/min or
less.
[0050] Such preliminary treatments may eliminate "dry" or "hot"
spots within the braid lattice, that is eliminate spaces within the
bulk structure that have been excluded from the infusion process.
This pre-treatment helps protect against premature failure from an
aneurysm or blow-out from hemostatic pressure. Furthermore, the
fibers themselves can be pretreated prior to braiding. If the
braided construct is scrubbed prior to manipulation, a wetting
treatment may be incorporated into the scrubbing solution.
[0051] Preliminary treatments may include the use of wetting agents
incorporated into the biodegradable polymer composition used to
form the fiber of the braid and/or sheath/core technology to
produce a selective wetting modification of the surface of the
fibers during manufacture prior to braiding.
[0052] It will further be appreciated that braids may be plasma
treated prior to infusion and that the braids may be exposed to
ethylene oxide sterilization gas prior to coating to modify the
surface to change the wetting action.
[0053] Other coating techniques for application of the infusion
coating and/or any pretreatment coating include vapor deposition
and infusion, as well as ultrasonic bathing of the braided
structure in a wetting or polymer bath prior to the PGS infusion
coating.
[0054] Braided structures in accordance with certain embodiments
described herein have been successfully implanted into rats and
pigs and remodeled into native vascular tissue, and composite
braids made with these parameters may be watertight with a water
permeability of 0 mL/cm.sup.2/min and a kink radius of less than 10
mm.
[0055] According to another exemplary embodiment, the lumen
structure is a crocheted lumen structure. Among the advantages of a
crocheted lumen is the ability to form the lumen structure from a
single yarn, including the possibility of the yarn as a single
monofilament. Accordingly, there is a continuous thread throughout
the article and even if one loop breaks, the structure remains
stable. Crocheted lumens elongate and foreshorten, radially
distend, and may be coated in the same manner as the braid, both
with respect to the elastomeric infusion coating and with respect
to any pretreatments. Depending on the loop density, crocheted
lumens may more readily accept an infused coating without
pretreatment while still maintaining the uniformity of the inner
and outer lumen walls.
[0056] FIG. 4A, FIG. 4B, and FIG. 4C illustrate a lumen formed by a
continuous crochet action around a mandrel. FIG. 4A shows the
crochet pattern on the lumen. FIG. 4B shows the cylindrical opening
of the lumen. FIG. 4C shows the two opposite ends of the single
strand of yarn used to form the lumen extending from opposite ends
of the lumen.
[0057] In some embodiments, a circular warp knit or a tubular
double needle bar warp construction may be employed. Because they
are both warp knit constructions (not weft knit), they have good
stability and will not unravel when cut. Additionally, the density
and stretch properties are tunable by modifying pattern, yarn size,
or course counts.
[0058] Warp knitted structures are created using a continuous
interlocking chain of loops, resulting in stable structures.
Multiple fibers are combined together by the interlocking of loops
along the length of the fabric being produced. The locking of these
loops creates structure with both a high level of compliance and
strength, as well as limiting material fraying and fabric runs. A
warp knitted structure has an increased suture retention over a
braided construction as a result of its inter-looping structure, as
shown in FIG. 5.
[0059] In some embodiments, a double needle bar warp knitting
machine 60, as shown schematically in FIG. 6, is utilized to create
a hollow lumen structure with tunable properties, including, but
not limited to, porosity, density, thickness, radial distension,
and longitudinal stretch. The double needle bar warp knitting
machine 60 includes a first guide bar 61, a second guide bar 62, a
third guide bar 63, a fourth guide bar 64, a fifth guide bar 65, a
sixth guide bar 66, a front needle 68, and a back needle 70 forming
a front layer 72, a middle layer 74, and a back layer 76 of the
fabric.
[0060] A double needle bar warp knitting machine has two needle
beds, allowing it to create two independent fabric layers at one
time as well as combine those two layers in specific areas. The
double needle bar machine creates fabric layers that are then knit
together on edges along the length, creating a continuous, in-line
seam up the fabric and resulting in a hollow lumen structure.
Double needle bar warp knitting machines have a large amount design
flexibility, and features such as porosity, density, compliance,
and stretch may be modified by changing knit pattern, machine
gauge, and course counts within the knit fabric.
[0061] In some embodiments, a circular warp knitter is used to form
a knitted fabric by interlocking loops of fibers together, giving
it compliance, strength, and dimensional stability. A circular warp
knitter operates similarly to a normal warp knitting machine but is
limited by the pattern and density that are able to be created.
However, an advantage of a circular warp knitter is the creation of
a seamless tube, as the needles on the machine are arranged
continuously around an actuating cylinder, as opposed to the double
needle bar, which has two needle beds parallel to one another.
Circular warp knitting design is a product of the size of the knit
cylinder and the density of needles on the cylinder, resulting in
new cylinders being needed based on density and diameter of the
final knit construction.
[0062] According to another exemplary embodiment, a hollow lumen is
prepared as an extruded composite tube. The tube is extruded from a
composite composition including a PGS resin and small particles
(e.g., particle sizes of less than 1000 microns) of a PGS thermoset
filler material. The composite may be as described in U.S. Pat.
App. Pub. No. 2017/0246316, incorporated herein by reference.
[0063] The matrix resin of the extruded tube is preferably selected
to be able to flow or soften at a given temperature to allow for
particle integration. Particularly in the case where the resin is
PGS, the PGS resin preferably has a weight average molecular weight
in the range of 5,000 to 50,000 Da. In some embodiments, the PGS
resin has a weight average molecular weight in the range of 15,000
to 25,000 Da.
[0064] The matrix may be composed entirely of the polymer resin or
may include one or more additional components. In some embodiments,
the matrix contains one or more drugs, medicaments, or other
biologically- and/or pharmaceutically-active ingredients, which may
be incorporated therein for controlled release during subsequent
resorption or degradation of the matrix due to the surface-eroding
characteristics of PGS.
[0065] The thermoset PGS filler of the composite extruded tube has
been processed into a flour or powder of fine particle size (e.g.,
less than 1000 microns). The PGS thermoset filler cross-link
density is about 0.07 mol/L or greater, which is calculated with
respect to the thermoset material prior to particularization by
soaking samples in tetrahydrofuran for 24 hours to obtain a swollen
mass, and then drying until a constant dry mass is acquired
(typically about 3 days) and the swelling percentage is then used
to calculate the crosslink density using the Flory-Rehner
expression for tetra-functional affine networks. Filler particle
size may vary, but in some embodiments the average particle size is
in the range of about 75 to about 300 microns, such as, for
example, about 175 to about 250 microns.
[0066] The molar ratio of glycerol:sebacic acid in the thermoset
PGS used for the filler material may vary but typically is in the
range of 0.7:1 to 1.3:1, with a preference in some embodiments for
a 1:1 molar ratio. While the stoichiometric ratios of glycerol to
sebacic acid may be varied for the PGS particles, the particles
should still be of a surface energy similar to that of the resin
matrix. For example, a composite that includes a PGS thermoset
filler made from 1:1 glycerol:sebacic acid molar ratio may be
dispersed in a PGS resin matrix that also has a 1:1
glycerol:sebacic acid molar ratio.
[0067] The weight percentage of filler in the composite ranges from
about 10% by weight to about 90% by weight filler, typically about
40% by weight to about 70% by weight filler, and the resulting
composite is then extruded to form a tube using a Brabender or
fiber extrusion or other suitable extrusion device to form tubes
having any suitable outer diameter. Exemplary embodiments have
shown to be particularly useful with small outer diameters, such as
those having an outer diameter of about 6 mm or less, such as
between 2 and 4 mm, such as about 2.5 mm or about 3.0 mm.
[0068] While the lumen may be useful in its initially-extruded
form, in some embodiments an overbraid is applied following
extrusion in which fibers of a bioresorbable material (PGA, PLA,
PLGA, PGS, etc.) are braided overlying the exterior surface of the
tube. The addition of the braid may aid in providing increased
burst strength, kink resistance, and stability to the extruded tube
and thus a superior result in the resulting lumen. Instead of an
overbraid, the overlying layer applied surrounding the extruded
tube may also be a crochet or knit textile.
[0069] The overbraid is a separate layer formed around the extruded
tube surface. In some embodiments, the overbraid is heat-set to
retain its shape even when the lumen is cut or manipulated. In
other embodiments, the lumen is dip coated to physically connect
the overbraid with the extruded tube. By dip coating, the overbraid
maintains its morphology without heat setting and is then secured
to the underlying extruded tube. In some embodiments, the lumen is
dip coated in PGS or other bioresorbable resin that infiltrates
some of the space within the braid, such that upon curing of the
dip coated resin, the overbraid is laminated to the underlying
tube. Additional advantages of applying PGS resin to the overbraid
include reducing potential for inflammation from the textile and
decreased adhesion formation.
[0070] FIG. 7A and FIG. 7B illustrate a lumen formed by extrusion
followed by application of an overbraid. FIG. 7A shows the
overbraid pattern with parts of the lumen visible through the
overbraid. FIG. 7B shows the cylindrical opening of the lumen and
the relative thicknesses of the lumen and the overbraid.
[0071] In order to impart structural support while maintaining
flexibility of the extruded tube, the overbraid braiding parameters
may differ from those described in earlier embodiments. For a
2.5-mm outer diameter extruded tube, the overbraid braiding
parameters may include an overbraid braid angle in the range of 75
to 151, such as 100 to 120, a PPI in the range of 30 to 150, such
as 40 to 80, 24 to 36 ends, a 1.times.1 braid pattern, or an
effective yarn denier in the range of 45 to 90.
[0072] The wall thickness of the extruded tube for a 2.5-mm outer
diameter may range from 200 .mu.m to 1200 .mu.m in thickness,
preferably from 200 .mu.m to 500 .mu.m thick. It will be
appreciated that as the extruded tube wall thickness decreases, the
overbraid braiding parameters may be adjusted to provide more
structural support while maintaining flexibility of the tube. It
will further be appreciated that wall thickness may change as outer
diameter increases beyond 2.5 mm, although in most embodiments the
thickness should not increase beyond the point at which the tube
loses flexibility.
[0073] These embodiments have been reduced to practice and were the
subject of small-diameter arterial tissue-engineered vascular graft
(TEVG) in a rat model of infrarenal abdominal aorta interposition
grafting. Extruded grafts were fabricated of PGS with some
embodiments having a PGA braid over the extruded lumen. A total of
30 cases were implanted, with 5 cases in each group evaluated at
one month and 10 cases in each group evaluated at three months.
[0074] At one month, remodeled grafts displayed an endothelial cell
monolayer, contractile vascular smooth muscle cells, extracellular
matrix (ECM) deposition, and macrophage infiltration, without any
incidence of graft dilatation or rupture. The inner diameter, wall
thickness, elastin thickness, ECM area, and total number of
macrophages (based on CD68+) in the remodeled grafts were measured,
and there was no significant difference between the two groups
except for in wall thickness of the remodeled graft. These results
reflect that exemplary embodiments using an extruded lumen lead to
the formation of well-organized vascular neotissue without aneurysm
or graft rupture at one-month follow-up.
[0075] At three months, the extracellular matrix (ECM) deposition
and the inner diameter and wall thickness of the braid grafts were
comparable to that of native aorta. Both graft types demonstrated
10% calcified area at 3 months due to the remaining scaffold. The
data suggests that the PGS-extruded grafts degrade rapidly to lead
to rich cellular infiltration, but mechanical support such as
implementation of PGA braided technology may be needed to induce
ECM formation and prevent graft dilatation over time.
[0076] In another embodiment, the exterior and/or the interior of
the extruded lumen embodiments may be coated following extrusion,
such as by dip coating, or, in some embodiments, may be co-extruded
with an outer shell of another material. In some embodiments, only
the exterior surface is coated to permit intimate contact of the
inner lumen surface with cells with the PGS material and thus
encourage regeneration of native tissue to begin at the inner wall
of the conduit.
[0077] The coating may be applied over the extruded lumen, over the
over-braided structure applied to the extruded lumen, or both, with
the lumen being plugged prior to application of the coating if a
coating on the interior surface is to be avoided. In some
embodiments, the coating is a urethane coating that may be
achieved, for example, by dipping, spraying or otherwise applying
an isocyanate. The isocyanate may be an aliphatic isocyanate, such
as, for example, hexamethylene diisocyanate (HDI), but in some
embodiments may instead be an aromatic isocyanate, such as toluene
diisocyanate (TDI) or methylene diphenyl isocyanate (MDI), again by
way of example. The use of a urethane or other outer coating may
further enhance burst strength and/or suturability.
[0078] While described primarily herein with respect to lumens
constructed to achieve properties suitable for use as a vascular
graft, the invention is not so limited and other graft
constructions may also be created, as well as any other tissue
vessel that is necessary to be resected and replaced and which in
turn supports endogenous regeneration of native tissue.
[0079] For vascular grafts, exemplary embodiments may be employed
for use as coronary artery bypass grafts, arteriovenous grafts,
cerebral artery bypass grafts, pediatric shunts such as
Blalock-Taussig (BT) shunts and sano shunts, peripheral grafts such
as femoral-popliteal bypass, femoral-femoral bypass,
aortic-bifemoral bypass, axillary-bifemoral bypass, femoral-tibial
bypass, and dorsalis-pedis bypass.
[0080] Diseases/conditions where lumens in accordance with
exemplary embodiments may be employed may include, but are not
limited to, any of coronary artery disease, cardiac aneurysm,
hypertension, cardiac stroke, vascular aneurysm, kidney failure,
vascular occlusion, diabetes, and organ transplantation.
[0081] In addition to grafts, other tubular tissues for which
lumens in accordance with exemplary embodiments may be employed
include, for example, nerve guide and conduit tissues, lymphatic
vessels, gastrointestinal tract tissues, and urogenital tract
tissues, including the ureter, vas deferens, and fallopian
tubes.
[0082] It should be understood that while the invention has been
described with reference to one or more embodiments, various
changes may be made, and equivalents may be substituted for
elements thereof without departing from the scope of the invention.
In addition, many modifications may be made to adapt a particular
situation or material to the teachings of the invention without
departing from the essential scope thereof. Therefore, it is
intended that the invention not be limited to the particular
embodiment disclosed as the best mode contemplated for carrying out
this invention. In addition, all numerical values identified shall
be interpreted as though the precise and approximate values are
both expressly identified.
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