US5928945A
Expired / Lapsed
US
⏱️ 0.0 years remaining
Application of shear flow stress to chondrocytes or chondrocyte stem cells to produce cartilage
Assignee: Smith and Nephew Inc
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Filing: 1996-11-20
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Granted: 1999-07-27
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Expires: 2016-11-20
Abstract
Abstract Mammalian cells capable of producing cartilage are cultured under a shear flow stress of about 1 to about 100 dynes/cm 2 to produce artificial cartilage for surgical transplantation to replace damaged or missing cartilage. Shear flow stressed cells display enhanced maintenance of chondrocyte phenotype and produce an extracellular matrix containing an enhanced ratio of type II collagen to type I collagen. The cells may be chondrocytes, chondrocyte stem cells or cells such as myoblasts or fibroblasts that transdifferentiate into chondrocytes. A bioreactor is used containing a growth chamber having a substrate on which the cells capable of producing cartilage are attached, and means for applying relative movement between a liquid culture medium and the substrate to provide the shear flow stress. The substrate may be a scaffold, or a nonporous surface such as the surface of a rotatable drum or disc, or the surface of a static plate that supports cell growth in a monolayer. Cartilage is produced by covering the substrate with a liquid growth medium, inoculating into the medium cells capable of producing cartilage, allowing the cells to attach to the substrate, applying and maintaining relative movement between the growth medium and the cells to provide the shear flow stress to produce shear flow stressed cells, and culturing the shear flow stressed cells to produce cartilage.
Inventors
- 👤 Dror Seliktar
- 👤 Noushin Dunkelman
- 👤 Alvin Edward Peterson
- 👤 Ronda Elizabeth Schreiber
- 👤 Jane Willoughby
- 👤 Gail K. Naughton
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-30 00:47
CPC Classifications
C; C12; C12N; C12N5/00; C12N5/06; C12N5/0602; C12N5/0652; C12N5/0655; C12M; C12M21/00; C12M21/08; C12M25/00; C12M25/14; C12M35/00; C12M35/04
Claims Analysis
Total Claims: 26
Claim 1
Independent Claim
56 words
A bioreactor for producing cartilage comprising a growth chamber, a substrate on which chondrocyte cells or chondrocyte stem cells are attached, and means for applying relative movement between a liquid culture medium and the substrate to provide a shear flow stress of about 1 to about 100 dynes/cm 2 to the cells attached to said substrate.
Claim 2
Dependent Claim
56 words
A bioreactor for producing cartilage comprising a growth chamber, a substrate on which chondrocyte cells or chondrocyte stem cells are attached, and means for applying relative movement between a liquid culture medium and the substrate to provide a shear flow stress of about 1 to about 100 dynes/cm 2 to the cells attached to said substrate.
Claim 3
Dependent Claim
23 words
The bioreactor of claim 1, further comprising a means for applying shear flow stress of about 1 to about 50 dynes/cm 2 .
Claim 4
Dependent Claim
59 words
The bioreactor of claim 1, wherein said means for applying shear flow stress comprises a reservoir, a pump, and tubing interconnecting said growth chamber, said reservoir, and said pump, so as to allow continuous flow of liquid growth medium from said reservoir, through said growth chamber, and back to said reservoir, in response to force applied by said pump.
Claim 5
Dependent Claim
11 words
The bioreactor of claim 1, wherein said substrate is a scaffold.
Claim 6
Dependent Claim
10 words
The bioreactor of claim 4, wherein said scaffold is bioabsorbable.
Claim 7
Dependent Claim
22 words
The bioreactor of claim 1, wherein said substrate is a nonporous surface that supports the growth of said cells in a monolayer.
Claim 8
Dependent Claim
16 words
The bioreactor of claim 6, wherein said nonporous surface is the surface of a rotatable drum.
Claim 9
Dependent Claim
16 words
The bioreactor of claim 6, wherein said nonporous surface is the surface of a rotatable disc.
Claim 10
Dependent Claim
13 words
The bioreactor of claim 6, wherein said nonporous surface is a static plate.
Claim 11
Dependent Claim
10 words
The bioreactor of claim 4, wherein the scaffold is biocompatible.
Claim 12
Dependent Claim
10 words
The bioreactor of claim 10, wherein the scaffold is biodegradable.
Claim 13
Dependent Claim
10 words
The bioreactor of claim 10, wherein the scaffold is non-biodegradable.
Claim 14
Independent Claim
107 words
A method for producing cartilage, said method comprising the steps of: (a) providing a growth chamber comprising a substrate for cell attachment; (b) covering said substrate with a liquid growth medium; (c) inoculating chondrocyte cells or chondrocyte stem cells into said medium; (d) allowing said cells to attach to said substrate; (e) applying and maintaining relative movement between the liquid growth medium and the cells attached to the substrate to provide a shear flow stress of about 1 to about 100 dynes/cm 2 to said cells, thereby producing shear flow stressed cells; and (f) culturing said shear flow stressed cells for a time sufficient to produce cartilage.
Claim 15
Independent Claim
107 words
A method for producing cartilage, said method comprising the steps of: (a) providing a growth chamber comprising a substrate for cell attachment; (b) covering said substrate with a liquid growth medium; (c) inoculating chondrocyte cells or chondrocyte stem cells into said medium; (d) allowing said cells to attach to said substrate; (e) applying and maintaining relative movement between the liquid growth medium and the cells attached to the substrate to provide a shear flow stress of about 1 to about 100 dynes/cm 2 to said cells, thereby producing shear flow stressed cells; and (f) culturing said shear flow stressed cells for a time sufficient to produce cartilage.
Claim 16
Dependent Claim
19 words
The method of claim 13, wherein said shear flow stress is about 1 to about 50 dynes/cm 2 .
Claim 17
Dependent Claim
11 words
The method of claim 13, wherein said substrate is a scaffold.
Claim 18
Dependent Claim
10 words
The method of claim 15, wherein said scaffold is bioabsorbable.
Claim 19
Dependent Claim
22 words
The method of claim 13, wherein said substrate is a nonporous surface that supports the growth of said cells in a monolayer.
Claim 20
Dependent Claim
16 words
The method of claim 17, wherein said nonporous surface is the surface of a rotatable drum.
Claim 21
Dependent Claim
16 words
The method of claim 17, wherein said nonporous surface is the surface of a rotatable disc.
Claim 22
Dependent Claim
13 words
The method of claim 17, wherein said nonporous surface is a static plate.
Claim 23
Dependent Claim
37 words
The method of claim 13, wherein said shear flow stressed cells: (a) display enhanced maintenance of a chondrocyte phenotype; and (b) produce an extracellular matrix containing an enhanced ratio of type II collagen to type I collagen.
Claim 24
Dependent Claim
10 words
The method of claim 15, wherein the scaffold is biocompatible.
Claim 25
Dependent Claim
10 words
The method of claim 22, wherein the scaffold is biodegradable.
Claim 26
Dependent Claim
10 words
The method of claim 22, wherein the scaffold is non-biodegradable.
References Cited (Backward Citations)
US5041138A
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 2002-07-26 | 2003-01-25 | 2003-07-27 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2006-07-26 | 2007-01-25 | 2007-07-27 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2010-07-26 | 2011-01-25 | 2011-07-27 | $7700.00 | Window Closed / Lapsed |