U.S. patent application number 10/351881 was filed with the patent office on 2003-07-17 for bioabsorbable fibers and reinforced composites produced therefrom.
This patent application is currently assigned to BioAmide, Inc.. Invention is credited to Barrows, Thomas H..
Application Number | 20030134099 10/351881 |
Document ID | / |
Family ID | 22096353 |
Filed Date | 2003-07-17 |
United States Patent
Application |
20030134099 |
Kind Code |
A1 |
Barrows, Thomas H. |
July 17, 2003 |
Bioabsorbable fibers and reinforced composites produced
therefrom
Abstract
This invention relates to bioabsorbable fibers, comprising a
semicrystalline fiber-forming core polymer and a amorphous sheath
polymer, wherein the core polymer and sheath polymer are separately
melt extruded and connected to one another through an adhesive
bond. The present invention also relates to reinforced composites
of the bioabsorbable fibers, and to devices comprising the
reinforced composites. The devices are suitable for in vivo
implantation. Some embodiments of the present devices can also
support high loads, making them useful for fracture fixation and
spinal fusion. The invention also relates to methods of making the
various materials of the invention.
Inventors: |
Barrows, Thomas H.;
(Austell, GA) |
Correspondence
Address: |
MICHAEL BEST & FRIEDRICH, LLP
ONE SOUTH PINCKNEY STREET
P O BOX 1806
MADISON
WI
53701
|
Assignee: |
BioAmide, Inc.
|
Family ID: |
22096353 |
Appl. No.: |
10/351881 |
Filed: |
January 27, 2003 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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10351881 |
Jan 27, 2003 |
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09582833 |
Jun 30, 2000 |
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6511748 |
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09582833 |
Jun 30, 2000 |
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PCT/US99/00252 |
Jan 6, 1999 |
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60070610 |
Jan 6, 1998 |
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Current U.S.
Class: |
428/297.4 ;
428/373 |
Current CPC
Class: |
A61F 2002/30062
20130101; Y10T 428/24994 20150401; A61L 31/12 20130101; A61L 27/48
20130101; D01F 6/00 20130101; D01F 8/14 20130101; A61B 17/72
20130101; A61L 31/128 20130101; A61B 2017/00004 20130101; Y10T
428/2929 20150115; A61L 27/48 20130101; C08L 67/04 20130101; A61F
2210/0004 20130101; Y10T 428/2907 20150115; A61F 2/82 20130101;
A61L 31/06 20130101; Y10T 428/2933 20150115; A61L 31/128 20130101;
Y10T 428/2931 20150115; Y10T 428/249924 20150401; C08L 67/04
20130101; C08L 67/04 20130101; C08L 67/04 20130101; A61L 31/148
20130101; A61F 2/30965 20130101; A61L 31/06 20130101; A61F 2/4455
20130101 |
Class at
Publication: |
428/297.4 ;
428/373 |
International
Class: |
B32B 027/04; D02G
003/00 |
Claims
What is claimed is:
1. A bioabsorbable fiber comprising a core of a semicrystalline
fiber-forming bioabsorbable core polymer with a crystalline core
melting temperature, and a sheath of an amorphous bioabsorbable
sheath polymer with a softening point below the crystalline core
melting temperature, wherein the core polymer and sheath polymer
are separately melt extruded, and the sheath is connected to the
core through an adhesive bond.
2. The bioabsorbable fiber of claim 1, wherein the core polymer is
selected from the group consisting of poly(L-lactide),
polyglycolide, poly(epsilon-caprolactone), polydioxanone,
poly(ester-amide)s, any combination thereof, and any copolymers
thereof wherein trimethylene carbonate is a comonomer.
3. The bioabsorbable fiber of claim 1, wherein the sheath polymer
comprises at least one polymer selected from the group consisting
of poly(ester-amide)s, tyrosine-derived polycarbonates,
poly(trimethylene carbonate), poly(dl-lactide), polydioxanone, and
any copolymer, mixture, or blend thereof.
4. The bioabsorbable fiber of claim 1, wherein the sheath polymer
comprises a copolymer which is the product of copolymerization of
at least two monomers selected from the group of monomers
consisting of epsilon-caprolactone, trimethylene carbonate,
L-lactide, dl-lactide, glycolide, and para-dioxanone.
5. The bioabsorbable fiber of claim 1 wherein the core polymer is
poly(L-lactide) and the sheath polymer is a block copolymer of
poly(ester-amide) and L-lactide.
6. The bioabsorbable fiber of claim 5, wherein the sheath polymer
is a block copolymer of L-lactide and 1,6-hexanediol terminated
poly[2,5-dioxahexane-1,6-di(carbonyloxy)hexane-1,6-di(amidocarbonylpentam-
ethylene)].
7. The bioabsorbable fiber of claim 1, wherein the sheath is bound
to the core with sufficient strength that the sheath elongates with
the core and does not separate therefrom through hot stretching,
elongation, and cooling of the fiber.
8. A reinforced composite, comprising: a plurality of filaments of
a bioabsorbable fiber, the bioabsorbable fiber comprising a core of
a semicrystalline fiber-forming bioabsorbable core polymer with a
crystalline core melting temperature, and a sheath of an amorphous
bioabsorbable sheath polymer with a softening point below the
crystalline core melting temperature, wherein the core polymer and
sheath polymer are separately melt extruded, and the sheath is
connected to the core through an adhesive bond; and a molding resin
reinforced with the plurality of fibers.
9. The reinforced composite of claim 8, wherein the core polymer is
selected from the group consisting of poly(L-lactide),
polyglycolide, poly(epsilon-caprolactone), polydioxanone,
poly(ester-amide)s, any combination thereof, and any copolymers
thereof wherein trimethylene carbonate is a comonomer.
10. The reinforced composite of claim 8, wherein the sheath polymer
comprises at least one polymer selected from the group consisting
of poly(ester-amide)s, tyrosine-derived polycarbonates,
poly(trimethylene carbonate), poly(dl-lactide), polydioxanone, and
any copolymer, mixture, or blend thereof.
11. The reinforced composite of claim 8, wherein the sheath polymer
comprises a copolymer which is the product of copolymerization of
at least two monomers selected from the group of monomers
consisting of epsilon-caprolactone, trimethylene carbonate,
L-lactide, dl-lactide, glycolide, and para-dioxanone.
12. The reinforced composite of claim 8, wherein the molding resin
consists of the same polymer as the sheath polymer.
13. The reinforced composite of claim 9, wherein the molding resin
is filled with at least 10% and up to 70% of the bioabsorbable
fibers by volume.
14. The reinforced composite of claim 9, wherein the molding resin
is filled with a reinforcement filler selected from the group
consisting of the bioabsorbable fibers, a mineral filler, and a
combination of the bioabsorbable fibers and the mineral filler.
15. The reinforced composite of claim 14, wherein the mineral
filler comprises hydroxyapatite.
16. The reinforced composite of claim 15 wherein the injection
molding resin is filled with 10-70% by volume of hydroxyapatite
particles that have been treated with a silane coupling agent.
17. The reinforced composite of claim 16 in which the silane
coupling agent is trimethoxyaminopropyl silane.
18. A device designed for in vivo implantation, fabricated from a
reinforced bioabsorbable composite, the reinforced composite
comprising: a plurality of filaments of a bioabsorbable fiber, the
bioabsorbable fiber comprising a core of a semicrystalline
fiber-forming bioabsorbable core polymer with a crystalline core
melting temperature, and a sheath of an amorphous bioabsorbable
sheath polymer with a softening point below the crystalline core
melting temperature, wherein the core polymer and sheath polymer
are separately melt extruded, and the sheath is connected to the
core through an adhesive bond; and a molding resin reinforced with
the plurality of fibers.
19. The device of claim 18, wherein the core polymer is selected
from the group consisting of poly(L-lactide), polyglycolide,
poly(epsilon-caprolactone), polydioxanone, poly(ester-amide)s, any
combination thereof, and any copolymers thereof wherein
trimethylene carbonate is a comonomer.
20. The device of claim 18, wherein the sheath polymer comprises at
least one polymer selected from the group consisting of
poly(ester-amide)s, tyrosine-derived polycarbonates,
poly(trimethylene carbonate), poly(dl-lactide), polydioxanone, and
any copolymer, mixture, or blend thereof.
21. The device of claim 18, wherein the sheath polymer comprises a
copolymer which is the product of copolymerization of at least two
monomers selected from the group of monomers consisting of
epsilon-caprolactone, trimethylene carbonate, L-lactide,
dl-lactide, glycolide, and para-dioxanone.
22. The device of claim 18, wherein the reinforced composite is in
a configuration suitable for use as a spinal fusion cage
implant.
23. The device of claim 18, wherein the reinforced composite is in
a configuration suitable for use as an intramedullary rod.
24. The device of claim 18, wherein the reinforced composite is in
a configuration suitable for use as a stent.
25. A method of making a bioabsorbable fiber, comprising the steps
of: a. selecting a core polymer which is semicrystalline,
fiber-forming, and bioabsorbable, with a crystalline core melting
temperature; b. selecting a sheath polymer which is bioabsorbable,
and which forms an amorphous phase on polymerization, with a
softening point below the crystalline core melting temperature; c.
separately melt extruding the core polymer and sheath polymer; and
d. forming an adhesive bond between the core polymer and sheath
polymer, such that the resulting bioabsorbable fiber comprises a
core of the core polymer and a sheath of the sheath polymer.
26. The method of making the bioabsorbable fiber of claim 25,
wherein the core polymer is selected from the group consisting of
poly(L-lactide), polyglycolide, poly(epsilon-caprolactone),
polydioxanone, poly(ester-amide)s, any combination thereof, and any
copolymers thereof wherein trimethylene carbonate is a
comonomer.
27. The method of making the bioabsorbable fiber of claim 25,
wherein the sheath polymer comprises at least one polymer selected
from the group consisting of poly(ester-amide)s, tyrosine-derived
polycarbonates, poly(trimethylene carbonate), poly(dl-lactide),
polydioxanone, and any copolymer, mixture, or blend thereof.
28. The bioabsorbable fiber of claim 26, wherein the sheath polymer
comprises a copolymer which is the product of copolymerization of
at least two monomers selected from the group of monomers
consisting of epsilon-caprolactone, trimethylene carbonate,
L-lactide, dl-lactide, glycolide, and para-dioxanone.
29. The method of making the bioabsorbable fiber of claim 26,
wherein the adhesive bond between the core and sheath is formed by
forcing the separately melting the extruded core polymer and
extruded sheath polymer into a single die.
30. The method of making the bioabsorbable fiber of claim 26,
wherein adhesive bond between the sheath and the core is
sufficiently strong that the sheath elongates with the core and
does not separate therefrom through hot stretching, elongation, and
cooling of the bioabsorbable fiber.
31. A method of making a device of a reinforced composite of
bioabsorbable fibers, comprising the steps of: a. providing a
plurality of bioabsorbable fibers, comprising: a core of a
semicrystalline fiber-forming bioabsorbable core polymer with a
crystalline core melting temperature, and a sheath of an amorphous
bioabsorbable sheath polymer with a softening point below the
crystalline core melting temperature, wherein the core polymer and
sheath polymer are separately melt extruded, and the sheath is
connected to the core through an adhesive bond; b. providing an
injection mold having interior walls which define an interior
cavity; c. inserting the plurality of bioabsorbable fibers into the
interior cavity of the injection mold; and d. adding a
bioabsorbable injection molding resin polymer to the injection mold
at an injection temperature which is lower than the crystalline
core melting temperature.
32. The method of making a device of claim 31, wherein the
plurality of bioabsorbable fibers provided in step (a) is provided
in a form selected from the group consisting of: knitted, woven,
braided, and in the form of a fabric constructed from the
bioabsorbable fibers.
33. The method of making a device of claim 31, wherein the interior
walls of the injection mold define an interior cavity which is
tubular in shape.
34. The method of making a device of claim 33, wherein the
injection mold further comprises a mandrel, which is present in the
interior cavity during the injection step.
35. The method of making a device of claim 34, wherein the
plurality of fibers are wrapped or wound about the mandrel in step
(c), such that the resulting device has a tubular shape, with
bioabsorbable fibers on the internal surface of the tube.
36. The method of making a device of claim 34, retractable are
inserted into the mandrel, and the bioabsorbable fibers are wound
or woven onto the pins in step (c), such that the bioabsorbable
fibers form a cage structure within the interior of the resulting
device.
37. The method of claim 31, wherein the interior cavity of the
injection mold is configured to provide the device with external
threads.
38. The method of claim 31, wherein the core polymer of the
bioabsorbable fiber provided in step (a) is selected from the group
consisting of poly(L-lactide), polyglycolide,
poly(epsilon-caprolactone), polydioxanone, poly(ester-amide)s, any
combination thereof, and any copolymers thereof wherein
trimethylene carbonate is a comonomer.
39. The method of claim 31, wherein the sheath polymer of the
bioabsorbable fiber provided in step (a) is selected from the group
consisting of poly(ester-amide)s, tyrosine-derived polycarbonates,
poly(trimethylene carbonate), poly(dl-lactide), polydioxanone, and
any copolymer, mixture, or blend thereof.
40. The method of claim 31, wherein the sheath polymer comprises a
copolymer which is the product of copolymerization of at least two
monomers selected from the group of monomers consisting of
epsilon-caprolactone, trimethylene carbonate, L-lactide,
dl-lactide, glycolide, and para-dioxanone.
41. The method of making the device of claim 31, wherein the core
polymer is poly(L-lactide), the sheath polymer is a copolymer of
trimethylene carbonate and L-lactide, and the injection molding
resin is poly(trimethylene carbonate).
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application claims the benefit of U.S. Provisional
Application No. 60/070,610, filed Jan. 6, 1998.
STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT
[0002] Not Applicable
FIELD OF THE INVENTION
[0003] This invention relates to synthetic bioabsorbable fibers.
The present invention also relates to methods of making
bioabsorbable fibers from at least two different polymers by
separately melt extruding the at least two different polymers and
bonding the extruded polymers together to form a fiber with a
semicrystalline polymer core and an amorphous polymer sheath. The
invention also relates to reinforced composites, made at least in
part from synthetic bioabsorbable fibers. Finally, the present
invention relates to devices comprised of such reinforced
composites, wherein the devices are designed for use as in vivo
implants, including implants which can support high loads, such as
for use in fracture fixation and spinal fusion.
BACKGROUND OF THE INVENTION
[0004] Metal implants have a long history of successful use in
orthopedic surgery but also carry many risks for complications. In
the case of metal rods and plates for fracture fixation, a second
surgery for device removal is recommended about one year after
confirmation of osseous union. If the device is not removed the
bone can remodel into a weakened condition due to stress shielding.
There is also the potential for an increased risk of infection. In
the case of metal cages for spinal fusion, complications due to
migration, infection, corrosion, reduced bone density, non-union,
and fracture are especially serious since major surgery is required
for device removal.
[0005] Poly(lactic acid) has been the subject of continuous
research as a material for use in surgical devices since it was
first proposed for this purpose in the mid 1960s. Since poly(lactic
acid) is ultimately hydrolyzed into lactic acid, a normal
intermediate carbohydrate metabolism in man, it continues to be
viewed as the ideal implantable material from the standpoint of
toxicological safety.
[0006] High strength and high modulus fibers produced from
semicrystalline poly(L-lactic acid), also known as poly(lactide),
hereinafter referred to as PLA, have been studied as braided
implants for use as a ligament augmentation device. PLA fibers are
known to be capable of retaining about 70% of their initial tensile
strength after 10 months in vivo.
[0007] In spite of the excellent strength retention of PLA fibers
in vivo, molded articles made from PLA have generally failed to
achieve commercial success as orthopedic implants. The physical
properties of a polymer in fiber form resulting from optimum
drawing and annealing of the fiber cannot be duplicated in the same
polymer processed by injection molding. Thus injection molded PLA
typically may have a tensile strength of 60 MPa. This value may be
increased up to about 300 MPa by stressing the injection molded
parts to achieve orientation prior to crystallization. Highly drawn
PLA fibers, on the other hand, can give tensile strength in excess
of 2,000 MPa.
[0008] One possibility for obtaining fiber strength in a molded
part would be to incorporate PLA fibers into a matrix of PLA or a
similar polymer such as poly(dl-lacitc acid) which is totally
amorphous. The problem with using poly(dl-lacitc acid) is that it
degrades too rapidly for orthopedic applications. Pure
self-reinforced PLA fiber composites have been made by sintering
together bundles of PLA fibers thereby sacrificing some of the
fibers to produce a molten matrix for embedding the remaining
fibers. This process is difficult to control and yields unreliable
results. It also tends to produce a substantial amorphous phase
that can slowly recrystallize upon prolonged storage to give a
brittle, non-reinforcing structure. Moreover, even if
recrystallization is suppressed by copolymerization of L-lactide
with small amounts of dl-lactide, degradation of the amorphous PLA
tends to result in the build-up of acidic degradation products in
the interior of the molded device resulting in an autocatalytic
acceleration of the hydrolytic degradation process.
[0009] Fiber reinforced composites of PLA with the use of other
bioabsorbable polymers as a matrix have generally failed to achieve
adequate in vivo performance due to moisture penetration into the
interface between fiber and matrix. This typical mode of failure
has been the principal problem with all approaches to fully
bioabsorbable composites of the prior art.
BRIEF SUMMARY OF THE INVENTION
[0010] In one aspect, the present invention is a bioabsorbable
fiber comprising a core of a semicrystalline fiber-forming
bioabsorbable core polymer with a crystalline core melting
temperature, and a sheath of an amorphous bioabsorbable sheath
polymer with a softening point below the crystalline core melting
temperature, wherein the core polymer and sheath polymer are
separately melt extruded, and the sheath is connected to the core
through an adhesive bond.
[0011] In another aspect, the present invention is a reinforced
composite, comprising a plurality of filaments of the bioabsorbable
fiber and a molding resin reinforced therewith.
[0012] In yet another aspect, the present invention is a device
designed for in vivo implantation or insertion, fabricated from the
reinforced composite.
[0013] In a further aspect, the present invention is a method of
making the bioabsorbable fiber, comprising the steps of:
[0014] a. selecting a core polymer which is semicrystalline,
fiber-forming, and bioabsorbable, with a crystalline core melting
temperature;
[0015] b. selecting a sheath polymer which is bioabsorbable, and
which forms an amorphous phase on polymerization, with a softening
point below the crystalline core melting temperature;
[0016] c. separately melt extruding the core polymer and sheath
polymer; and
[0017] d. forming an adhesive bond between the core polymer and
sheath polymer, such that the resulting bioabsorbable fiber
comprises a core of the core polymer and a sheath of the sheath
polymer.
[0018] Finally, in yet another aspect, the present invention is a
method of making a surgical device of a reinforced composite of
bioabsorbable fibers, comprising the steps of:
[0019] a. providing a plurality of the bioabsorbable fibers;
[0020] b. providing an injection mold having interior walls which
define an interior cavity;
[0021] c. inserting the plurality of bioabsorbable fibers into the
interior cavity of the injection mold; and
[0022] d. adding a bioabsorbable injection molding resin polymer to
the injection mold at an injection temperature which is lower than
the crystalline core melting temperature.
DETAILED DESCRIPTION OF THE INVENTION
[0023] A. Definitions:
[0024] The following terms used herein shall have the following
definitions:
[0025] "Poly(ester-amide)" shall mean to include any of the
polymers described in U.S. Pat. No. 4,343,931, "Synthetic
Absorbable Surgical Devices of Poly(esteramides)", T. H. Barrows,
Aug. 19, 1982, the teachings of which are incorporated herein by
reference, and to include any of the polymers described in
Provisional Patent Application Serial No. 60/062,064,
"Bioabsorbable Triglycolic Acid Poly(ester-amide)s", T. H. Barrows,
filed Oct. 16, 1997, the teachings of which are incorporated herein
by reference.
[0026] "Tryosine-derived polycarbonates" shall mean to include any
of the polymers described in U.S. Pat. No. 5,198,507, "Synthesis of
Amino Acid-derived Bioerodible Polymers", J. B. Kohn and S. K. K.
Pulapura, Mar. 30, 1993, the teachings of which are incorporated
herein by reference.
[0027] "PLA" shall mean poly(L-lactide).
[0028] "PGA" shall mean polyglycolide.
[0029] "PEA" shall mean poly(ester-amide).
[0030] "TMC" shall mean trimethylene carbonate.
[0031] "Softening point" shall mean the temperature range below
which a polymer is non-tacky and non-self-adherent and above which
the polymer is tacky and self-adherent.
[0032] "Melting temperature" shall mean the crystalline core
melting transition temperature (Tm) of a semi-crystalline
polymer.
[0033] "Injection temperature" shall mean the minimum temperature
of a molten polymer that allows it to have adequately low viscosity
under pressure to flow into an injection mold cavity containing
multifilament fibers such that the spaces between the fibers are
completely filled with the injected molten polymer.
[0034] "Bioabsorbable" shall mean the property of a composition,
material, or device, that allows it to degrade post-implantation
completely into non-toxic degradation products that are eliminated
from the body or are transformed into normal metabolites utilized
within the body.
[0035] B. Bioabsorbable Fibers
[0036] The present invention provides fibers fabricated by a
core-sheath coextrusion process in which two different
bioabsorbable polymers are separately melt extruded and forced into
a single die such that the resultant filaments are comprised of one
polymer substantially at the core and the other polymer
substantially as a sheath. The core polymer is preferably a
semi-crystalline, high strength fiber-forming polymer and the
sheath polymer is preferably a normally amorphous polymer with a
softening point well below the crystalline melting temperature of
the core polymer (hereinafter, the "crystalline core melting
temperature"). The sheath polymer also preferably has a softening
point high enough that it is tack-free at the temperatures required
for optimum hot drawing and annealing of the core fiber.
[0037] The two polymers must be capable of forming an adequate
adhesive bond between them such that when the molten filament is
solidified by cooling and subsequently hot stretched, the sheath
polymer will elongate with the core polymer and not separate from
the core. The coextrusion process in which the two polymers come
into contact with each other in the molten phase provides the
optimum environment needed for the development of an interfacial
bond that will tolerate said processing without failure. Thus an
important feature of the present invention is the discovery that
dissimilar bioabsorbable polymers that normally would not adhere to
each other by hot pressing the two polymers as pre-formed solid
articles adhere well as a result of an intimate interface created
during coextrusion.
[0038] A further advantage of the present invention is that sheath
polymers can be selected from a wide variety of known bioabsorbable
polymers as well as from custom formulated blends and or custom
synthesized copolymers. Sheath polymers are preferably selected
which have a softening point value which ensures subsequent
processing of the core component filaments to produce high strength
fibers. Sheath polymers are also preferably selected to optimize
the integrity of adhesion between the sheath and the core, by
minimizing the penetration of moisture into the interface between
the sheath and core, and by ensuring moisture penetration into the
interface between the sheath and core does not occur at a rate
faster than moisture penetration into the bulk of the sheath
polymer.
[0039] Said fibers ideally are fine multifilaments since it is
known in the art of fiber spinning that maximum draw ratio and
therefore maximum tensile strength and modulus are achieved more
readily with small rather than large diameter fibers. In addition,
multifilament yarns are more versatile in subsequent device
fabrication processing steps than monofilament fiber.
[0040] Fibers of the present invention are comprised of a core of
one bioabsorbable polymer, the "core polymer", and a partial or
complete sheath of a second bioabsorbable polymer, the "sheath
polymer". The core polymer is preferably selected from the group
consisting of poly(L-lactide), polyglycolide,
poly(epsilon-caprolactone), polydioxanone, poly(ester-amide)s, and
any combination of copolymers of said polymers including copolymers
made with the use of trimethylene carbonate and or dl-lactide as
comonomers. The sheath polymer is preferably selected from the
group consisting of poly(ester-amide)s, tyrosine-derived
polycarbonates, poly(trimethylene carbonate), poly(dl-lactide),
polydioxanone, poly(epsilon-caprolactone), and copolymers,
mixtures, and blends of these polymers. Alternatively, the sheath
polymer is the product of copolymerization of any two or more
monomers selected from the group comprised of epsilon-caprolactone,
trimethylene carbonate, L-lactide, dl-lactide, glycolide, and
para-dioxanone.
[0041] The specific core and sheath polymers suitable for inclusion
in a given biocomponent fiber of the present invention depends upon
the intended use for the particular biocomponent fiber. For
example, if the fiber is to be used to fabricated a device for
implantation into bone, the preferred core polymer is PLA and the
preferred sheath polymer is selected from the group comprised of
polyTMC, poly(TMC-co-L-lactide), poly(TMC-co-epsilon-caprolactone),
tyrosine-derived polycarbonates, and PEAs.
[0042] The preferred core polymer for fracture fixation and spinal
fusion devices is PLA due to its high strength, stiffness, and
long-lasting strength retention. The slow degradation time of
crystalline PLA fibers is not anticipated to result in the release
of excessively acidic degradation products due to the long time
course of degradation. The sheath polymer and the molding resin
polymer, on the other hand, preferably are not PLA or PLA/PGA
copolymers since the release of acidic degradation products and the
autocatalytic acceleration of the degradation process mentioned
previously are possible drawbacks. Instead, polycarbonates such as
polyTMC, polyTMC copolymers, and tyrosine-derived polycarbonates as
well as certain PEAs are preferred since they degrade slowly, are
relatively hydrophobic, and do not release a significant amount of
acidic degradation products.
[0043] Triglycolic acid PEAs are especially preferred as sheath
polymers and as molding resin polymers since they provide
exceptionally good inter-fiber adhesion due to their "hot melt"
adhesive properties. A further advantage of triglycolic acid PEAs
is that they can be block copolymerized with PLA to provide a
strong intermolecular interaction with the molten PLA core during
coextrusion and thus provide an interfacial bond between core and
sheath that is highly resistant to premature moisture penetration.
Similarly, TMC can be randomly or block copolymerized with lactide
or caprolactone both to increase the softening point of pure
polyTMC and to improve its compatibility as a sheath polymer with
the PLA core during the coextrusion process. Pure polyTMC of an
appropriate molecular weight may be a suitable injection molding
resin polymer due to its low injection temperature, slow
degradation rate, hydrophobic nature, and non-acidic degradation
products.
[0044] C. Production of Reinforced Composites
[0045] The biocomponent fibers of the present invention can be
processed into reinforced composites by a number of different
methods. A preferred method is injection molding. Thus short (e.g.
1-10 mm) chopped fibers can be added to a molding resin polymer
such that the "filled" molding resin contains about 10 to 70% of
reinforcement fibers by volume.
[0046] Alternatively the injection molding cavity can be pre-loaded
with a fabric of said fibers in continuous form and injected with
an injection molding resin polymer selected from any of the
polymers in the group identified above as sheath polymers. The
injection molding resin polymer may be the same polymer as the
sheath polymer of the continuous fibers or a different polymer.
Optionally, the injection molding resin polymer also may be
"filled" with a reinforcement filler in the form of short fibers of
the present invention and or a mineral filler such as
hydroxyapatite. Mineral fillers also optionally may be pre-treated
with coupling reagents such as silane coupling agents known in the
prior art to provide improved bonding to injection molding resin
polymers.
[0047] D. Production of Devices of the Reinforced Composites:
[0048] Production of devices of the reinforced composites of the
present invention can be achieved most conveniently by injection
molding with a molding resin that is "filled" with the above fibers
cut into short lengths. The molding resin can be the same polymer
as the sheath polymer or a polymer of similar composition such that
excellent adhesion is obtained between the molding resin and the
sheath of the reinforcing fiber. The injection temperature of the
molding resin may be higher or lower than the softening temperature
of the sheath polymer, but must be below the melting temperature of
the core polymer.
[0049] An especially advantageous use for the bioabsorbable fibers
of the present invention is in the fabrication of high strength
tubular implants for use as intramedullary rods for fracture
fixation and as cage implants for spinal fusion. Thus the
biocomponent fibers are first tightly wrapped around a mandrel in
multiple layers with a ply angle of about 45 degrees. The fiber
covered mandrel then serves as the core of an injection mold cavity
which is injected with the appropriate bioabsorbable polymer to
obtain a solid, fiber reinforced tubular device. The bending
strength of the tubular device is determined by the wall thickness
which can be varied by varying the diameter of the mandrel or the
dimensions of the injection molding cavity. The external surface of
the device can be provided with any desired texture or added
features such as parallel flutes for implant stabilization by
proper design of the mold cavity.
[0050] Similarly, a threaded, perforated, spinal fusion cage can be
fabricated by inserting retractable pins into the mandrel core of
the mold cavity and winding fibers at a lower ply angle (e.g. about
30 degrees) such that the fibers are aligned more closely with the
axis of the mandrel and are woven between the pins. The pins serve
both to prevent the fibers from shifting during injection molding
and to provide perforations in the device needed for autologous
bone graft placed by the surgeon in the "cage" to grow out into the
surrounding space. Alternatively, a loosely woven fabric of the
biocomponent fibers can be wrapped many times around the mandrel
with protruding removable pins such that the fibers separate enough
to allow the pins to pass through the fabric. In this way most of
the fibers can be aligned completely parallel with the axis of the
mandrel which is the direction in greatest need of reinforcement if
the device is implanted parallel to the spinal column. Upon
clamping the mold and injecting it with the appropriate
bioabsorbable polymer molding resin, cooling, parting the mold,
extracting the pins, and retracting the mandrel core, the finished
part will be a solid fiber reinforced tube with perforations in the
wall corresponding to the number and size of the pins. The external
surface of the device can be provided with any desired texture or
added features such as threads for implant stabilization by proper
design of the mold cavity.
[0051] The molding resin optionally can be modified by the addition
of other additives such as finely divided mineral such as
hydroxyapatite to improve the hardness of the molding resin. This
could be especially useful in the case of the threaded spinal
fusion cage since the mineral would tend to be filtered out of the
fiber containing portion of the mold and concentrated in the open
cavities that form the threads where it is most needed. PEA is an
especially preferred molding resin for use with a mineral filler
since the nylon like character of PEA ensures good adhesion of the
polymer to the filler if a silane coupling agent such as
trimethoxyaminopropyl silane is used to pre-treat the mineral
filler.
[0052] The spinal fusion devices of the present invention, produced
as described above, function in a manner similar to commercially
available titanium fusion cages. These cages are packed with
autologous bone chips which eventually regenerate new bone that
grows through the holes in the cylinder walls as well as through
the open ends of the tube thereby bridging or "fusing" the adjacent
vertebral bodies. A superior long term result is anticipated with
fully bioabsorbable devices of the present invention since the
implant gradually transfers loads onto the new bone thereby
stimulating it to remodel into denser, more functional tissue.
Ultimately the fully bioabsorbable device of the present invention
will be completely replaced with new bone that can remodel into
normal healthy tissue.
[0053] Other thinner more flexible tubular devices such as stents
can be produced from fibers of the present invention by placing
woven, nonwoven, knitted, or braided fabric or mesh around a
mandrel and injection molding. Upon cooling and removing the
mandrel, a tubular stent with the desired degree of stiffness and
porosity (imparted by the surface topography of the mold cavity or
mandrel core) will be obtained. Such stents are useful in a variety
of surgical applications such as in the urinary tract, bile duct,
and peripheral nerves. The fibrous nature of the composite ensures
good suture holding strength in thin walled constructions.
[0054] Other methods of processing fibers of the present invention
into composite structures and other uses for such composite
materials will be apparent to those skilled in the art of fiber
processing and surgical device fabrication.
EXAMPLES
[0055] The following examples are given to illustrate various
aspects of the invention, without limiting the scope thereof:
Example 1
Bicomponent Fiber of PLA Core and Poly(TMC-co-L-lactide) Sheath
[0056] A copolymer of TMC and L-lactide is prepared from a mixture
of L-lactide and TMC by heating under an inert atmosphere and
anhydrous conditions with stirring in the presence of stannous
octoate as a catalyst and lauryl alcohol as an initiator. The ratio
of L-lactide to TMC is adjusted so that the resulting high
molecular weight polymer has a softening point below the
crystalline melting point of PLA (e.g. about 180.degree. C.) and
above the temperature needed to hot stretch and anneal PLA fibers
(e.g. about 90-110.degree. C.).
[0057] PLA and the above poly(TMC-co-L-lactide) polymers are
separately melt extruded into a single specially designed
multifilament core-sheath spinneret. The ratios of polymers are
adjusted such that the core is 60-90% by volume and the sheath is
40-10% by volume. After maximum drawing, the fiber tow is annealed
to give high tensile strength, high modulus fibers that are in the
size range of 3-20 denier per filament.
Example 2
Bicomponent Fiber of PLA Core and Poly(TMC-co-epsilon-caprolactone)
Sheath
[0058] A core-sheath polymer fiber is produced as described in
Example 1 except that TMC and epsilon-caprolactone are
copolymerized in the appropriate ratio to obtain a sheath polymer
with the proper softening point for use in coextrusion with
PLA.
Example 3
Bicomponent Fiber of PLA Core and Poly(TMC-co-para-dioxanone)
Sheath
[0059] A core-sheath polymer fiber is produced as described in
Example 1 except that TMC and para-dioxanone are copolymerized in
the appropriate ratio to obtain a sheath polymer with the proper
softening point for use in coextrusion with PLA.
Example 4
Bicomponent Fiber of PLA core and PEA Sheath
[0060] A core-sheath polymer fiber is produced as described in
Example 1 except that
poly[2,5-dioxahexane-1,6-di(carbonyloxy)hexane-1,6-di
(amidocarbonylpentamethylene)], prepared as described in
Provisional Patent Application by T. H. Barrows entitled,
"Bioabsorbable Triglycolic Acid Poly(ester-amide)s", filed Oct. 16,
1997, is used for coextrusion with PLA.
Example 5
Bicomponent Fiber of PLA Core and PEA-co-block-PLA Sheath
[0061] A core-sheath polymer fiber is produced as described in
Example 4 except that the sheath polymer is further reacted with
L-lactide to form a block copolymer. This block copolymer is
described in Provisional Patent Application by T. H. Barrows
entitled, "Bioabsorbable Triglycolic Acid Poly(ester-amide)s",
filed Oct. 16, 1997. This sheath polymer is used for coextrusion
with PLA.
Example 6
Bicomponent Fiber of PLA Core and Tyrosine-Derived Polycarbonate
Sheath
[0062] A core-sheath polymer fiber is produced as described in
Example 1 except that poly(DTH carbonate) prepared as described in
U.S. Pat. No. 5,198,507 is used for coextrusion with PLA.
Examples 7 through 12
Bicomponent Fibers of PGA Core
[0063] The bicomponent fibers of Examples 1 through 6,
respectively, are produced in a similar manner except that PGA is
used instead of PLA as the core polymer. The sheath polymers in
Examples 7 and 11 are copolymers made with the substitution of
glycolide for lactide.
Example 13
Bicomponent Fibers of PGA Core and Poly(dl-lactide) Sheath
[0064] The bicomponent fibers of Example 1 are produced in a
similar manner except that PGA is used instead of PLA as the core
polymer and poly(dl-lactide) is used as the sheath polymer.
Example 14
Bioabsorbable Biocomponent Fiber Reinforced Injection Molding
Resins
[0065] Biocomponent fibers prepared as described in any of the
above Examples 1-13 are cut into 1-3 mm lengths and melt blended
with 30 to 90% by volume of the corresponding sheath polymer and
extruded at a temperature below the melting temperature of the core
polymer into a 3-6 mm diameter strand, cooled, and cut into pellets
with a cutting machine to produce pelletized fiber filled resin for
injection molding.
Example 15
Bioabsorbable Biocomponent Fiber Reinforced Insert Injection Molded
Spinal Fusion Cage
[0066] A loosely woven or knitted fabric in the form of a 3 cm wide
continuous strip is produced from any of the fibers in Examples 1
through 6. This fabric is wound around a mandrel that is 7 mm in
diameter and features an equally spaced array of 24 protruding 3 mm
diameter pins over a central 3 cm length such that the open spaces
in the fabric allow the pins to pass through the fabric. The fabric
is then tightly wound on the surface of the mandrel to build up a 4
mm thick layer of fabric. The mandrel thus prepared is inserted
into a specially design injection molding cavity that both mates
with the pins and has an inner surface that produces an outer
surface for the resultant molded part that features 1 by 3 mm
threads.
[0067] With the mold properly clamped it is then injected with
molten polymer that has approximately the same composition as the
sheath polymer in the reinforcement fibers. The injection molding
resin polymer preferably has a low injection temperature and low
viscosity to ensure complete impregnation of the reinforcement
fabric. Upon completion of the molding cycle, the mold is parted,
the pins are extracted, and the part is ejected by retraction of
the core. The resultant injection molded part is an open tube
approximately 3 cm long and approximately 15 mm in diameter with
threads on the external surface and 24 equally spaced 3 mm diameter
holes passing through the wall of the tube.
[0068] The bioabsorbable fiber reinforced spinal fusion cage
described above can be utilized to bridge and fuse adjacent
vertebrae in the same manner as commercially available titanium
fusion cages. Thus two such cages are filled with autologous bone
chips and threaded into separate predrilled and tapped holes
created in the surfaces of the adjacent vertebrae facing the space
created by removal of the disc. Unlike the metal implants, however,
the fusion cage of this example is fully bioabsorbable. Thus over
time after the graft of bone chips "takes" and heals, the implant
slowly weakens due to degradation and gradually transfers
mechanical loads onto the new bone, thereby stimulating it to
remodel into a stronger, denser, more functional tissue than is
possible for a bone graft confined in a metal implant. Ultimately
the fusion cage of this example is bioabsorbed and eliminated from
the body, thereby creating additional space for the regeneration of
more new bone.
Example 16
Bioabsorbable Biocomponent Fiber Reinforced Insert Injection Molded
Spinal Fusion Cage Containing Hydroxyapatite Reinforcement
Filler
[0069] The bioabsorbable fusion cage of Example 15 is produced in a
similar manner except that the injection molding resin is "filled"
with 10 to 70% by volume of hydroxyapatite mineral in finely
divided form, preferably surface treated with a coupling agent such
as trimethoxyaminopropyl silane to promote adhesion of the mineral
filler with the injection molding resin polymer. This filler
provides a device with greater hardness and strength. It also
reduces the volume of bioabsorbable polymer in the implant and
replaces it with a mineral that is normally present in bone and
will be incorporated into the new bone that is formed upon
bioabsorption of the implant. Although the fabric may act as a
filter and prevent filler from entering the spaces between the
fibers, this would result in the filler being concentrated in the
threads of the device where would be most useful.
Example 17
Bioabsorbable Biocomponent Fiber Reinforced Insert Injection Molded
Tubular Stent
[0070] A PGA core biocomponent fiber selected from those described
in Examples 7 through 13 is used to fabricate a knitted or woven
fabric. The fabric is wrapped around a mandrel that forms the core
of an injection molding cavity. The mold is then injected with
molten polymer selected for any of the above mentioned sheath
polymers. Upon cooling, parting the mold, and retracting the core,
a thin walled, semi-rigid tube with good suture holding properties
is formed that can be used as a stent for peripheral nerve
grafting, bile duct reconstruction, and in ureter and urethra
reconstruction.
* * * * *