US5786217A
Expired / Lapsed
US
⏱️ 0.0 years remaining
Methods and compositions for the repair of articular cartilage defects in mammals
Assignee: Genzyme Corp
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Filing: 1997-04-14
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Granted: 1998-07-28
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Expires: 2017-04-14
Abstract
Abstract Provided are methods and compositions for the repair of articular cartilage defects in a mammal. Denuded chondrogenic cells are proliferated ex vivo as monolayer cultures in order to expand the pool of available chondrogenic cells. During proliferation the chondrogenic cells stop secreting the extracellular matrix components, type II collagen and sulfated proteoglycans. The proliferated cells then are seeded into a pre-shaped well having a cell contacting, cell abhesive surface. The cells cultured in the well redifferentiate and begin to secrete cartilage-specific extracellular matrix again. Accordingly, essentially unlimited amounts of synthetic cartilage may be prepared from small samples of biopsy tissue. Also provided are methods for surgically repairing articular cartilage defects in mammals using the synthetic cartilage prepared in accordance with the invention.
Inventors
- 👤 Ross A. Tubo
- 👤 Leesa M. Barone
- 👤 Courtney A. Wrenn
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-02 17:02
CPC Classifications
A; A61; A61L; A61L27/00; A61L27/36; A61L27/38; A61L27/3804; A61L27/3817; A61F; A61F2/00; A61F2/02; A61F2/30; A61F2/30756; A61L27/3604; A61L27/3633; A61L27/3641; A61L27/3645; A61L27/3654; A61L27/3839; A61L27/3843; A61L27/3852; C; C12; C12N; C12N5/00; C12N5/06; C12N5/0602; C12N5/0652; C12N5/0655; A61B; A61B17/00; A61B17/00491; A61F2/3094; A61F2/28; A61F2002/2817; A61F2002/30001; A61F2002/30108; A61F2002/3011; A61F2002/30112; A61F2002/30125; A61F2002/30762; A61F2002/30764; A61F2002/30971; A61F2230/00; A61F2230/0002; A61F2230/0004; A61F2230/0008; A61F2240/00; A61F2240/001; A61F2310/00; A61F2310/00005; A61F2310/00365; A61K; A61K35/00; A61K35/12
Claims Analysis
Total Claims: 31
Claim 1
Independent Claim
76 words
A method for preparing a multi cell layered synthetic cartilage patch, the method comprising the steps of: (a) proliferating denuded chondrogenic cells in vitro, wherein said cells are undifferentiated; (b) seeding said cells into a pre-shaped well having a cell contacting surface which prevents attachment of the cells; and (c) culturing said cells for a time sufficient for said cells to differentiate and form a multi cell-layered synthetic cartilage and to endogenously produce an extracellular matrix.
Claim 2
Independent Claim
76 words
A method for preparing a multi cell layered synthetic cartilage patch, the method comprising the steps of: (a) proliferating denuded chondrogenic cells in vitro, wherein said cells are undifferentiated; (b) seeding said cells into a pre-shaped well having a cell contacting surface which prevents attachment of the cells; and (c) culturing said cells for a time sufficient for said cells to differentiate and form a multi cell-layered synthetic cartilage and to endogenously produce an extracellular matrix.
Claim 3
Independent Claim
92 words
A method for preparing a multi cell-layered synthetic cartilage, the method comprising the steps of: (a) providing a tissue comprising interconnected chondrogenic cells; (b) disaggregating said tissue to release denuded chondrogenic cells; (c) proliferating said denuded chondrogenic cell in vitro, wherein said cells are undifferentiated; (d) seeding said cells into a pre-shaped well having a cell contacting surface which prevents attachment of the cells; and (e) culturing said cells for a time sufficient for said cells to differentiate and form a multi cell-layered synthetic cartilage and to endogenously produce an extracellular matrix.
Claim 4
Independent Claim
92 words
A method for preparing a multi cell-layered synthetic cartilage, the method comprising the steps of: (a) providing a tissue comprising interconnected chondrogenic cells; (b) disaggregating said tissue to release denuded chondrogenic cells; (c) proliferating said denuded chondrogenic cell in vitro, wherein said cells are undifferentiated; (d) seeding said cells into a pre-shaped well having a cell contacting surface which prevents attachment of the cells; and (e) culturing said cells for a time sufficient for said cells to differentiate and form a multi cell-layered synthetic cartilage and to endogenously produce an extracellular matrix.
Claim 5
Independent Claim
97 words
A method for preparing a multi cell-layered synthetic cartilage patch of pre-determined volume, the method comprising the steps of: (a) proliferating denuded chondrogenic cells in vitro, wherein said cells are undifferentiated; (b) seeding denuded chondrogenic cells into a pre-shaped well, said well having a cell contacting surface which prevents attachment of the cells and being dimensioned to determine the volume of the resulting synthetic cartilage patch; and (c) culturing said cells for a time sufficient for said cells to differentiate and form a multi cell-layered synthetic cartilage and to endogenously produce an extracellular matrix of pre-determined volume.
Claim 6
Independent Claim
97 words
A method for preparing a multi cell-layered synthetic cartilage patch of pre-determined volume, the method comprising the steps of: (a) proliferating denuded chondrogenic cells in vitro, wherein said cells are undifferentiated; (b) seeding denuded chondrogenic cells into a pre-shaped well, said well having a cell contacting surface which prevents attachment of the cells and being dimensioned to determine the volume of the resulting synthetic cartilage patch; and (c) culturing said cells for a time sufficient for said cells to differentiate and form a multi cell-layered synthetic cartilage and to endogenously produce an extracellular matrix of pre-determined volume.
Claim 7
Independent Claim
112 words
A method for preparing a multi cell-layered synthetic cartilage patch of pre-determined volume, the method comprising the steps of: (a) providing a tissue comprising interconnected chondrogenic cells; (b) disaggregating said tissue to release denuded chrondrogenic cells; (c) proliferating said denuded cells in vitro, wherein said cells are undifferentiated; (d) seeding said cells into a pre-shaped well, said well having a cell contacting surface which prevents attachment of the cells and being dimensioned to determine the volume of the resulting synthetic cartilage; and (e) culturing said cells for a time sufficient for said cells to differentiate and form a multi cell-layered synthetic cartilage and to endogeneously produce an extracellular matrix of pre-determined volume.
Claim 8
Independent Claim
112 words
A method for preparing a multi cell-layered synthetic cartilage patch of pre-determined volume, the method comprising the steps of: (a) providing a tissue comprising interconnected chondrogenic cells; (b) disaggregating said tissue to release denuded chrondrogenic cells; (c) proliferating said denuded cells in vitro, wherein said cells are undifferentiated; (d) seeding said cells into a pre-shaped well, said well having a cell contacting surface which prevents attachment of the cells and being dimensioned to determine the volume of the resulting synthetic cartilage; and (e) culturing said cells for a time sufficient for said cells to differentiate and form a multi cell-layered synthetic cartilage and to endogeneously produce an extracellular matrix of pre-determined volume.
Claim 9
Dependent Claim
20 words
The method of claim 1, 2, 3, or 4, wherein said surface comprises a surface coated with silicon or polytetrafluoroethylene.
Claim 10
Dependent Claim
31 words
The method of claim 1, 2, 3, or 4, wherein said well is defined by a material selected from the group consisting of agarose, glass, untreated cell culture plastic and polytetrafluoroethylene.
Claim 11
Dependent Claim
18 words
The method of claim 1, 2, 3 or 4, wherein said chondrogenic cells are derived from human tissue.
Claim 12
Dependent Claim
17 words
The method of claim 1, 2, 3 or 4, wherein said chondrogenic cells are derived from cartilage.
Claim 13
Dependent Claim
11 words
The method of claim 8, wherein said cartilage is articular cartilage.
Claim 14
Dependent Claim
24 words
The method of claim 8, wherein said cartilage is selected from the group consisting of costal cartilage, nasal cartilage, auricular cartilage and cricoid cartilage.
Claim 15
Dependent Claim
17 words
The method of claim 1, 2, 3, or 4, wherein said extracellular matrix comprises type II collagen.
Claim 16
Dependent Claim
16 words
The method of claim 1, 2, 3, or 4, wherein said extracellular matrix comprises a proteoglycan.
Claim 17
Dependent Claim
13 words
The method of claim 12, wherein said proteoglycan comprises chondroitin-6-sulfate or keratan sulfate.
Claim 18
Dependent Claim
17 words
The method of claim 1, 2, 3, or 4, wherein said synthetic cartilage comprises synthetic articular cartilage.
Claim 19
Dependent Claim
25 words
The method of claim 1, 2, 3 or 4, wherein said well is dimensioned to produce synthetic cartilage that interfits with a mammalian cartilage defect.
Claim 20
Dependent Claim
23 words
The method of claim 1, further comprising an additional step of adding a polypeptide growth factor to the cells cultured in step (b).
Claim 21
Dependent Claim
23 words
The method of claim 2, further comprising an additional step of adding a polypeptide growth factor to the cells cultured in step (e).
Claim 22
Dependent Claim
23 words
The method of claim 3, further comprising an additional step of adding a polypeptide growth factor to the cells cultured in step (b).
Claim 23
Dependent Claim
23 words
The method of claim 4, further comprising an additional step of adding a polypeptide growth factor to the cells cultured in step (e).
Claim 24
Dependent Claim
51 words
The method of claim 16, 17, 18, or 19, wherein said growth factor is selected from the group consisting of transforming growth factor-β, platelet derived growth factor, insulin-like growth factor, acidic fibroblast growth factor, basic fibroblast growth factor, epidermal growth factor, hepatocytic growth factor, keratinocyte growth factor, and bone morphogenic protein.
Claim 25
Dependent Claim
20 words
The method of claim 1, further comprising an additional step of adding ascorbate to the cells cultured in step (b).
Claim 26
Dependent Claim
20 words
The method of claim 2, further comprising an additional step of adding ascorbate to the cells cultured in step (e).
Claim 27
Dependent Claim
20 words
The method of claim 3, further comprising an additional step of adding ascorbate to the cells cultured in step (b).
Claim 28
Dependent Claim
20 words
The method of claim 4, further comprising an additional step of adding ascorbate to the cells cultured in step (e).
Claim 29
Dependent Claim
15 words
A synthetic cartilage patch produced by the method of claim 1, 2, 3, or 4.
Claim 30
Dependent Claim
82 words
A multi cell-layered synthetic articular cartilage patch comprising: chondrogenic cells dispersed within an endogenously produced extracellular matrix, wherein said synthetic articular cartilage is prepared by proliferating denuded chondrogenic cells in vitro, wherein said cells are undifferentiated, seeding chondrogenic cells into a pre-shaped well having a cell contacting surface which prevents attachment of the cells, and culturing said cells in said well for a time sufficient to differentiate and induce formation of synthetic articular cartilage for repairing the cartilage defect in said mammal.
Claim 31
Dependent Claim
82 words
A multi cell-layered synthetic articular cartilage patch comprising: chondrogenic cells dispersed within an endogenously produced extracellular matrix, wherein said synthetic articular cartilage is prepared by proliferating denuded chondrogenic cells in vitro, wherein said cells are undifferentiated, seeding chondrogenic cells into a pre-shaped well having a cell contacting surface which prevents attachment of the cells, and culturing said cells in said well for a time sufficient to differentiate and induce formation of synthetic articular cartilage for repairing the cartilage defect in said mammal.
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USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 2001-07-27 | 2002-01-26 | 2002-07-28 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2005-07-27 | 2006-01-26 | 2006-07-28 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2009-07-27 | 2010-01-26 | 2010-07-28 | $7700.00 | Window Closed / Lapsed |