U.S. patent application number 09/983537 was filed with the patent office on 2002-04-25 for in situ bioprosthetic filler and methods, particularly for the in situ formation of vertebral disc bioprosthetics.
Invention is credited to Black, Kirby S., Walsh, Steven P., Yuksel, K. Umit.
Application Number | 20020049498 09/983537 |
Document ID | / |
Family ID | 22914850 |
Filed Date | 2002-04-25 |
United States Patent
Application |
20020049498 |
Kind Code |
A1 |
Yuksel, K. Umit ; et
al. |
April 25, 2002 |
In situ bioprosthetic filler and methods, particularly for the in
situ formation of vertebral disc bioprosthetics
Abstract
Bioprosthetic devices include an exterior biological tissue
member which at least partly defines a cavity, and a proteinaceous
biopolymer which fills the cavity, and intercalates and is
chemically bound (fixed) to the tissue of the surrounding
biological tissue member. In preferred forms, the bioprosthetic
device is a bioprosthetic vertebral disc having a fibrillar outer
annulus which surrounds and defines an interior cavity and is
formed by removal of at least a substantial portion of the natural
gelatinous core therefrom. The cavity defined by the fibrillar
outer annulus may then be filled with a flowable proteinaceous
biopolymer. Preferably, the proteinaceous biopolymer is a liquid
mixture comprised of human or animal-derived protein material and a
di- or polyaldehyde, which are allowed to react in situ to form a
cross-linked biopolymer within the cavity. The liquid mixture may
be formed in advance of being introduced into the cavity, or may be
formed simultaneously during introduction into the cavity.
Inventors: |
Yuksel, K. Umit; (Kennesaw,
GA) ; Walsh, Steven P.; (Marietta, GA) ;
Black, Kirby S.; (Achworth, GA) |
Correspondence
Address: |
NIXON & VANDERHYE P.C.
8th Floor
1100 North Glebe Road
Arlington
VA
22201
US
|
Family ID: |
22914850 |
Appl. No.: |
09/983537 |
Filed: |
October 24, 2001 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
60242457 |
Oct 24, 2000 |
|
|
|
Current U.S.
Class: |
623/17.16 ;
623/17.12 |
Current CPC
Class: |
A61L 27/18 20130101;
C08L 71/02 20130101; A61L 27/3658 20130101; A61L 27/3691 20130101;
A61F 2002/4445 20130101; A61L 27/18 20130101; A61L 27/227 20130101;
A61F 2002/445 20130101; A61L 27/3604 20130101; A61L 27/22 20130101;
A61L 27/40 20130101 |
Class at
Publication: |
623/17.16 ;
623/17.12 |
International
Class: |
A61F 002/44 |
Claims
What is claimed is:
1. The combination comprised of an exterior biological tissue
member which at least partly defines a cavity, and a polymeric
material which fills the cavity, intercalates the surrounding
biological tissue member, and is chemically bound to the tissue of
the surrounding biological tissue member.
2. The combination of claim 1, wherein the polymeric material is a
proteinaceous biopolymer.
3. The combination of claim 1, wherein the polymeric material
includes a fibrous or particulate filler material.
4. The combination of claim 2, wherein the biopolymer is the
cross-linked reaction product of human or animal-derived protein
material and a di- or polyaldehyde.
5. The combination of claim 4, wherein the protein is bovine or
human serum albumin or hemoglobin.
6. The combination of claim 5, wherein the aldehyde is
glutaraldehyde.
7. The combination of any one of claims 1-6, in the form of a
vertebral disc.
8. The combination of claim 7, wherein the vertebral disc which
remains intact and flexible after being subjected to 5 million
cycles of a cyclic load of 0.85 MPa.
9. The combination of claim 2, wherein the proteinaceous biopolymer
is the reaction product of at least two reactable components, and
wherein one of the components includes a natural, synthetic or
sequence-modified polypeptide.
10. The combination of claim 1, wherein the polymeric material is
the reaction product of at least two reactable components, and
wherein one of the components includes a synthetic polymeric
component which contains a cross-linkable functional group.
11. The combination of claim 10, wherein the synthetic polymeric
components includes polyethylene glycol polymer derivatized with
electrophilic and/or nucleophilic groups.
12. The combination of claim 11, wherein the electrophilic and/or
nucleophilic groups include at least one selected from amine,
succinimidyl, anhydride and thiol groups.
13. A bioprosthetic vertebral disc comprised of a fibrillar outer
annulus which remains following removal of a gelatinous core from a
biologically natural vertebral disc to thereby define an interior
cavity, and a proteinaceous biopolymer which fills the cavity and
intercalates the surrounding biological tissue of the fibrillar
outer annulus.
14. The bioprosthetic vertebral disc of claim 13, that exhibits
flexibility comparable to the biologically natural vertebral
disc.
15. The bioprosthetic vertebral disc of claim 14, that exhibits
flexibility comparable to the biologically natural vertebral disc
after being subjected to 5 million cycles of a cyclic load of 0.85
MPa.
16. The bioprosthetic vertebral disc of claim 14, wherein the
biopolymer includes a fibrous or particulate filler material.
17. The bioprosthetic vertebral disc of claim 13, wherein the
biopolymer is the cross-linked reaction product of human or
animal-derived protein material and a di- or polyaldehyde.
18. The bioprosthetic vertebral disc of claim 17, wherein the
protein is bovine or human serum albumin or hemoglobin.
19. The bioprosthetic vertebral disc of claim 17 or 18, wherein the
aldehyde is glutaraldehyde.
20. A method for the in situ formation of a bioprosthetic device
comprising filling a cavity defined at least partly by surrounding
biological tissue material with a flowable polymeric material in
situ within the cavity thereby forming the bioprosthetic
device.
21. The method of claim 20, which comprises injecting a flowable
proteinaceous biopolymer into the cavity, and allowing the
proteinaceous biopolymer to at least partly solidify in situ
therewithin.
22. The method of claim 20, said method comprises injecting at
least two reactable biopolymeric components in situ within the
cavity, and allowing the reactable biopolymeric components at least
partly solidify by a cross-linkage reaction therebetween.
23. The method of claim 21, wherein said at least two reactable
components are premixed before being injected into the cavity.
24. The method of claim 21, wherein said at least two reactable
components are mixed simultaneously while being injected into the
cavity.
25. The method of claim 21, wherein said at least two reactable
components include a liquid mixture comprised of human or
animal-derived protein material and a di- or polyaldehyde, and
wherein the method comprises allowing the liquid mixture to form a
cross-linked proteinaceous biopolymer material in situ within the
cavity.
26. The method of claim 25, wherein said protein material and said
di- or polyaldehyde are premixed before being introduced into the
cavity.
27. The method of claim 25, wherein said protein material and said
di- or polyaldehyde are mixed simultaneously while being introduced
into the cavity.
28. The method of claim 25, which includes providing a fibrous or
particulate filler material in the liquid mixture.
29. The method of claim 21, wherein the proteinaceous biopolymer is
the reaction product of at least two reactable components, and
wherein one of the components includes a natural, synthetic or
sequence-modified polypeptide.
30. The method of claim 20, wherein the polymeric material is the
reaction product of at least two reactable components, and wherein
one of the components includes a synthetic polymeric component
which contains a cross-linkable functional group.
31. The method of claim 30, wherein the at least one of the
reactable components includes polyethylene glycol polymer
derivatized with electrophilic and/or nucleophilic groups.
32. The method of claim 31, wherein the electrophilic and/or
nucleophilic groups include at least one selected from amine,
succinimidyl, anhydride and thiol groups.
33. A method for the formation of a bioprosthetic vertebral disc
comprising: (a) providing a vertebral disc having a fibrillar outer
annulus which surrounds and defines an interior cavity formed by
removal of at least a substantial portion of a gelatinous core
therefrom; (b) filling the cavity defined by the fibrillar outer
annulus with a flowable polymeric material, and (c) allowing the
polymeric material to at least partly solidify in situ within the
cavity.
34. The method of claim 33, wherein the polymeric material is a
proteinaceous biopolymer.
35. The method of claim 33, said method comprises injecting at
least two reactable biopolymeric components in situ within the
cavity, and allowing the reactable biopolymeric components at least
partly solidify by reaction therebetween.
36. The method of claim 35, wherein said at least two reactable
components are premixed before being injected into the cavity.
37. The method of claim 35, wherein said at least two reactable
components are mixed simultaneously while being injected into the
cavity.
38. The method of claim 35, wherein said at least two reactable
components include a liquid mixture comprised of human or
animal-derived protein material and a di- or polyaldehyde, and
wherein the method comprises allowing the liquid mixture to form a
cross-linked proteinaceous biopolymer material in situ within the
cavity.
39. The method of claim 38, wherein said protein material and said
di- or polyaldehyde are premixed before being introduced into the
cavity.
40. The method of claim 38, wherein said protein material and said
di- or polyaldehyde are mixed simultaneously while being introduced
into the cavity.
41. The method of claim 38, which includes providing a fibrous or
particulate filler material in the liquid mixture.
42. The method of claim 33, wherein prior to step (a) there is
practiced the step of (a1) removing a substantial portion of the
gelatinous core of the vertebral disc to leave the fibrillar outer
annulus which defines the interior cavity.
Description
CROSS-REFERENCE TO RELATED APPLICATION
[0001] The present application is based on, and claims domestic
priority benefits under 35 USC .sctn.119(e) from, copending U.S.
Provisional Application Ser. No. 60/242,457 filed on Oct. 24, 2000,
the entire content of which is expressly incorporated hereinto by
reference.
FIELD OF THE INVENTION
[0002] The present invention relates generally to bioprosthetics.
In especially preferred embodiments, the present invention is
related to bioprosthetics formed in situ.
BACKGROUND AND SUMMARY OF THE INVENTION
[0003] The vertebral disc is a collagenous spacer positioned
between the vertebral bones of the spinal column. The disc
generically consists of a tough fibrillar outer annulus (annulus
fibrosus) and a highly hydrated gelatinous core (nucleus pulposus).
The vertebral disc serves as a shock absorber to dissipate the
energy of impact loading on the back, as well as a joint, allowing
flexion and extension of the human torso.
[0004] Degeneration of vertebral disc function in the lumbar
portion of the spine is the leading cause of debilitating low back
pain in adults over the age of 35. Degenerative disc disease (DDD)
is characterized by a gradual collapse of the vertebral disc due to
dehydration of the nucleus pulposus, or by a bulging of the annulus
fibrosus. DDD may also precipitate the formation of fissures within
the annulus that allows extrusion of the disc nucleus (disc
herniation) resulting in a sudden collapse in the disc height and
the potential for nerve root and/or spinal cord compression. Disc
herniation may also result due to trauma related over compression
of the spine, such as a heavy sitting fall.
[0005] Chronic diffuse low back pain results from irritation of
pain receptors in the outer third of the disc annulus and
surrounding soft tissues as the disc collapses. Radicular pain
results from direct compression of the affected nerve root by
extruded or bulging disc tissue. Aggressive and extensive physical
therapy and drug treatments are the first line treatments for
debilitating back pain. In the absence of acceptable pain
resolution, surgical intervention is indicated.
[0006] The traditional surgical procedures for treatment of
intractable low back pain due to DDD call for either fusion of the
vertebral bodies above and below the affected disc, or removal of
the nuclear material thorough open surgical, micro-surgical or
endoscopic procedures. Recently, novel procedures involving thermal
shrinkage of the collagenous lamina with an electrothermal catheter
or laser device have been applied. The removal of the nucleus
leaves a void within the disc, and eliminates the viscoelastic
fluid that acts as a shock absorber. This void and absence of the
viscoelastic fluid creates an opportunity for the lamina to
collapse inward and allows the disc space to collapse further. The
collapse of the disc space can lead to loss of motion and
morbidity, as during the collapse of the disc space the nerves
radiating from the spinal column may be pinched.
[0007] Many surgical techniques and specialized devices have been
generated to combat the problem of progressive disc collapse
resulting from disc denucleation. Harvested autologous bone has
been placed within the denucleated disc space to afford a bony
bridge or fusion between the two vertebral bodies. Pedicle screws
and other spinal instruments, such as rods and plates, are
mechanically affixed to the vertebral bodies, stabilizing the
vertebra and preventing further collapse. The problem with these,
and other fusion techniques, is the prevention of motion at the
level of repair, and resultant transfer of stresses to the levels
above and below. These additional loading stresses inevitably
result in the degeneration of these disc levels as well.
[0008] The patent literature discloses several apparati for the
replacement of an entire disc (i.e., prosthetic vertebral disc),
whereby the damaged disc is removed and a device is anchored to the
vertebral bone below and above the damaged disc. The ultimate goal
of such a design concept is to maintain or regain the mobility of
the native vertebra-disc-vertebra motion segment. Varying degrees
of mobility have been claimed for different types of mechanical
disc replacements. The following is a non-exhaustive list of such
U.S. Patent disclosures:.sup.1 U.S. Pat. No. 4,309,777 to Patil;
U.S. Pat. No. 5,865,845 to Thalgott; U.S. Pat. No. 5,827,328 to
Buttermann; U.S. Pat. No. 5,865,846 to Bryan et al; U.S. Pat. No.
4,759,766 to Buettner-Jantz et al.; U.S. Pat. No. 5,071,437 to
Steffe; U.S. Pat. No. 4,911,718 to Lee et al.; and U.S. Pat. No.
4,714,469 to Kenna. The utility of these prior design proposals has
been principally limited by an inability to adequately anchor the
flexible prosthetic disc to the bony vertebra. .sup.1 The entire
disclosure of each U.S. Patent cited hereinafter is hereby
expressly incorporated hereinto by reference.
[0009] An alternate approach to the repair of damaged or diseased
vertebral discs is to physically prevent disc collapse through the
insertion of a rigid body into the disc space. The insertion of
tubular or other hollow devices, that may, in addition, contain
openings through their walls to allow bone growth through the
device, enable the motion segment to be fused with the vertebral
spacing maintained. These open or tubular devices may be
constructed of metallic alloys traditional to implantable medical
devices (e.g., stainless steel, titanium and titanium alloys),
carbon fiber reinforced engineering thermoplastics (e.g.,
polyetheretherketones), or machined human cortical bone. These
devices have been disclosed, for example, in U.S. Pat. No.
4,961,740 to Ray et al; U.S. Pat. No. 5,015,247 to Michelson; U.S.
Pat. No. 5,766,253 to Brosnahan; U.S. Pat. No. 5,425,772 to
Brantigan; and U.S. Pat. No. 5,814,084 to Grivas et al. While these
devices may retain the proper spacing between the vertebra (i.e.,
the disc height), they are disadvantageous since, as the two
vertebrae are fused, motion across the vertebra-disc-vertebra
element is eliminated.
[0010] Another general technique for the preservation of vertebral
body separation is to replace the removed disc nuclear tissue with
non-fusing, non-rigid materials. One prior proposal suggests using
a bladder that can be filled with liquid to restore disc height
(see, U.S. Pat. No. 3,875,595 to Froning). One other prior proposal
is disclosed in U.S. Pat. No. 5,534,028 to Bao et al, where a
pre-cast pre-shaped hydrogel in placed into the void. Variations on
the type of device disclosed in Bao et al '028 are likewise
disclosed in U.S. Pat. No. 5,976,186, U.S. Pat. No. 5,192,326, and
U.S. Pat. No. 5,047,055. Preformed inserts made from a xerogel
plastic as a nucleus pulposus replacement have also been disclosed
in U.S. Pat. No. 6,264,695. A cylindrical hydrogel pillow that is
contained within a non-expanding casing and assorted variations
thereof are described in U.S. Pat. No. 4,772,287, U.S. Pat. No.
4,904,260, U.S. Pat. No. 5,674,295, U.S. Pat. No. 5,824,093, and
U.S. Pat. No. 6,022,376. In this regard, the device shown in U.S.
Pat. No. 6,022,376 is inserted into tunnels drilled into the disc
as a dehydrated hydrogel resin, and is allowed to rehydrate and
swell once it is inserted. The swelling holds the device in place
while preventing the collapse of the denucleated disc. However, the
device is neither chemically nor mechanically fixated in place.
[0011] It has also been disclosed in U.S. Pat. No. 6,183,581,
6,206,921 and 6,264,659, that molten gutta percha and its compounds
may be used as possible replacements of nucleus pulposus.
[0012] Broadly, the present invention relates to bioprosthetic
devices comprised of an exterior biological tissue member which at
least partly defines a cavity, and a proteinaceous biopolymer which
fills the cavity, and intercalates is chemically bound (linked) to
the surrounding biological tissue member. In preferred forms, the
bioprosthetic device is a bioprosthetic vertebral disc having a
fibrillar outer annulus which surrounds and defines an interior
cavity and is formed by removal of at least a substantial portion
of the natural gelatinous core therefrom. The cavity defined by the
fibrillar outer annulus may then be filled with a flowable
biopolymeric material which is then allowed to at least partly
solidify in situ (e.g., most preferably by in situ cross-linkage
reaction) to form a proteinaceous biopolymer within the cavity.
[0013] The flowable biopolymeric material is most preferably a
liquid mixture liquid mixture comprised of human or animal-derived
protein material and a di- or polyaldehyde. When introduced into
the cavity of the tissue member, therefore, the liquid mixture may
then react to form a cross-linked biopolymer in situ within the
cavity thereby forming a bioprosthetic device therein. The liquid
mixture may be formed in advance of being introduced into the
cavity, or may be formed simultaneously during introduction into
the cavity.
[0014] These and other aspects and advantages will become more
apparent after careful consideration is given to the following
detailed description of the preferred exemplary embodiments
thereof.
BRIEF DESCRIPTION OF THE ACCOMPANYING DRAWINGS
[0015] Reference will hereinafter be made to the accompanying
drawing FIGURE which schematically depicts a portion of a patient's
vertebral column showing a vertebral disc bioprosthetic in
accordance with the present invention interposed between adjacent
vertebrae.
DETAILED DESCRIPTION OF THE INVENTION
[0016] As used herein and in the accompanying claims, the term
"bioprosthetic device" and like terms mean a combination comprised
of a biological tissue member and a proteinaceous biopolymer which
is chemically bound (linked) to the tissue of the tissue
member.
[0017] The accompanying drawing FIGURE shows a segment of a
patient's vertebral column VC wherein vertebral disc bioprosthetics
10 in accordance with the present invention are interposed between
adjacent ones of the individual vertebrae V. The vertebral disc
bioprosthetics 10 essentially include the fibrillar outer annulus
10-1 of the patient's natural vertebral disc following removal of
the gelatinous core. The fibrillar outer annulus 10-1 thus bounds
and defines an inner cavity into which a proteinaceous biopolymer
10-2 is injected in situ. The proteinaceous biopolymer (usually
referred to hereinafter more simply as the "biopolymer") 10-2 thus
fills completely the void space left following removal of the
natural gelatinous core of the patient's natural vertebral disc.
The biopolymer 10-2 thus acts as a shock-absorber of sorts similar
to the natural functions attributable to the removed gelatinous
core.
[0018] Virtually any suitable proteinaceous biopolymer may be
employed in the practice of the present invention. In this regard,
the term "proteinaceous biopolymer" and like terms mean a polymeric
or copolymeric material which contains one or more units in the
polymer chain comprised of natural, synthetic or sequence-modified
proteins or polypeptides, and mixtures and blends of such polymeric
and/or copolymeric materials.
[0019] One especially preferred biopolymer 10-2 that may be
employed in the practice of this invention is a cross-linked
reaction product of a two part mixture initially comprised of:
[0020] Part A: a water-soluble proteinaceous material of about
27-53% by weight of the mixture, and
[0021] Part B: di- or polyaldehydes present in a weight ratio of
one part by weight to every 20-60 parts of protein present by
weight in the mixture and water, optionally containing
non-essential ingredients to make up the balance of the
composition.
[0022] Part A of the mixture is most preferably substantially an
aqueous solution of a proteinaceous material of human or animal
origin. Albumins including ovalbumins are preferred proteins, and
serum albumins of human or animal origin are particularly
preferred. The proteinaceous material may be a purified protein or
a mixture in which the proteins such as serum albumins are the
predominant ingredients. For example, the solid mixtures obtained
by dehydration of blood plasma or serum, or of commercial solutions
of stabilized plasma proteins, can be used to prepare Part A. These
mixtures, generally referred to as plasma solids or serum solids,
are known to contain albumins as their major ingredients, of the
order of 50-90%. As used herein, the term "plasma" refers to whole
blood from which the corpuscles have been removed by
centrifugation. The term "serum" refers to plasma which has
additionally been treated to prevent agglutination by removal of
its fibrinogen and/or fibrin, or by inhibiting the fibrin clot
formation through addition of reagents, such as citrate or EDTA.
The proteinaceous material may also contain an effective amount of
hemoglobin.
[0023] Part B is substantially an aqueous solution of di- or
polyaldehydes. A wide range of these substances exist, and their
usefulness is restricted largely by availability and by their
solubility in water. For example, aqueous glyoxal (ethandial) is
useful, as is aqueous glutaraldehyde (pentandial). Water soluble
mixtures of di- and polyaldehydes prepared by oxidative cleavage of
appropriate carbohydrates with periodate, ozone or the like are
also useful. Glutaraldehyde is the preferred dialdehyde ingredient
of Part B. When Parts A and B are brought together, the resultant
product rapidly hardens to a strong, flexible, leathery or rubbery
material within a short time of mixing, generally on the order of
15-30 seconds. The most preferred material for use in the present
invention is commercially available from CryoLife, Inc. of
Kennesaw, Ga. under the registered trademark "BIOGLUE". (See also,
U.S. Pat. No. 5,385,606, the entire content of which is expressly
incorporated hereinto by reference.)
[0024] The two components A and B noted above are either premixed
and then applied, or simultaneously mixed and delivered through an
in-line mixing/dispensing tip during the filling of the
tissue-defined cavity. Upon reaction of the two components, the
resulting biomaterial is a hydrogel that adheres to the surrounding
tissue, intercalates into the voids of the surrounding tissues, is
space filling, and is mechanically and biologically stable for some
time. The material may be solid or sponge-like in appearance.
Furthermore, it may contain organic or inorganic salts or other
particulate matter to modify the physical properties of the
resulting bioprosthetic device. Preferably, the biopolymer 10-2
will exhibit compressive strengths of at least 300 kPa (preferably
between about 300 to about 600 kPa) and compressive moduli of 2.5
MPa, and creep moduli of 1.0 MPa. The ultimate compressive strength
of the biopolymer 10-2 can be adjusted by altering the composition
of the protein and cross-linker components and/or through the
addition of various fillers.
[0025] As noted previously, the proteinaceous biopolymer that may
be employed in the practice of the present invention may be include
as on reactable component a natural, synthetic or sequence-modified
(i.e., so-called "engineered") polypeptides (e.g., as disclosed
more fully in U.S. Pat. No. 6,018,030; U.S. Pat. No. 5,374,431;
U.S. Pat. No. 5,606,019 or U.S. Pat. No. 5,817,303, incorporated
fully by reference herein). Thus, although many of the following
examples employ albumin, it will be understood by those in this art
that other reactable components may be employed satisfactorily.
Reactable synthetic polymeric components, namely, those which
contain functional groups to cause cross-linking (e.g.
polyethylene-glycol polymers derivatized with electrophilic and
nucleophilic groups such as amine, succinimidyl, anhydride, thiol)
may also be employed in the practice of the present invention. See
in this regard, U.S. Pat. No. 6,166,130; U.S. Pat. No. 6,051,648;
or U.S. Pat. No. 5,900,245, the entirety of each being expressly
incorporated hereinto by reference.
[0026] Nominal compressive mechanical properties that are obtained
are similar to those of vertebral discs and lumbar vertebra. The
compressive properties of the described biomaterial 10-2 are very
different from highly rigid materials traditionally used as
implantable structural elements such as stainless steel, titanium,
polyacrylate bone cements, ceramics or carbon fiber composites, and
hence allow for better biomechanical compatibility in selected
indications. For example, the bioprosthetic vertebral discs of the
present invention exhibit flexibility comparable to the
biologically natural vertebral disc. More specifically, the
bioprosthetic vertebral discs of the present invention exhibit
flexibility comparable to the biologically natural vertebral disc
after being subjected to at least about 5 million cycles of a
cyclic load of about 0.85 MPa
[0027] The particular properties of the biopolymer 10-2 can be
"engineered" to suit specific end uses. For example, the biopolymer
may include fibrous or particulate reinforcement ("filler")
material, provided it is biocompatible.
[0028] Thus, natural or synthetic fibers, such as polyesters,
nylons, polyolefins, glass and the like of virtually any desired
denier may be employed. Furthermore, the reinforcing fibers may be
used in the form of a continuous length of single fibers (i.e.,
monofilaments) or a yarn, roving or rope of multiple filaments.
Moreover, the reinforcing media may be in the form of staple fibers
of predetermined lengths which are spun into yarns, rovings and/or
ropes of desired denier and continuous length. The mono- or
multifilamentary reinforcing materials may also be in the form of
woven or non-woven fabric structures. Suffice it to say here, that
virtually any physical form of fibrous reinforcing material may be
satisfactorily employed in the practice of the present
invention.
[0029] The reinforcing material may also be in the form of
particulates, such as synthetic or natural organic and inorganic
particulate reinforcement materials. Some representative examples
of such particulates include calcium carbonate, calcium phosphate,
hydroxyapatite bone chips, ceramic particles and the like.
[0030] The present invention will be further described with
reference to the following non-limiting Examples.
EXAMPLES
Example 1
[0031] A formulation formed of a protein solution (serum albumin)
and a cross linker (gluteraldehyde) was contained in the separate
chambers of a delivery device. When the device is triggered, the
two components are expelled from their respective chambers into a
mixing tip that combines the two solutions and mixes them as they
travel over the static mixing elements present in the tip. A
medical needle was attached to the mixing tip and the formulation
injected into the distal space between the vertebra of an explanted
pig spine. The tip can be attached to a needle, catheter, or other
hollow tubular device for delivery, for example. After 30 seconds,
the needle was withdrawn from the injection site. The material that
was injected had polymerized in place and did not exude out of the
needle hole. After 2 minutes, the disc-vertebra plate was dissected
and the presence of the biomaterial seen.
Example 2
[0032] Bovine calf spines were obtained from a commercial
slaughterhouse and cleaned by blunt and sharp dissection to expose
the vertebral bodies and the discs. A 4 mm hole was made into the
anterior face of the disc and the drill bit allowed to enter to the
center of the nucleus. The nuclear material was removed using
surgical forceps and curettes. The hollow space was filled with the
formulation described in Example 1. The material that was injected
polymerized in place and did not exude out of the hole. After 2
minutes the disc-vertebra plate was dissected and the presence of
the biomaterial seen.
Example 3
[0033] Bovine calf spines were obtained from a commercial
slaughterhouse and cleaned by blunt and sharp dissection to expose
the vertebral bodies and the discs. The top and bottom of the
vertebral bodies were cut parallel to each other at mid-height
using a miter box to yield a bone/disc/bone motion segment. A 4 mm
hole was made into the anterior face of the disc and the drill bit
allowed to enter into the center of the nucleus. The nuclear
material was removed using surgical forceps and curettes. The
hollow space was filled with the formulation described in Example
1. The material that was injected had polymerized in place and did
not exude out of the hole.
[0034] Once polymerization had occurred, the construct could be
compressed by hand in the front-back and left-right axes,
indicating flexibility was retained after repair of this segment.
Then, the construct was placed in a biomaterials testing device
(Instron electromechanical test station) and compressed repeatedly
to a load of 700 N to condition the construct. Thereafter, a
constant load of 700 N was applied to measure compressive creep.
The load was held for 10 min. During this time, the polymerized
material did not exit from the distal space or the hole. A force of
700 N is the published literature value for the load a lumbar
spinal disc experiences when a person of average built is standing
upright. The experiment was repeated on 5 separate samples.
[0035] In this example, the motion segment height was measured
before removal of the nucleus, after removal of the nucleus, after
filling with the biomaterial, and after loading and releasing the
load. It was found that (1) the removal of the nucleus reduced the
overall height of the material, as well as the compressibility, (2)
the filling with the biomaterial restored the disc height and the
compressibility.
Example 4
[0036] A disc of biomaterial formed by injecting a volume of
material with the formulation described in Example 1 into a cavity
mold was compressed for 100 and 1000 cycles at a compression rate
of 100 mm/min between a minimum stress of 200 kPa and a maximum
stress of either 470 or 800 kPa (equivalent to a normal lumbar
disc, cross sectional area of 1500 mm.sup.2, loaded between 300 N
and 700 or 1200 N). The disc element did not exhibit fracture,
permanent deformation, or demonstrate a loss of hydration (by mass
loss analysis). A force of 1200 N is the published literature value
for the compressive load a lumbar spinal disc experiences when a
person of average built flexes forward.
Example 5
[0037] Bovine calf spines were obtained and prepared as described
in Example 3. In this example, the nucleus pulposus was accessed
either from an anterior or a posterolateral direction. The
constructs were then placed under a cyclic load of 0.85 MPa at 5 Hz
and the load applied for >5 million cycles. During this time,
the constructs were kept in physiological saline solution
containing a non-fixative biocidal agent. At the end of the test
period, the constructs were removed and the disc sliced parallel to
the end plates to observe the status of the implants. The implant
present in the cavity created by the removal of the nucleus
pulposus, was intact and flexible.
Example 6
[0038] Samples of the biomaterial were formed as described in
Example 4. The biomaterial was then placed under a cyclic load of
0.5 MPa at approximately 2 Hz and the load applied for either >5
million cycles or >10 million cycles. During this time, the
constructs were kept in physiological saline solution containing a
non-fixative biocidal agent. The test samples remained intact
throughout the duration of the test, and demonstrated <10% loss
in original height.
[0039] While the invention has been described in connection with
what is presently considered to be the most practical and preferred
embodiment, it is to be understood that the invention is not to be
limited to the disclosed embodiment, but on the contrary, is
intended to cover various modifications and equivalent arrangements
included within the spirit and scope of the appended claims.
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