U.S. patent application number 10/195334 was filed with the patent office on 2003-02-13 for cartilage repair and regeneration scaffold and method.
Invention is credited to Malaviya, Prasanna, Plouhar, Pamela Lynn, Schwartz, Herbert Eugene.
Application Number | 20030033021 10/195334 |
Document ID | / |
Family ID | 26974786 |
Filed Date | 2003-02-13 |
United States Patent
Application |
20030033021 |
Kind Code |
A1 |
Plouhar, Pamela Lynn ; et
al. |
February 13, 2003 |
Cartilage repair and regeneration scaffold and method
Abstract
A method for the repair of a cartilaginous tissue defect, a
cartilage repair device and a method of making a cartilage repair
device are disclosed. In the method for the repair of a
cartilaginous tissue defect, a device comprising a synthetic
polymer is implanted into the defect, and a biological lubricant is
administered to the defect. The device comprises a synthetic
polymer and a biological lubricant.
Inventors: |
Plouhar, Pamela Lynn; (South
Bend, IN) ; Schwartz, Herbert Eugene; (Ft. Wayne,
IN) ; Malaviya, Prasanna; (Ft. Wayne, IN) |
Correspondence
Address: |
BARNES & THORNBURG
11 SOUTH MERIDIAN
INDIANAPOLIS
IN
46204
|
Family ID: |
26974786 |
Appl. No.: |
10/195334 |
Filed: |
July 15, 2002 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
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60388724 |
Jun 14, 2002 |
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60305786 |
Jul 16, 2001 |
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Current U.S.
Class: |
623/23.57 ;
424/423; 623/23.63 |
Current CPC
Class: |
A61F 2/30749 20130101;
A61F 2210/0004 20130101; A61L 27/18 20130101; A61B 17/0642
20130101; A61L 27/3633 20130101; A61P 19/00 20180101; A61B
2017/06057 20130101; A61F 2/0811 20130101; A61F 2002/30971
20130101; A61L 27/3604 20130101; A61F 2002/30294 20130101; A61F
2230/0091 20130101; A61F 2/0063 20130101; A61F 2/3872 20130101;
A61F 2002/30845 20130101; A61F 2230/0082 20130101; A61F 2002/30751
20130101; A61F 2002/30878 20130101; A61F 2230/0013 20130101; A61L
27/56 20130101; A61B 2017/00004 20130101; A61B 17/064 20130101;
A61B 2017/0641 20130101; A61B 2017/0646 20130101; A61B 2017/0475
20130101; A61F 2002/30233 20130101; A61F 2002/30293 20130101; A61F
2/30756 20130101; A61F 2/28 20130101; A61F 2002/30217 20130101;
A61F 2002/30841 20130101; A61F 2250/003 20130101; A61B 17/06166
20130101; A61F 2310/00365 20130101; A61L 2430/06 20130101; A61F
2002/2817 20130101; A61L 27/3654 20130101; A61F 2002/30153
20130101; A61F 2002/30261 20130101; A61F 2002/30975 20130101; A61F
2230/0086 20130101; A61F 2230/0063 20130101; A61B 17/0401 20130101;
A61F 2002/30281 20130101; A61F 2002/3021 20130101; C08L 67/04
20130101; A61F 2230/0069 20130101; A61F 2002/30429 20130101; A61F
2002/2839 20130101; A61F 2002/30766 20130101; A61L 27/18 20130101;
A61F 2002/30677 20130101; A61F 2002/30062 20130101; A61F 2220/0025
20130101; A61F 2002/30957 20130101; A61F 2230/0019 20130101; A61F
2250/0063 20130101; A61F 2002/30891 20130101; A61F 2/30965
20130101; A61F 2240/001 20130101; A61F 2240/004 20130101; A61F
2/3094 20130101; A61F 2/08 20130101; A61L 31/005 20130101; A61L
27/3852 20130101; A61F 2002/30131 20130101; A61F 2002/30032
20130101; A61F 2002/30225 20130101; A61F 2002/30764 20130101; A61F
2002/3096 20130101; A61F 2250/0067 20130101; A61F 2002/30604
20130101; A61F 2002/30199 20130101; A61F 2002/30785 20130101; A61F
2230/0067 20130101; A61F 2002/30892 20130101; A61L 27/3683
20130101; A61F 2002/30224 20130101; A61B 2017/0647 20130101; A61F
2002/30914 20130101; A61F 2/442 20130101 |
Class at
Publication: |
623/23.57 ;
623/23.63; 424/423 |
International
Class: |
A61F 002/28 |
Claims
1. A method for the repair of a cartilagenous tissue defect
comprising the steps of implanting a scaffold into the defect, and
administering a biological lubricant to the defect, wherein the
biological lubricant is not crosslinked to the scaffold.
2. The method of claim 1, wherein the implanting step and
administering step take place during a single surgical
procedure.
3. The method of claim 2, further comprising an additional
post-operative administration of biological lubricant to the
defect.
4. The method of claim 1, wherein the biological lubricant
comprises a GAG.
5. The method of claim 1, wherein the biological lubricant is
selected from the group consisting of: hyaluronic acid; a salt of
hyaluronic acid; sodium hyaluronate; dermatan sulfate; heparan
sulfate; chondroiton sulfate; keratan sulfate; synovial fluid; a
component of synovial fluid; vitronectin; and rooster comb
hyaluronate.
6. The method of claim 1, further comprising the step of closing an
incision site created to implant the scaffold, and wherein the
administering step is subsequent to the closing step, and the
biological lubricant is administered to the defect via injection in
the area of the defect.
7. The method of claim 1, wherein the defect is in the knee and the
biological lubricant is administered by injection into the knee
joint cavity.
8. The method of claim 1, wherein the biological lubricant is
administered to the defect by saturating the scaffold with a
biological lubricant solution prior to implantation.
9. The method of claim 1, wherein the scaffold is provided pre
saturated with biological lubricant
10. The method of claim 2, further comprising the step of providing
a series of additional biological lubricant injections to the area
of the defect subsequent to the surgical procedure.
11. The method of claim 10, wherein the defect is in the knee joint
and the injections are into the knee joint cavity.
12. The method of claim 10, wherein the series of additional
biological lubricant injections comprises a first additional
biological lubricant injection two weeks subsequent to the surgical
procedure and a second additional biological lubricant injection
four weeks subsequent to the surgical procedure.
13. The method of claim 1, wherein the defect is in a meniscus and
implanting step is a surgical procedure comprising performing a
partial menisectomy to create a space, placing the scaffold into
the space, and fixing the scaffold to surrounding meniscal
tissue.
14. The method of claim 1, wherein the scaffold comprises a
synthetic polymer.
15. The method of claim 14, wherein the synthetic polymer has a
structure selected from the group consisting of woven, knitted,
warped knitted, nonwoven, braided, and foamed.
16. The method of claim 14, wherein the synthetic polymer is
selected from the group consisting of PLA, PGA, PCL, PDO, TMC, PVA,
copolymers thereof, and blends thereof.
17. The method of claim 14, wherein the scaffold further comprises
an extracellular matrix.
18. The method of claim 1, wherein the device further comprises at
least one additional substance selected from the group consisting
of: a bioactive agent; a biologically derived substance; cells; and
a biocompatible inorganic material.
19. A method for the repair of a cartilaginous tissue defect
comprising the steps of implanting a scaffold comprising a
synthetic polymer into the defect, and administering a GAG to the
defect, wherein the GAG is not crosslinked to the scaffold.
20. The method of claim 19, wherein the GAG is not crosslinked to
the scaffold.
21. The method of claim 20, wherein the implanting step and
administering step take place during a single surgical
procedure.
22. The method of claim 21, further comprising an additional
post-operative administration of a biological lubricant to the
defect.
23. The method of claim 22, wherein the biological lubricant of the
additional post-operative administration comprises the GAG.
24. The method of claim 23, wherein the GAG comprises HA.
25. The method of claim 20, further comprising the step of closing
an incision site created to implant the scaffold, and wherein the
administering step is subsequent to the closing step, and the GAG
is administered to the defect via injection in the area of the
defect.
26. The method of claim 25, wherein the defect is in the knee and
the injection is into the knee joint cavity.
27. The method of claim 20, wherein the biological lubricant is
administered to the defect by saturating the scaffold with a
biological lubricant solution prior to implantation.
28. The method of claim 20, wherein the scaffold is provided
pre-saturated with biological lubricant.
29. The method of claim 19, further comprising a series of
post-operative biological lubricant injections wherein the series
of post-operative biological lubricant injections comprises a first
post-operative lubricant injection two weeks subsequent to the
surgical procedure and a second post-operative biological lubricant
injection four weeks subsequent to the surgical procedure.
30. The method of claim 19, wherein the defect is in a meniscus and
implanting step comprises performing a partial menisectomy to
create a space, placing the scaffold into the space, and fixing the
scaffold to surrounding meniscal tissue.
31. The method of claim 19, wherein the GAG is HA.
32. The method of claim 19, wherein the GAG is crosslinked to the
scaffold.
33. The method of claim 19, wherein the scaffold consists
essentially of the synthetic polymer.
34. A cartilage repair device comprising a synthetic polymer
scaffold and a biological lubricant applied to the polymer.
35. The cartilage repair device of claim 34, wherein the biological
lubricant comprises a solution.
36. The cartilage repair device of claim 34, wherein the biological
lubricant solution comprises a GAG.
37. The cartilage repair device of claim 36, wherein the biological
lubricant solution comprises HA.
38. The cartilage repair device of claim 37, wherein the HA is a
high molecular weight sodium hyaluronate.
39. The cartilage repair device of claim 34, wherein the device
further comprises a biologic component.
40. The cartilage repair device of claim 39, wherein the biologic
component comprises an ECM.
41. The cartilage repair device of claim 40, wherein the ECM matrix
comprises tissue derived from a source selected from the group
consisting of: vertebrate small intestine submucosa; vertebrate
liver basement membrane; vertebrate bladder submucosa; vertebrate
stomach submucosa; vertebrate alimentary tissue; vertebrate
respiratory tissue; and vertebrate genital tissue.
42. The cartilage repair device of claim 34, further comprising an
additional material selected from the group consisting of: a
bioactive agent; a biologically derived substance; and cells.
43. The cartilage repair device of claim 34 wherein the synthetic
polymer scaffold comprises a plug configured to be positioned in an
opening formed in damaged cartilage.
44. The cartilage repair device of claim 43 wherein the plug is
secured to an anchor.
45. The cartilage repair device of claim 43 further comprising an
anchor configured to secure the plug in the opening.
46. A method of making a cartilage repair device comprising:
providing a scaffold; providing a biological lubricant in liquid
form; and wetting the scaffold with the liquid biological lubricant
to form a wet implant.
47. The method of claim 46, further comprising packaging the wet
implant and terminally sterilizing the packaged wet implant.
48. The method of claim 46, further comprising drying the wet
implant, packaging the dry implant and terminally sterilizing the
packaged dry implant.
49. The method of claim 46, wherein the scaffold comprises a
synthetic polymer.
50. The method of claim 49, wherein the scaffold further comprises
a naturally occurring extracellular matrix.
51. The method of claim 46, further comprising incorporating into
the wet implant a material selected from the group consisting of: a
bioactive agent; a biologically derived substance; and cells.
Description
[0001] This application claims priority to U.S. Provisional
Application No. 60/388,724, filed Jun. 14, 2002, and U.S.
Provisional Application No. 60/305,786, filed Jul. 16, 2001, hereby
incorporated by reference.
CROSS REFERENCE
[0002] Cross reference is made to copending U.S. patent
applications Ser. No. ______ entitled "Meniscus Regeneration Device
and Method" (Attorney Docket No. 265280-71141, DEP-745); Ser. No.
______ entitled "Devices from Naturally Occurring Biologically
Derived Materials" (Attorney Docket No. 265280-71142, DEP-748);
Ser. No. ______ entitled "Cartilage Repair Apparatus and Method"
(Attorney Docket No. 265280-71143, DEP-749); Ser. No. ______
entitled "Unitary Surgical Device and Method" (Attorney Docket No.
DEP-750); Ser. No. ______ entitled "Hybrid Biologic/Synthetic
Porous Extracellular Matrix Scaffolds" (Attorney Docket No.
265280-71144, DEP-751); Ser. No. ______ entitled "Cartilage Repair
and Regeneration Device and Method" (Attorney Docket No.
265280-71145, DEP-752); Ser. No. ______ entitled "Porous
Extracellular Matrix Scaffold and Method" (Attorney Docket No.
265280-71146, DEP-747); and Ser. No. ______ entitled "Porous
Delivery Scaffold and Method" (Attorney Docket No. 265280-71207,
DEP-762), each of which is assigned to the same assignee as the
present application, each of which is filed concurrently herewith,
and each of which is hereby incorporated by reference. Cross
reference is also made to U.S. patent application Ser. No.
10/172,347 entitled "Hybrid Biologic-Synthetic Bioabsorbable
Scaffolds" which was filed on Jun. 14, 2002, which is assigned to
the same assignee as the present application, and which is hereby
incorporated by reference.
BACKGROUND OF THE INVENTION
[0003] Articular cartilage is a type of hyaline cartilage that
lines the surfaces of the opposing bones in a diarthrodial joint
(e.g. knee, hip, shoulder, etc.). Articular cartilage provides a
near-frictionless articulation between the bones, while also
functioning to absorb and transmit the compressive and shear forces
encountered in the joint. Further, since the tissue associated with
articular cartilage is aneural, these load absorbing and
transmitting functions occur in a painless fashion in a healthy
joint.
[0004] Fibrocartilage is found in diarthrodial joints, symphyseal
joints, intervertebral discs, articular discs, as inclusions in
certain tendons that wrap around a pulley, and at insertion sites
of ligaments and tendons into bone. Made of a mixture of collagen
type I and type II fibers, fibrocartilage can also be damaged,
causing pain in the affected joint. It is understood for purposes
of this application that the term "cartilage" includes articular
cartilage and fibrocartilage.
[0005] When cartilage tissue is no longer healthy it can cause
debilitating pain in the joint. For example, articular cartilage
health can be affected by disease, aging, or trauma, all of which
primarily involve a breakdown of the matrix consisting of a dense
network of proteoglycan aggregates, collagen fibers, and other
smaller matrix proteins. Tissue cells are unable to induce an
adequate healing response because they are unable to migrate, being
enclosed in lacunae surrounded by a dense matrix. Further, since
the tissue is avascular, initiation of healing by circulating cells
is limited. Similarly, damage or degeneration of knee
fibrocartilage i.e. the menisci, is a common occurrence. A damaged
or degenerated meniscus has little ability to heal or repair itself
because the pathology frequently occurs in the avascular part of
the tissue.
[0006] Several articular cartilage repair strategies have been
attempted in the past. These include surgical techniques such as
microfracturing or performing abrasion arthroplasty on the bone bed
to gain vascular access, and hence, stimulate extrinsic repair in
the defective region. The long-term outcome of these techniques,
however, has been known to result in mechanically inferior
fibrocartilagenous tissue.
[0007] Another surgical technique is mosaicplasty or osteochondral
autograft transfer system (OATS). In this case, cylindrical plugs
of healthy articular cartilage from a low-load bearing region of
the knee are taken and transplanted into the defective region. This
technique, however, can result in excessive donor-site morbidity
and associated pain. Additionally, surgeons have reported that the
gaps between the round transplants are frequently filled with
fibrocartilage which can eventually erode away, thus potentially
compromising the integrity of repair throughout the affected
area.
[0008] The only FDA-approved cartilage treatment product in the
market involves autologous chondrocyte implantation (CartiCel.TM.).
Autologous chondrocyte implantation involves performing an initial
biopsy of healthy cartilage from the patient, isolating the cells
from the tissue, expanding the cells in vitro by passaging them in
culture, and then reintroducing the cells into the defective area.
The cells are retained within the defect by applying a periosteal
tissue patch over the defect, suturing the edges of the patch to
the host tissue, and then sealing with fibrin glue. The efficacy of
this expensive procedure, however, has recently been put into
question by studies that have shown that only a few of the injected
cells are retained within the defect and that they may not
significantly contribute to the repair process. The healing
observed is similar to that observed with microfracture or abrasion
of the bone bed, suggesting that it is the preparation of the bone
bed and not the introduction of the cells that facilitates the
healing process.
[0009] Tissue engineering strategies for healing cartilage are
being investigated by several academic and commercial teams and
show some promise. One approach primarily involves using a
biocompatible biologic or synthetic scaffold to deliver cells or
stimulants to the defect site. The scaffold material can be a
purified biologic polymer in the form of a porous scaffold or a gel
(purified collagens, glycoproteins, proteoglycans, polysaccharides,
or the like in various combinations) or porous scaffolds of
synthetic biodegradable polymers (PLA, PGA, PDS, PCL, or the like,
in various combinations). Several challenges remain with this
approach, however. Some of these challenges include retention of
the active stimulant at the defect site, inability to control the
rate of release of the stimulant (resulting in tissue necrosis due
to overdose), and cytotoxicity of the cells due to the degradation
by-products of the synthetic polymers.
[0010] In another technique, various collagen scaffolds have been
used to provide a scaffold for repair and regeneration of damaged
cartilage tissue. U.S. Pat. No. 6,042,610 to ReGen Biologics,
hereby incorporated by reference, discloses the use of a device to
regenerate meniscal fibrocartilage. The disclosed device comprises
a bioabsorbable material made at least in part from purified
collagen and glycosaminoglycans (GAG). Purified collagen and
glycosaminoglycans are co-lyophilized to create a foam and then
cross-linked to form the device. The device can be used to provide
augmentation for a damaged meniscus. Related U.S. Pat. Nos.
5,735,903, 5,479,033, 5,306,311, 5,007,934, and 4,880,429 also
disclose a meniscal augmentation device for establishing a scaffold
adapted for ingrowth of meniscal fibrochondrocyts.
[0011] It is also known to use naturally occurring extracellular
matrices (ECMs) to provide a scaffold for tissue repair and
regeneration. One such ECM is small intestine submucosa (SIS). SIS
has been described as a natural biomaterial used to repair,
support, and stabilize a wide variety of anatomical defects and
traumatic injuries. See, for example, Cook.RTM. Online New Release
provided by Cook Biotech at "www.cookgroup.com". The SIS material
is reported to be a naturally-occurring collagenous matrix derived
from porcine small intestinal submucosa that models the qualities
of its host when implanted in human soft tissues. Further, it is
taught that the SIS material provides a natural matrix with a
three-dimensional structure and biochemical composition that
attracts host cells and supports tissue remodeling. SIS products,
such as Oasis material and Surgisis material, are commercially
available from Cook Biotech, Bloomington, Ind.
[0012] An SIS product referred to as RESTORE Orthobiologic Implant
is available from DePuy Orthopaedics, Inc. in Warsaw, Ind. The
DePuy product is described for use during rotator cuff surgery, and
is provided as a resorbable framework that allows the rotator cuff
tendon to regenerate itself. The RESTORE Implant is derived from
porcine small intestine submucosa that has been cleaned,
disinfected, and sterilized. Small intestine submucosa (SIS) has
been described as a naturally-occurring ECM composed primarily of
collagenous proteins. Other biological molecules, such as growth
factors, glycosaminoglycans, etc., have also been identified in
SIS. See Hodde et al., Tissue Eng. 2(3): 209-217 (1996);
Voytik-Harbin et al., J. Cell Biochem., 67:478-491 (1997);
McPherson and Badylak, Tissue Eng., 4(1): 75-83 (1998); Hodde et
al., Endothelium, 8(1):11-24 (2001); Hodde and Hiles, Wounds,
13(5): 195-201 (2001); Hurst and Bonner, J. Biomater. Sci. Polym.
Ed., 12(11) 1267-1279 (2001); Hodde et al., Biomaterial, 23(8):
1841-1848 (2002); and Hodde, Tissue Eng., 8(2): 295-308 (2002), all
of which are incorporated by reference herein. During seven years
of preclinical testing in animals, there were no incidences of
infection transmission form the implant to the host, and the
RESTORE Implant has not decreased the systemic activity of the
immune system. See Allman et al., Transplant, 17(11): 1631-1640
(2001); Allman et al., Tissue Eng., 8(1): 53-62 (2002).
[0013] While small intestine submucosa is available, other sources
of submucosa are known to be effective for tissue remodeling. These
sources include, but are not limited to, stomach, bladder,
alimentary, respiratory, or genital submucosa, or liver basement
membrane. See, e.g., U.S. Pat. Nos. 6,171,344, 6,099,567, and
5,554,389, hereby incorporated by reference. Further, while SIS is
most often porcine derived, it is known that these various
submucosa materials may be derived from non-porcine sources,
including bovine and ovine sources. Additionally, other collagenous
matrices are known, for example lamina propria and stratum
compactum.
[0014] It is also known to promote cartilage growth using
glycosaminoglycans (GAG), such as hyaluronic acid (HA), dermatan
sulfate, heparan sulfate, chondroiton sulfates, keratin sulfate,
etc. See, e.g., U.S. Pat. Nos. 6,251,876 and 6,288,043, hereby
incorporated by reference. GAGs are naturally found mostly in the
extracellular matrix and on the cell surface as proteoglycans.
These macromolecules are secreted by cells and play a role in both
signal transduction and storage of some growth factors. In addition
to the biological functions, the viscoelastic properties of GAGs
provide a mechanical function by providing lubrication within a
joint, to decrease friction. Hyaluronic acid is a natural component
of the extracellular matrix of most cartilage tissues. HA is a
linear polymer made up of repeating GAG disaccharide units of
D-glucuronic acid and N-acetylglycosamine in .beta.(1-3) and
.beta.(1-4) linkages. Illustratively HA can have a molecular weight
ranging from about 300,000 kDa to about 6,000,000 kDa and can be
uncrosslinked, naturally crosslinked, or crosslinked using
mechanical, chemical, or enzymatic methods. The effect of treating
extrasynovial tendons with HA and chemically modified HA has also
been studied with reference to tendon gliding resistance and tendon
adhesions to surrounding tissue after repair. Momose, Amadio, Sun,
Chunfeng Zhao, Zobitz, Harrington and An, "Surface Modification of
Extrasynovial Tendon by Chemically Modified Hyaluronic Acid
Coating," J. Biomed. Mater. Res. 59: 219-224 (2002).
SUMMARY OF THE INVENTION
[0015] It has been found that the combination of a biocompatible
scaffold and HA produces a synergistic effect. Healing rates and/or
quality of healing is better than the healing expected from
additive effects of the scaffold or HA alone. Moreover, it has been
found that retention of HA at the defect site is not problematic
and co-administration of the scaffold and HA does not require HA to
be cross-linked to the scaffold material. Thus, the present
invention provides methods for the repair of damaged or diseased
cartilaginous tissue, wherein a biocompatible scaffold and HA are
co-administered to the cartilaginous tissue defect.
[0016] In addition to HA, GAGs such as dermatan sulfate, heparan
sulfate, chondroitin sulfate, and keratan sulfate are also expected
to be usable with the present invention. As used herein,
"biological lubricant" is used to identify the aforementioned
materials and others such as synovial fluid and components thereof,
including mucinous glycoproteins (for example lubricin),
tribonectins, articular cartilage superficial zone proteins,
surface-active phospholipids, and lubricating glycoproteins I, II;
vitronectin; and rooster comb hyaluronate (e.g. commercially
available HEALON.RTM., (Pharmacia Corporation, Peapack, N.J.), for
example, and mixtures thereof. Such materials serve both a
biological and a mechanical function: they play a biological role
in directly and indirectly influencing cellular behavior by being
involved in signal transduction alone or in conjunction with other
extracellular matrix components such as growth factors,
glycoproteins, collagens etc., and a mechanical role in providing
lubrication. Thus, the use of the expression "biological lubricant"
is intended to encompass materials that provide some biological
function (influencing cellular behavior) and some mechanical
function (lubrication).
[0017] It is believed that some commercially-available biological
lubricants can be used in the practice of the present invention.
Examples of such commercially-available lubricants include:
ARTHREASE.TM. high molecular weight sodium hyaluronate, available
in Europe from DePuy Orthopaedics, Inc. of Warsaw, Ind.;
SYNVISC.RTM. Hylan G-F 20, manufactured by Biomatrix, Inc., of
Ridgefield, N.J. and distributed by Wyeth-Ayerst Pharmaceuticals of
Philadelphia, Pa.; and HYLAGAN.RTM. sodium hyaluronate, available
from Sanofi-Synthelabo, Inc., of New York, N.Y. The expressions
"HA", "GAG", and "biological lubricant" are intended to encompass
these materials. It should be understood that there may be other
salts of hyaluronic acid that may be used in the present invention,
and the expressions "HA", "GAG", and "biological lubricant" should
be understood to encompass such salts.
[0018] The three-dimensional biologic or synthetic scaffolds may be
provided in the form of a fibrous nonwoven or foam material. The
scaffold preferably has interconnecting pores or voids to
facilitate the transport of nutrients and/or invasion of cells into
the scaffold. The interconnected voids range in size, for example,
from about 20 to 400 microns, illustratively 50 to 250 microns,
depending on the application. The range of the void size in the
construct can be manipulated by changing process steps during
construct fabrication. See Ser. No. ______ entitled "Porous
Delivery Scaffold and Method" (Attorney Docket No. 265280-71207,
DEP-762), already incorporated by reference. The foam optionally
may be formed around a reinforcing material, for example, a knitted
mesh or an ECM layer. See U.S. patent application Ser. No.
10/172,347 entitled "Hybrid Biologic-Synthetic Bioabsorbable
Scaffolds" which was filed on Jun. 14, 2002, already incorporated
by reference. The fibers used to make the scaffold can be made of
any biocompatible material, including bioabsorbable materials such
as polylactic acid (PLA), polyglycolic acid (PGA), polycaprolactone
(PCL), polydioxanone (PDO), trimethylene carbonate (TMC), polyvinyl
alcohol (PVA), copolymers or blends thereof, or combinations of
synthetic and biologic polymers. See also, Ser. No. ______ entitled
"Hybrid Biologic/Synthetic Porous Extracellular Matrix Scaffolds"
(Attorney Docket No. 265280-71144, DEP-751). The biologic polymers
may comprise ECM, particularly comminuted ECM. In an exemplary
embodiment, the fibers that comprise scaffold are formed of a
polylactic acid and polyglycolic acid copolymer at a 95:5 mole
ratio.
[0019] In one embodiment of the present invention, a method is
provided wherein the scaffold material is implanted into the
defect. The biological lubricant, which can be a GAG or HA for
example, is administered separately, either at the time of surgery
or via injection subsequent to closure of the incision. Optionally,
a series of additional injections may be administered over a period
of time. In either case, the injection may be made
intra-articularly.
[0020] In another embodiment, a method is provided wherein the
scaffold material and the biological lubricant are administered to
the defect together. The scaffold material may be saturated with
the biological lubricant at the time of surgery. Alternatively, the
scaffold material may be saturated with the biological lubricant at
the time of manufacture, and may be packaged together. Optionally,
a series of additional injections may be administered in this
method as well.
[0021] In still another embodiment, an implantable device is
provided comprising a scaffold material saturated with a biological
lubricant.
BRIEF DESCRIPTION OF THE DRAWINGS
[0022] FIG. 1 is a diagrammatical view showing a tibial platform
with a typical meniscus structure on the platform and a portion of
the meniscus removed for illustration purposes, the tibia platform
being below the condyles of the femur;
[0023] FIG. 2 is a view looking down at the tibial platform and
showing diagrammatically the insertion of a scaffold to replace the
portion of the meniscus removed;
[0024] FIG. 3 shows the inserted scaffold in a position to be
attached to the portions of the meniscus remaining after the
injured portion is removed;
[0025] FIG. 4 is a sectional view taken from FIG. 3 along the lines
4-4;
[0026] FIG. 5 is a perspective view showing an open wedge-shaped
device comprising an upper panel and a lower panel angularly
separated to define an apex portion and a base portion;
[0027] FIG. 6 shows a wedge shaped device prior to folding with a
pocket shown in imaginary lines formed in the device;
[0028] FIG. 7 shows a further step in the process in making the
device shown in FIG. 6 to produce a filled, wedge-shaped
device;
[0029] FIG. 8 is a top view of a ECM device used for the repair of
a meniscal defect and having barbs for attachment;
[0030] FIG. 9 is a top view of a device similar to that shown in
FIG. 1, except having sutures for attachment;
[0031] FIG. 10 is a perspective, partially cut-away view of a
meniscus with the device of FIG. 1 inserted into the meniscus;
[0032] FIG. 11 is a cross sectional view of a cartilage repair
device implanted in subchondral bone, note that the anchor is shown
in elevation rather than cross section for clarity of description;
and
[0033] FIG. 12 is a cross sectional view of a cartilage repair
device which uses an alternative embodiment of an anchor.
DETAILED DESCRIPTION
[0034] While the invention is susceptible to various modifications
and alternative forms, specific embodiments thereof have been shown
by way of example in the drawings and will herein be described in
detail. It should be understood, however, that there is no intent
to limit the invention to the particular forms disclosed, but on
the contrary, the intention is to cover all modifications,
equivalents, and alternatives falling within the spirit and scope
of the invention as defined by the appended claims.
[0035] Referring to FIG. 1, it will be seen that a tibial platform
10 below the condyles 12 of a knee support a meniscus 11 from which
an illustrative defective portion 14 is removed to leave a
wedge-shaped space 16. In the removal process, the surgeon will
often leave an outer rim 18 of the meniscus. The meniscus provides
a large surface of articulation between the otherwise incongruent
surfaces of the tibia platform or plateau and the femur condyles
(such indicated at 12). The meniscus serves to reduce contact
stresses and wear in the knee joint.
[0036] The portion 14 removed from the structure shown in FIG. 1
includes a portion of the original meniscus which was within the
avascular zone, particularly the radially inner portion, and may
include a portion of the original meniscus which was within the
vascular zone.
[0037] FIG. 2 shows how a scaffold device 20 may illustratively be
inserted into the space 16 to be against the outer rim 18. This
illustrative scaffold 20 is shown in FIGS. 3 and 4 in position
filling the space 16 and against the rim 18 left by the surgeon.
FIG. 4 shows the scaffold as comprising an upper cover or upper
panel 22 and a lower cover or lower panel 24. These panels 22, 24,
which may illustratively be angularly related, will define an
internal space 26 between the covers. Internal space 26 optionally
may be filled with a biological material, a biological structure,
or a synthetic structure providing a framework for regeneration of
the meniscus into the space 16. Illustratively, panels 22, 24 may
be made from woven or nonwoven mats of synthetic polymer or
synthetic/biologic polymers. Alternatively, scaffold 20 may be
constructed by forming the synthetic or synthetic/biologic polymers
in a mold, or by sculpting a block of the polymer into the proper
shape.
[0038] The scaffolds may comprise synthetic polymers such as
polylactic acid (PLA), polyglocolic acid (PGA), polycaprolactone
(PCL), polydioxanone (PDO), trimethylene carbonate (TMC), polyvinyl
alcohol (PVA), and copolymers and blends thereof. The synthetic
polymers may be provided as textiles with woven, knitted, warped
knitted, nonwoven, braided, and foamed structures, and
illustratively may be imbedded in ECM material, as in copending
U.S. patent application Ser. No. 10/172,347 entitled "Hybrid
Biologic-Synthetic Bioabsorbable Scaffolds" which was filed on Jun.
14, 2002, or may be provided as foams with or without ECM
materials, as in copending U.S. patent application Ser. No. ______
entitled "Hybrid Biologic/Synthetic Porous Extracellular Matrix
Scaffolds" (Attorney Docket No. 265280-71144, DEP-751). Thus, the
scaffold may be made of biocompatible polymers, with or without a
biologic component, and may be provided in a variety of woven,
knitted, nonwoven, braided formed, or molded, or other
configurations.
[0039] Scaffold 20 may be inserted, for example, in arthroscopic
surgery through portals provided in the outer anterior surface of
the knee opening into the knee cavity between the condyles 12 and
the tibial platform 10. However, any surgical procedure to insert a
device into damaged cartilage is within the scope of the present
invention. Illustratively, the upper cover 22 of the scaffold 20
may serve as a bearing surface for the condyle 12 disposed
thereabove and be subjected to the compression and stress forces
involved in articulation of the knee. The condyle will move upon
the upper surface of the cover 22.
[0040] Turning to FIGS. 5, 6 and 7, it will be seen that an
illustrative device is somewhat diagrammatically illustrated. The
illustrative device 30 includes an upper panel 32 and a lower panel
34 defining a wedge-shaped device having a base portion 36 and an
apex portion 38. FIG. 6 suggests that the device may include a
formed wedge-shaped cavity 39 (illustrated in phantom) and that the
device may be folded about a fold line 40 to provide a device such
as indicated at 42 in FIG. 7. While the FIG. 5 device 30 suggests
an open wedge-shaped design, the device 42 in FIG. 7 suggests that,
between the upper and lower panels 32, 34 a mass of biological
material may be disposed. In FIG. 6, a plurality of tacks 44 are
shown attached to one of the two panels of the device to be used
for securing the device to surrounding tissue in the knee. The
panels 32, 34 may be trimmed to the desired wedge shape.
[0041] Referring now to FIGS. 8-10, there are shown scaffolds
similar to those shown in FIGS. 6-7, except that device 100 need
not be wedge shaped. Scaffold 100 comprises panels 102 and 104,
with a pillow 106 of biological or synthetic material shaped to
fill the void in meniscus 111 left after a partial menisectomy, as
illustrated in FIG. 1. The pillow is placed between panels 102 and
104. In the illustrative embodiment, pillow 106 is smaller than
panels 102 and 104, and wing portions 105 of panels 102 and 104
extend beyond pillow 106.
[0042] As shown in FIG. 8, scaffold 100 may be provided with barbed
darts 112 extending from wings 105. A needle or similar device
would be used to push the barbed darts 112 into or through the
meniscus to secure scaffold 100 to the meniscus. Barbed darts may
be made of any biocompatible material sufficiently rigid to secure
scaffold 100 to the meniscus. Barbed darts 112 may be provided
integrally with scaffold 100 or may be added by the surgeon prior
to insertion of the device.
[0043] The scaffold 100 illustrated in FIG. 9 is similar to the
scaffold shown in FIG. 8, except that instead of barbed darts, the
scaffold of FIG. 9 is provided with sutures 113. The scaffold of
FIG. 9 may be affixed to the meniscus in a manner similar to that
of the scaffold of FIG. 8. A needle or similar device would be used
to push the sutures 113 through the meniscus. As illustrated in
FIG. 10, the sutures may be tied together on the outside of the
meniscus to form knots 120 that secure scaffold 100 in place.
[0044] While in the various embodiments discussed herein, tacks and
sutures have been shown for anchoring the devices, it will be
appreciated that the devices may be anchored by any other method at
the choice of the surgeon.
[0045] FIGS. 11 and 12 illustrate several scaffolds that can be
used in conjunction with a biological lubricant for cartilage
repair. Referring now to FIG. 11, a cartilage repair device 210 is
provided for repairing damaged or diseased cartilage. The device
210 includes an anchor 212 which is anchored or otherwise
positioned in an opening formed in both a section of native
cartilage 216 and the underlying subchondral bone 218. The anchor
212 is configured to be secured in an area from which damaged,
diseased, or destroyed native cartilage and possibly bone have been
removed. The anchor 212 includes an elongated central body portion
220 and a head portion 222. The body portion 220 extends downwardly
from a lower surface of the head portion 222. As shown in FIG. 11,
the body portion 220 may have a number of barbs 224 extending
therefrom for engaging the sidewalls of the opening formed in the
bone 218. In the illustrative embodiment described herein, the
barbs 224 extend radially outwardly and are inclined slightly
toward the head portion 222 of the anchor 212.
[0046] The cartilage repair device 210 also includes a plug 226.
The plug 226 is secured to the anchor 212. Specifically, the plug
226 is secured to the upper surface of the head portion 222 of the
anchor 212. The plug 226 allows for communication across the
removed portion (i.e., the portion of the native cartilage 216 from
which the damaged or diseased cartilage has been removed) and the
adjacent healthy cartilage. As such, the plug 226 functions as a
chondrogenic growth-supporting matrix for promoting a positive
cellular response in an effort to achieve articular cartilage
regeneration.
[0047] The anchor 212 of the cartilage repair device 210 may be
constructed of numerous types of synthetic or naturally occurring
materials. For example, the anchor 212 may be constructed with a
bioabsorbable polymer. Examples of such polymers include:
polyesters of [alpha]-hydroxycarboxylic acids, such as
poly(L-lactide) (PLLA), polyglycolide (PGA); poly-p-dioxanone
(PDS); polycaprolactone (PCL); and any other bioresorbable and
biocompatible polymer, co-polymer or mixture of polymers or
co-polymers that are commonly used in the construction of
prosthetic implants. Moreover, the anchor 212 may be constructed
with a naturally occurring material such as a naturally occurring
ECM (e.g., SIS). In such a case, the head portion 222 and body
portion 220 of the anchor 212 may be configured as monolithic
structures formed from naturally occurring ECM which is cured to be
rigid and hardened to facilitate attachment to the bone 218. As
such, it should be appreciated that the ECM material from which the
anchor 212 is fabricated is cured to produce a structure which
possesses the necessary hardness and toughness to allow the anchor
212 to be driven into bone tissue (i.e., the subchondral bone 218).
See U.S. patent application Ser. No. ______ entitled "Devices from
Naturally Occurring Biologically Derived Materials" (Attorney
Docket No. 265280-71142, DEP-748), already incorporated by
reference. It should be understood that the material selected for
the anchor 212 may also comprise mixtures or composites of
materials. For example, the anchor 212 could comprise both a
polymer and ECM material.
[0048] As mentioned above, the plug 226, which is fixed to the
anchor 212, functions as a chondrogenic growth-supporting matrix
for promoting vascular invasion and cellular proliferation in an
effort to achieve articular cartilage regeneration. A central body
230 of the plug 226 is configured as a porous structure of
biodegradable material. When anchored to a defective area of
cartilage, cells can migrate into and proliferate within the plug
226, biodegrade the plug 226 while, at the same time, synthesize
new and healthy tissue to heal the defective area. The plug 226 may
be made out of a nonwoven or foam scaffold of synthetic or
synthetic/biologic fibers with the desired porosity and material
density. Specifically, the material density and/or porosity of the
plug 226 may be varied to control cell migration and proliferation.
The cells can migrate from adjacent tissue or from synovial fluid.
The fibers from which the plug 226 is constructed also may be
formed to have a structural rigidity sufficient to withstand the
compression and shear stress to which the cartilage 216 is
subjected. As such, the porous material from which the plug 226 is
constructed should have the structural rigidity necessary to bear
the forces associated with the other bone.
[0049] One particularly useful material for fabricating the plug
226 is a porous scaffold or "foam" composed of synthetic fibers or
a combination of synthetic fibers and naturally occurring ECM. Both
the material density and the pore size of the foam plug 226 may be
varied to fit the needs of a given plug design. Such foams may be
fabricated by lyophilizing (i.e., freeze-drying) the fibers
suspended in water. The material density and pore size of the
resultant foam may be varied by controlling, among other things,
the rate of freezing of the fiber suspension and/or the amount of
water or moisture content in the fiber suspension at the on-set of
the freezing process. See U.S. patent application Ser. No. ______
entitled "Cartilage Repair Apparatus and Method" (Attorney Docket
265280-71143, DEP-7490 and Ser. No. ______ entitled "Porous
Extracellular Matrix Scaffold and Method" (Attorney Docket
265280-71146, DEP-747), already incorporated by reference.
[0050] Referring now to FIG. 12, there is shown another embodiment
of a cartilage repair device (hereinafter referred to with
reference numeral 410). The cartilage repair device 410 is somewhat
similar to the cartilage repair device 210. As such, the same
reference numerals are used in FIG. 12 to identify components which
have previously been discussed, with additional discussion thereof
being unwarranted. The cartilage repair device 410 includes an
anchor 412 which is used in lieu of the anchor 212 described in
regard to FIG. 11. In particular, in the embodiment shown in FIG.
12, the plug 226 is positioned in an osteochondral defect 414
without the use of a bottom-mounted anchor (i.e., the anchor 212 of
FIG. 11). Similarly to as described above, the plug 226 is
constructed out of synthetic fibers or a combination of synthetic
fibers and naturally occurring ECM (e.g., SIS) having a desired
porosity and material density.
[0051] The plug 226 is retained in the hole formed in the cartilage
216 and protected from in vivo forces by an annular shaped anchor
412. The anchor 412 may be provided in many different
configurations which allow it to be press fit or otherwise anchored
into the subchondral bone 218. For example, as shown in FIG. 12,
the anchor 412 may be "bottle cap"-shaped so as to allow the anchor
412 to be press fit or otherwise secured into an annular groove 416
formed in the subchondral bone 218. The groove may be formed and
the anchor may be shaped as described and shown in Patent
Cooperation Treaty publication WO 01/39694 A2, published Jun. 7,
2001 entitled "Fixation Technology", the complete disclosure of
which is incorporated by reference herein. Alternatively, the
anchor 412 may be mechanically secured to the subchondral bone 218
by use of adhesive or other types of anchoring structures (e.g.,
barbs).
[0052] The anchor 412 of the cartilage repair device 410 may be
constructed from numerous types of synthetic or naturally occurring
materials. For example, the anchor 212 may be constructed with a
bioabsorbable polymer such as PLLA, PGA, PDS, PCL, or any other
such bioabsorbable polymer which is commonly used in the
construction of prosthetic implants. Moreover, the anchor 412 may
be constructed from a naturally occurring material such as a
naturally occurring ECM (e.g., SIS) that is cured or otherwise
fabricated to be rigid and hardened to facilitate attachment to the
bone in the same manner as described above in regard to the anchor
212 and/or the plug 226 of FIG. 11.
[0053] It is expected that the teachings of the present invention
may also be advantageously combined with the teachings of the
following U.S. patent applications filed concurrently herewith and
which are incorporated by reference herein: Ser. No. ______
entitled "Devices from Naturally Occurring Biologically Derived
Materials" (Attorney Docket No. 265280-71142, DEP-748); Ser. No.
______ entitled "Unitary Surgical Device and Method" (Attorney
Docket No. DEP-750); and Ser. No. ______ entitled "Porous
Extracellular Matrix Scaffold and Method" (Attorney Docket No.
265280-71146, DEP-747). It is expected that the materials and
devices disclosed in those patent applications can be used in the
present invention.
[0054] Similarly, it is expected that other materials may be
combined with the biological lubricant or with the scaffold. For
example, bioactive agents, biologically-derived agents, cells,
biocompatible inorganic material and/or combinations thereof may be
mixed with the scaffold material or biological lubricant.
[0055] "Bioactive agents" include one or more of the following:
chemotactic agents; therapeutic agents (e.g. antibiotics, steroidal
and non-steroidal analgesics and anti-inflammatories,
anti-rejection agents such as immunosuppressants and anti-cancer
drugs); various proteins (e.g. short chain peptides, bone
morphogenic proteins, glycoprotein and lipoprotein); cell
attachment mediators; biologically active ligands; integrin binding
sequence; ligands; various growth and/or differentiation agents
(e.g. epidermal growth factor, IGF-I, IGF-II, TGF-.beta. I-III,
growth and differentiation factors, vascular endothelial growth
factors, fibroblast growth factors, platelet derived growth
factors, insulin derived growth factor and transforming growth
factors, parathyroid hormone, parathyroid hormone related peptide,
bFGF; TGF.beta. superfamily factors; BMP-2; BMP-4; BMP-6; BMP-12;
sonic hedgehog; GDF5; GDF6; GDF8; PDGF); small molecules that
affect the upregulation of specific growth factors; tenascin-C;
hyaluronic acid; chondroitin sulfate; fibronectin; decorin;
thromboelastin; thrombin-derived peptides; heparin-binding domains;
heparin; heparan sulfate; DNA fragments; and DNA plasmids. If other
such substances have therapeutic value in the orthopaedic field, it
is anticipated that at least some of these substances will have use
in the present invention, and such substances should be included in
the meaning of "bioactive agent" and "bioactive agents" unless
expressly limited otherwise.
[0056] "Biologically derived agents" include one or more of the
following: bone (autograft, allograft, and xenograft) and derivates
of bone; cartilage (autograft, allograft, and xenograft),
including, for example, meniscal tissue, and derivatives; ligament
(autograft, allograft, and xenograft) and derivatives; derivatives
of intestinal tissue (autograft, allograft, and xenograft),
including for example submucosa; derivatives of stomach tissue
(autograft, allograft, and xenograft), including for example
submucosa; derivatives of bladder tissue (autograft, allograft, and
xenograft), including for example submucosa; derivatives of
alimentary tissue (autograft, allograft, and xenograft), including
for example submucosa; derivatives of respiratory tissue
(autograft, allograft, and xenograft), including for example
submucosa; derivatives of genital tissue (autograft, allograft, and
xenograft), including for example submucosa; derivatives of liver
tissue (autograft, allograft, and xenograft), including for example
liver basement membrane; derivatives of skin tissue; platelet rich
plasma (PRP), platelet poor plasma, bone marrow aspirate,
demineralized bone matrix, insulin derived growth factor, whole
blood, fibrin and blood clot. Purified ECM and other collagen
sources are also intended to be included within "biologically
derived agents." If other such substances have therapeutic value in
the orthopaedic field, it is anticipated that at least some of
these substances will have use in the present invention, and such
substances should be included in the meaning of
"biologically-derived agent" and "biologically-derived agents"
unless expressly limited otherwise.
[0057] "Biologically derived agents" also include bioremodelable
collageneous tissue matrices. The expressions "bioremodelable
collagenous tissue matrix" and "naturally occurring bioremodelable
collageneous tissue matrix" include matrices derived from native
tissue selected from the group consisting of skin, artery, vein,
pericardium, heart valve, dura mater, ligament, bone, cartilage,
bladder, liver, stomach, fascia and intestine, tendon, whatever the
source. Although "naturally occurring bioremodelable collageneous
tissue matrix" is intended to refer to matrix material that has
been cleaned, processed, sterilized, and optionally crosslinked, it
is not within the definition of a naturally occurring
bioremodelable collageneous tissue matrix to purify the natural
fibers and reform a matrix material from purified natural fibers.
The term "bioremodelable collageneous tissue matrices" includes
"extracellular matrices" within its definition.
[0058] "Cells" include one or more of the following: chondrocytes;
fibrochondrocytes; osteocytes; osteoblasts; osteoclasts;
synoviocytes; bone marrow cells; mesenchymal cells; stromal cells;
stem cells; embryonic stem cells; precursor cells derived from
adipose tissue; peripheral blood progenitor cells; stem cells
isolated from adult tissue; genetically transformed cells; a
combination of chondrocytes and other cells; a combination of
osteocytes and other cells; a combination of synoviocytes and other
cells; a combination of bone marrow cells and other cells; a
combination of mesenchymal cells and other cells; a combination of
stromal cells and other cells; a combination of stem cells and
other cells; a combination of embryonic stem cells and other cells;
a combination of precursor cells isolated from adult tissue and
other cells; a combination of peripheral blood progenitor cells and
other cells; a combination of stem cells isolated from adult tissue
and other cells; and a combination of genetically transformed cells
and other cells. If other cells are found to have therapeutic value
in the orthopaedic field, it is anticipated that at least some of
these cells will have use in the present invention, and such cells
should be included within the meaning of "cell" and "cells" unless
expressly limited otherwise. Illustratively, in one example of
embodiments that are to be seeded with living cells such as
chondrocytes, a sterilized implant may be subsequently seeded with
living cells and packaged in an appropriate medium for the cell
type used. For example, a cell culture medium comprising Dulbecco's
Modified Eagles Medium (DMEM) can be used with standard additives
such as non-essential amino acids, glucose, ascorbic acid, sodium
pyruvate, fungicides, antibiotics, etc., in concentrations deemed
appropriate for cell type, shipping conditions, etc.
[0059] "Biocompatible inorganic materials" include materials such
as hydroxyapatite, all calcium phosphates, alpha-tricalcium
phosphate, beta-tricalcium phosphate, calcium carbonate, barium
carbonate, calcium sulfate, barium sulfate, polymorphs of calcium
phosphate, sintered and non-sintered ceramic particles, and
combinations of such materials. If other such substances have
therapeutic value in the orthopaedic field, it is anticipated that
at least some of these substances will have use in the present
invention, and such substances should be included in the meaning of
"biocompatible inorganic material" and "biocompatible inorganic
materials" unless expressly limited otherwise.
[0060] It is expected that various combinations of bioactive
agents, biologically derived agents, cells, biological lubricants,
biocompatible inorganic materials, biocompatible polymers can be
used with the scaffolds and methods of the present invention.
[0061] It is expected that standard disinfection and sterilization
techniques may be used with the products of the present
invention.
EXAMPLE 1
[0062] A defect in goat articular cartilage was repaired with a
device as illustrated in FIG. 11. HA was applied post-operatively
after repairing the defect with a synthetic scaffold according to
FIG. 11. When compared to cartilage defects repaired without HA,
the tissue repaired with both the device and HA appeared to be more
mature, with a whiter, more hyaline-like appearance. Also, the
repaired tissue that is treated with both the device and HA showed
evidence of less severe degradative changes than is seen in the
non-HA treated animals.
[0063] Although the examples all relate to use of HA, it is
expected that other biological lubricants will provide similar
benefits. It should be understood that the nature of the biological
lubricant and the means of administering the biological lubricant
can affect the quality of lubrication provided and can also affect
the biological effects observed. For example, although a biological
lubricant such as HA can be cross-linked to the matrix and still
provide adequate lubrication, some GAG sulfates (e.g. chondroitin
sulfate) can be expected to be less effective, or ineffective, as a
lubricant if cross-linked or co-lyophilized with the underlying
matrix, yet still be used for its biological effects. For some
biological lubricants, it will be desirable to provide the
biological lubricant in a fluidized form to maximize lubrication.
In addition, different materials identified as falling within the
definition of biological lubricants can be expected to have
different efficacies as lubricants and different biological
efficacies. Of the identified biological lubricants, those sharing
properties (e.g. viscosity) similar to those of HA may provide
greater clinical benefit as lubricants. Of the identified
biological lubricants, those decreasing the coefficient of friction
between the implant and healthy cartilage, compared to the case
without the lubricant, are expected to be beneficial, and
particularly those biological lubricants providing a reduced
coefficient of friction for an extended period time. Other of the
identified biological lubricants may provide greater clinical
benefit as biologic agents. It should also be understood that
materials identified as biological lubricants and the means of
administering the material may be combined in various ways to take
advantage of the properties of each and to maximize the clinical
benefits of administering the various materials. Although the
invention has been described in detail with reference to certain
preferred embodiments, variations and modifications exist within
the scope and spirit of the invention as described and defined in
the following claims.
* * * * *