US6514514B1
Expired / Lapsed
US
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Device and method for regeneration and repair of cartilage lesions
Assignee: Zimmer Orthobiologics Inc
•
Filing: 1999-02-16
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Granted: 2003-02-04
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Expires: 2019-02-16
Abstract
Abstract Disclosed is a cartilage repair product that induces both cell ingrowth into a bioresorbable material and cell differentiation into cartilage tissue. Such a product is useful for regenerating and/or repairing both vascular and avascular cartilage lesions, particularly articular cartilage lesions, and even more particularly mensical tissue lesions, including tears as well as segmental defects. Also disclosed is a method of regenerating and repairing cartilage lesions using such a product.
Inventors
- 👤 Brent Atkinson
- 👤 James J. Benedict
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 11:06
CPC Classifications
A; A61; A61K; A61K9/00; A61K9/48; A61K9/50; A61K9/51; A61K9/5107; A61K9/513; A61K9/5146; A61K9/5153; A61F; A61F2/00; A61F2/02; A61F2/30; A61F2/30756; A61L; A61L27/00; A61L27/14; A61L27/22; A61L27/227; A61L27/24; A61L27/26; A61L27/40; A61L27/44; A61L27/48; A61L27/50; A61L27/54; A61P; A61P19/00; B; B82; B82Y; B82Y5/00; A61B; A61B17/00; A61B17/04; A61B17/06; A61B17/06166; A61F2/28; A61F2002/2817; A61F2002/30001; A61F2002/30003; A61F2002/30004; A61F2002/30036; A61F2002/3006; A61F2002/30062; A61F2002/30667; A61F2002/30677; A61F2210/00; A61F2210/0004; A61F2250/00; A61F2250/0014; A61F2250/0035; A61F2310/00; A61F2310/00005; A61F2310/00365; A61L2300/00; A61L2300/20; A61L2300/252; A61L2300/30; A61L2300/60; A61L2300/62; A61L2300/624; A61L2400/00; A61L2400/12; A61L2430/00; A61L2430/06; Y; Y10; Y10S; Y10S977/00; Y10S977/902; Y10S977/904; Y10S977/908; Y10S977/91; Y10S977/914
Claims Analysis
Total Claims: 63
Claim 1
Independent Claim
183 words
A product for repair meniscal cartilage lesions, comprising: a. a cartilage repair matrix selected from the group consisting of: a matrix configured as a sheet which conforms to a meniscal radial tear, a matrix configured as a sheet which conforms to a meniscal longitudinal tear, a matrix configured as a tapered shape which conforms to a segmental defect in a meniscus, and a matrix configured as a meniscus or a segmental portion thereof; b. a cartilage-inducing composition contained on or within said matrix comprising a mixture of proteins comprising: i. transforming growth factor β (TGFβ) superfamily proteins: TGFβ1, TGFβ2, TGFβ3, bone morphogenetic protein (BMP)-2, BMP-3, BMP-4, BMP-5, BMP-6, BMP-7, and cartilage-derived morphogenetic protein (CDMP); wherein said TGFβ superfamily proteins comprise from about 0.1% to about 50% of said mixture of proteins; ii. bone matrix proteins: osteocalcin, osteonectin, bone sialoprotein (BSP), lysyloxidase, and cathepsin L pre; wherein said bone matrix proteins comprise from about 20% to about 98% of said mixture of proteins; and, iii. fibroblast growth factor-I (FGF-I), wherein said FGF-I comprises from about 0.01% to about 50% of said mixture of proteins.
Claim 2
Dependent Claim
183 words
A product for repair meniscal cartilage lesions, comprising: a. a cartilage repair matrix selected from the group consisting of: a matrix configured as a sheet which conforms to a meniscal radial tear, a matrix configured as a sheet which conforms to a meniscal longitudinal tear, a matrix configured as a tapered shape which conforms to a segmental defect in a meniscus, and a matrix configured as a meniscus or a segmental portion thereof; b. a cartilage-inducing composition contained on or within said matrix comprising a mixture of proteins comprising: i. transforming growth factor β (TGFβ) superfamily proteins: TGFβ1, TGFβ2, TGFβ3, bone morphogenetic protein (BMP)-2, BMP-3, BMP-4, BMP-5, BMP-6, BMP-7, and cartilage-derived morphogenetic protein (CDMP); wherein said TGFβ superfamily proteins comprise from about 0.1% to about 50% of said mixture of proteins; ii. bone matrix proteins: osteocalcin, osteonectin, bone sialoprotein (BSP), lysyloxidase, and cathepsin L pre; wherein said bone matrix proteins comprise from about 20% to about 98% of said mixture of proteins; and, iii. fibroblast growth factor-I (FGF-I), wherein said FGF-I comprises from about 0.01% to about 50% of said mixture of proteins.
Claim 3
Dependent Claim
13 words
The product of claim 1 , wherein said cartilage repair matrix is bioresorbable.
Claim 4
Dependent Claim
13 words
The product of claim 1 , wherein said cartilage repair matrix is porous.
Claim 5
Dependent Claim
28 words
The product of claim 1 , wherein said cartilage repair matrix comprises a material selected from the group consisting of a synthetic polymeric material and a ground substance.
Claim 6
Dependent Claim
21 words
The product of claim 4 , wherein said ground substance is selected from the group consisting of natural polymers and proteoglycans.
Claim 7
Dependent Claim
21 words
The product of claim 5 , wherein said natural polymers are selected from the group consisting of collagen, elastin, and reticulin.
Claim 8
Dependent Claim
25 words
The product of claim 1 , wherein said cartilage repair matrix contains from about 20% to about 100% collagen by dry weight of said matrix.
Claim 9
Dependent Claim
25 words
The product of claim 1 , wherein said cartilage repair matrix contains from about 50% to about 100% collagen by dry weight of said matrix.
Claim 10
Dependent Claim
25 words
The product of claim 1 , wherein said cartilage repair matrix contains from about 75% to about 100% collagen by dry weight of said matrix.
Claim 11
Dependent Claim
31 words
The product of claim 1 , wherein said cartilage repair matrix comprises a collagen-containing material selected from the group consisting of an autograft tissue, an allograft tissue, and a xenograft tissue.
Claim 12
Dependent Claim
16 words
The product of claim 1 , wherein said cartilage repair matrix comprises collagen from bovine tendon.
Claim 13
Dependent Claim
21 words
The product of claim 1 , wherein said matrix is configured as a tapered shape, and wherein said matrix is cross-linked.
Claim 14
Dependent Claim
16 words
The product of claim 12 , wherein said cartilage repair matrix is cross-linked with an aldehyde.
Claim 15
Dependent Claim
18 words
The product of claim 1 , wherein said mixture of proteins further comprises one or more serum proteins.
Claim 16
Dependent Claim
31 words
The product of claim 14 , wherein said serum proteins are selected from the group consisting of albumin, transferrin, α2-Hs GlycoP, IgG, α1-antitrypsin, β2-microglobulin, Apo A1 lipoprotein (LP) and Factor XIIIb.
Claim 17
Dependent Claim
25 words
The product of claim 14 , wherein said serum proteins are selected from the group consisting of albumin, transferrin, Apo A1 LP and Factor XIIIb.
Claim 18
Dependent Claim
26 words
The product of claim 1 , wherein said cartilage-inducing composition is at a concentration of from about 0.5% to about 33% by weight of said product.
Claim 19
Dependent Claim
26 words
The product of claim 1 , wherein said cartilage-inducing composition is at a concentration of from about 1% to about 20% by weight of said product.
Claim 20
Dependent Claim
15 words
The product of claim 1 , wherein said mixture of proteins is bone protein (BP).
Claim 21
Dependent Claim
23 words
The product of claim 1 , wherein said TGFβ superfamily proteins comprise from about 0.5% to about 25% of said mixture of proteins.
Claim 22
Dependent Claim
23 words
The product of claim 1 , wherein said TGFβ superfamily proteins comprise from about 1% to about 10% of said mixture of proteins.
Claim 23
Dependent Claim
23 words
The product of claim 1 , wherein said bone matrix proteins comprise from about 40% to about 98% of said mixture of proteins.
Claim 24
Dependent Claim
23 words
The product of claim 1 , wherein said bone matrix proteins comprise from about 80% to about 98% of said mixture of proteins.
Claim 25
Dependent Claim
21 words
The product of claim 1 , wherein said FGF-I comprises from about 0.1% to about 10% of said mixture of proteins.
Claim 26
Dependent Claim
26 words
The product of claim 1 , wherein said lesion is within meniscal cartilage selected from the group consisting of vascular meniscal cartilage and avascular meniscal cartilage.
Claim 27
Dependent Claim
45 words
The product of claim 1 , wherein said cartilage inducing composition has an identifying characteristic selected from the group consisting of an ability to induce cellular infiltration, an ability to induce cellular proliferation, and an ability to induce cellular differentiation to type II collagen-producing chondrocytes.
Claim 28
Dependent Claim
23 words
The product of claim 1 , wherein said cartilage-inducing composition further comprises a glycosaminoglycan that non-covalently attaches to said proteins in said composition.
Claim 29
Dependent Claim
36 words
The product of claim 1 , wherein said cartilage repair matrix comprises a material selected from the group consisting of poly(lactic acid), poly(glycolic acid), type I collagen, type II collagen, type IV collagen and hyaluronic acid.
Claim 30
Dependent Claim
30 words
The product of claim 1 , wherein said matrix is configured as a sheet, and wherein said sheet has a thickness of from about 0.1 mm to about 3 mm.
Claim 31
Dependent Claim
30 words
The product of claim 1 , wherein said matrix is configured as a sheet, and wherein said sheet has a thickness of from about 0.5 mm to about 2 mm.
Claim 32
Dependent Claim
34 words
The product of claim 1 , wherein said matrix is configured as a sheet, and wherein said sheet is prepared from an aqueous dispersion of from about 0.2% to about 4% collagen by weight.
Claim 33
Dependent Claim
34 words
The product of claim 1 , wherein said matrix is configured as a sheet, and wherein said sheet is prepared from an aqueous dispersion of from about 0.5% to about 3% collagen by weight.
Claim 34
Dependent Claim
35 words
The product of claim 1 , wherein said cartilage repair matrix is configured as a sheet, and wherein said sheet is porous, having a pore diameter of from about 10 μm to about 100 μm.
Claim 35
Dependent Claim
44 words
The product of claim 1 , wherein said matrix is configured as a tapered shape which varies in thickness from about 0.5 mm to about 3 mm at its thinnest region to from about 4 mm to about 10 mm at its thickest region.
Claim 36
Dependent Claim
35 words
The product of claim 1 , wherein said matrix is configured as a tapered shape, and wherein said matrix has a density of from about 0.07 to about 0.5 grams matrix per cm 3 .
Claim 37
Dependent Claim
35 words
The product of claim 1 , wherein said matrix is configured as a tapered shape, and wherein said matrix has a density of from about 0.1 to about 0.25 grams matrix per cm 3 .
Claim 38
Dependent Claim
36 words
The product of claim 1 , wherein said matrix is configured as a tapered shape, and wherein said cartilage repair matrix is porous, having a pore diameter of from about 50 μm to about 500 μm.
Claim 39
Dependent Claim
30 words
The product of claim 1 , wherein said matrix is configured as a tapered shape, and wherein said cartilage repair matrix comprises a porous ground substance composite which includes collagen.
Claim 40
Dependent Claim
38 words
The product of claim 12 , wherein said matrix is cross-linked by an agent selected from the group consisting of formaldehyde, glutaraldehyde, dimethyl suberimidate, carbodiimides, multi-functional epoxides, succinimidyls, poly(glycidyl ether), diisocyanates, acyl azide, tris(hydroxymethyl)phosphine, ascorbate-copper, glucose-lysine and photo-oxidizers.
Claim 41
Dependent Claim
25 words
The product of claim 12 , wherein said matrix is cross-linked by a method selected from the group consisting of: ultraviolet irradiation and dehydrothermal treatment.
Claim 42
Dependent Claim
51 words
The product of claim 1 , wherein said cartilage-inducing composition is contained on or within said cartilage repair matrix by a method selected from the group consisting of freeze-drying said composition onto a surface of said matrix and suspension within said cartilage repair matrix of a delivery formulation containing said composition.
Claim 43
Dependent Claim
21 words
The product of claim 1 , wherein said FGF-I comprises from about 0.05% to about 25% of said mixture of proteins.
Claim 44
Independent Claim
136 words
A method for repair of meniscal cartilage lesions, comprising implanting and fixing into a meniscal cartilage lesion a product comprising: a. a cartilage repair matrix; and b. a cartilage-inducing composition contained on or within said matrix comprising a mixture of proteins comprising: i. transforming growth factor β (TGFβ) superfamily proteins: TGFβ1, TGFβ2, TGFβ3, bone morphogenetic protein (BMP)-2, BMP-3, BMP4, BMP-5, BMP-6, BMP-7, and cartilage-derived morphogenetic protein (CDMP); wherein said TGFβ superfamily proteins comprise from about 0.1% to about 50% of said mixture of proteins; ii. bone matrix proteins: osteocalcin, osteonectin, bone sialoprotein (BSP), lysyloxidase, and cathepsin L pre; wherein said bone matrix proteins comprise from about 20% to about 98% of said mixture of proteins; and, iii. fibroblast growth factor-I (FGF-I), wherein said FGF-I comprises from about 0.01% to about 50% of said mixture of proteins.
Claim 45
Independent Claim
136 words
A method for repair of meniscal cartilage lesions, comprising implanting and fixing into a meniscal cartilage lesion a product comprising: a. a cartilage repair matrix; and b. a cartilage-inducing composition contained on or within said matrix comprising a mixture of proteins comprising: i. transforming growth factor β (TGFβ) superfamily proteins: TGFβ1, TGFβ2, TGFβ3, bone morphogenetic protein (BMP)-2, BMP-3, BMP4, BMP-5, BMP-6, BMP-7, and cartilage-derived morphogenetic protein (CDMP); wherein said TGFβ superfamily proteins comprise from about 0.1% to about 50% of said mixture of proteins; ii. bone matrix proteins: osteocalcin, osteonectin, bone sialoprotein (BSP), lysyloxidase, and cathepsin L pre; wherein said bone matrix proteins comprise from about 20% to about 98% of said mixture of proteins; and, iii. fibroblast growth factor-I (FGF-I), wherein said FGF-I comprises from about 0.01% to about 50% of said mixture of proteins.
Claim 46
Dependent Claim
34 words
The method of claim 43 , wherein said lesion is a tear and wherein said matrix is configured as a sheet, wherein said step of implanting comprises inserting said product directly into said tear.
Claim 47
Dependent Claim
36 words
The method of claim 43 , wherein said product is fixed into said lesion by an attachment means selected from the group consisting of bioresorbable sutures, non-resorbable sutures, press-fitting, arrows, nails, and T-fix suture anchor devices.
Claim 48
Dependent Claim
14 words
The method of claim 43 , wherein said lesion is a vascular meniscus lesion.
Claim 49
Dependent Claim
14 words
The method of claim 43 , wherein said lesion is an avascular meniscus lesion.
Claim 50
Dependent Claim
14 words
The method of claim 43 , wherein said lesion is a meniscal radial tear.
Claim 51
Dependent Claim
15 words
The method of claim 43 , wherein said lesion is a meniscal bucket handle tear.
Claim 52
Dependent Claim
14 words
The method of claim 43 , wherein said lesion is a meniscal segmental defect.
Claim 53
Dependent Claim
175 words
A product for repair of vascular and avascular meniscus tears, comprising: a. a cartilage repair matrix comprising collagen selected from the group consisting of: a matrix configured as a sheet which conforms to a meniscal radial tear, a matrix configured as a sheet which conforms to a meniscal bucket handle tear, a matrix configured as a sheet which conforms to a meniscal longitudinal tear; and b. a cartilage-inducing composition contained on or within said matrix comprising a mixture of proteins comprising: i. transforming growth factor β (TGFβ) superfamily proteins: TGFβ1, TGFβ2, TGFβ3, bone morphogenetic protein (BMP)-2, BMP-3, BMP-4, BMP-5, BMP-6, BMP-7, and cartilage-derived morphogenetic protein (CDMP); wherein said TGFβ superfamily proteins comprise from about 0.1% to about 50% of said mixture of proteins; ii. bone matrix proteins: osteocalcin, osteonectin, bone sialoprotein (BSP), lysyloxidase, and cathepsin L pre; wherein said bone matrix proteins comprise from about 20% to about 98% of said mixture of proteins; and, iii. fibroblast growth factor-I (FGF-I), wherein said FGF-I comprises from about 0.01% to about 50% of said mixture of proteins.
Claim 54
Dependent Claim
175 words
A product for repair of vascular and avascular meniscus tears, comprising: a. a cartilage repair matrix comprising collagen selected from the group consisting of: a matrix configured as a sheet which conforms to a meniscal radial tear, a matrix configured as a sheet which conforms to a meniscal bucket handle tear, a matrix configured as a sheet which conforms to a meniscal longitudinal tear; and b. a cartilage-inducing composition contained on or within said matrix comprising a mixture of proteins comprising: i. transforming growth factor β (TGFβ) superfamily proteins: TGFβ1, TGFβ2, TGFβ3, bone morphogenetic protein (BMP)-2, BMP-3, BMP-4, BMP-5, BMP-6, BMP-7, and cartilage-derived morphogenetic protein (CDMP); wherein said TGFβ superfamily proteins comprise from about 0.1% to about 50% of said mixture of proteins; ii. bone matrix proteins: osteocalcin, osteonectin, bone sialoprotein (BSP), lysyloxidase, and cathepsin L pre; wherein said bone matrix proteins comprise from about 20% to about 98% of said mixture of proteins; and, iii. fibroblast growth factor-I (FGF-I), wherein said FGF-I comprises from about 0.01% to about 50% of said mixture of proteins.
Claim 55
Dependent Claim
19 words
The product of claim 51 , wherein said sheet is of a shape and size complementary to said tear.
Claim 56
Dependent Claim
23 words
The product of claim 51 , wherein said tear is an avascular tear and said composition further comprises a time controlled delivery formulation.
Claim 57
Independent Claim
149 words
A method for repair of vascular meniscus lesions, comprising implanting and fixing into a cartilage lesion in the vascular region of a meniscus a product comprising: a. a cartilage repair matrix comprising collagen and configured as a sheet; and b. a cartilage-inducing composition contained on or within said matrix comprising a mixture of proteins comprising: i. transforming growth factor β (TGFβ) superfamily proteins: TGFβ1, TGFβ2, TGFβ3, bone morphogenetic protein (BMP)-2, BMP-3, BMP-4, BMP-5, BMP-6, BMP-7, and cartilage-derived morphogenetic protein (CDMP); wherein said TGFβ superfamily proteins comprise from about 0.1% to about 50% of said mixture of proteins; ii. bone matrix proteins: osteocalcin, osteonectin, bone sialoprotein (BSP), lysyloxidase, and cathepsin L pre; wherein said bone matrix proteins comprise from about 20% to about 98% of said mixture of proteins; and, iii. fibroblast growth factor-I (FGF-I), wherein said FGF-I comprises from about 0.01% to about 50% of said mixture of proteins.
Claim 58
Independent Claim
149 words
A method for repair of vascular meniscus lesions, comprising implanting and fixing into a cartilage lesion in the vascular region of a meniscus a product comprising: a. a cartilage repair matrix comprising collagen and configured as a sheet; and b. a cartilage-inducing composition contained on or within said matrix comprising a mixture of proteins comprising: i. transforming growth factor β (TGFβ) superfamily proteins: TGFβ1, TGFβ2, TGFβ3, bone morphogenetic protein (BMP)-2, BMP-3, BMP-4, BMP-5, BMP-6, BMP-7, and cartilage-derived morphogenetic protein (CDMP); wherein said TGFβ superfamily proteins comprise from about 0.1% to about 50% of said mixture of proteins; ii. bone matrix proteins: osteocalcin, osteonectin, bone sialoprotein (BSP), lysyloxidase, and cathepsin L pre; wherein said bone matrix proteins comprise from about 20% to about 98% of said mixture of proteins; and, iii. fibroblast growth factor-I (FGF-I), wherein said FGF-I comprises from about 0.01% to about 50% of said mixture of proteins.
Claim 59
Dependent Claim
37 words
The method of claim 54 , wherein the rate of repair of said vascular mensicus lesion is measurably enhanced as compared to the rate of repair of a meniscus lesion repaired in the absence of said product.
Claim 60
Dependent Claim
37 words
The method of claim 54 , wherein the quality of repair of said vascular mensicus lesion is measurably enhanced as compared to the quality of repair of a meniscus lesion repaired in the absence of said product.
Claim 61
Dependent Claim
137 words
A product for repair of meniscal cartilage lesions, comprising: a. a cartilage repair matrix selected from the group consisting of: a matrix configured as a sheet which conforms to a meniscal radial tear, a matrix configured as a sheet which conforms to a meniscal bucket handle tear, a matrix configured as a sheet which conforms to a meniscal longitudinal tear, a matrix configured as a tapered shape which conforms to a segmental defect in a meniscus, and a matrix configured as a meniscus or a segmental portion thereof; and b. a cartilage-inducing composition associated with said matrix, said composition comprising at least BMP-3, BMP-2 and TGFβ1, wherein the quantity of BMP-3 in said composition is about 2-6 fold greater than the quantity of BMP-2 and about 10-30 fold greater than the quantity of TGFP1 in said composition.
Claim 62
Dependent Claim
137 words
A product for repair of meniscal cartilage lesions, comprising: a. a cartilage repair matrix selected from the group consisting of: a matrix configured as a sheet which conforms to a meniscal radial tear, a matrix configured as a sheet which conforms to a meniscal bucket handle tear, a matrix configured as a sheet which conforms to a meniscal longitudinal tear, a matrix configured as a tapered shape which conforms to a segmental defect in a meniscus, and a matrix configured as a meniscus or a segmental portion thereof; and b. a cartilage-inducing composition associated with said matrix, said composition comprising at least BMP-3, BMP-2 and TGFβ1, wherein the quantity of BMP-3 in said composition is about 2-6 fold greater than the quantity of BMP-2 and about 10-30 fold greater than the quantity of TGFP1 in said composition.
Claim 63
Dependent Claim
59 words
The product of claim 57 , wherein said composition further comprises: (i) bone matrix proteins: osteocalcin, osteonectin, bone sialoprotein (BSP), lysyloxidase, and cathepsin L pre; wherein said bone matrix proteins comprise from about 20% to about 98% of said composition; and, (ii) fibroblast growth factor-I (FGF-I), wherein said FGF-I comprises from about 0.01% to about 50% of said composition.
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