WO1998050017B1 - Poly(vinyl alcohol) cryogel - Google Patents
Poly(vinyl alcohol) cryogelInfo
- Publication number
- WO1998050017B1 WO1998050017B1 PCT/US1998/009129 US9809129W WO9850017B1 WO 1998050017 B1 WO1998050017 B1 WO 1998050017B1 US 9809129 W US9809129 W US 9809129W WO 9850017 B1 WO9850017 B1 WO 9850017B1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- pva
- polymer mixture
- cryogel
- pva polymer
- approximately
- Prior art date
Links
- 229920002451 polyvinyl alcohol Polymers 0.000 title claims abstract 64
- 239000000495 cryogel Substances 0.000 title claims 23
- -1 Poly(vinyl alcohol) Polymers 0.000 title abstract 2
- 238000000034 method Methods 0.000 claims abstract 35
- 210000001519 tissues Anatomy 0.000 claims abstract 7
- 239000002407 tissue scaffold Substances 0.000 claims abstract 3
- 235000019422 polyvinyl alcohol Nutrition 0.000 claims 62
- 229920002959 polymer blend Polymers 0.000 claims 25
- 238000007710 freezing Methods 0.000 claims 10
- 238000010257 thawing Methods 0.000 claims 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims 9
- 229920000642 polymer Polymers 0.000 claims 8
- 230000000975 bioactive Effects 0.000 claims 7
- 239000003795 chemical substances by application Substances 0.000 claims 7
- 238000004519 manufacturing process Methods 0.000 claims 6
- 239000007858 starting material Substances 0.000 claims 6
- 239000000243 solution Substances 0.000 claims 5
- 239000003814 drug Substances 0.000 claims 4
- 229940079593 drugs Drugs 0.000 claims 4
- 210000003527 eukaryotic cell Anatomy 0.000 claims 4
- 239000000843 powder Substances 0.000 claims 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims 4
- 229940089114 Drug Delivery Device Drugs 0.000 claims 3
- 230000010261 cell growth Effects 0.000 claims 3
- 239000003292 glue Substances 0.000 claims 3
- 239000003112 inhibitor Substances 0.000 claims 3
- 230000002401 inhibitory effect Effects 0.000 claims 3
- 239000011148 porous material Substances 0.000 claims 3
- 230000035755 proliferation Effects 0.000 claims 3
- 239000011780 sodium chloride Substances 0.000 claims 3
- 210000000988 Bone and Bones Anatomy 0.000 claims 2
- 102000008186 Collagen Human genes 0.000 claims 2
- 108010035532 Collagen Proteins 0.000 claims 2
- 229920002683 Glycosaminoglycan Polymers 0.000 claims 2
- 229960005188 collagen Drugs 0.000 claims 2
- 229920001436 collagen Polymers 0.000 claims 2
- 238000009792 diffusion process Methods 0.000 claims 2
- 210000002950 fibroblast Anatomy 0.000 claims 2
- 238000006460 hydrolysis reaction Methods 0.000 claims 2
- 102000006495 integrins Human genes 0.000 claims 2
- 108010044426 integrins Proteins 0.000 claims 2
- 239000011159 matrix material Substances 0.000 claims 2
- NKCXQMYPWXSLIZ-PSRDDEIFSA-N (2S)-2-[[(2S)-1-[(2S)-5-amino-2-[[2-[[(2S)-6-amino-2-[[2-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S,3R)-2-amino-3-hydroxybutanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-3-hydroxybutanoyl]amino]propanoyl]amino]-4-oxobutanoyl]amino]-3-m Chemical compound O=C([C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CCCCN)NC(=O)CNC(=O)[C@@H](NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@@H](N)[C@@H](C)O)[C@@H](C)O)C(C)C)N1CCC[C@H]1C(=O)N[C@@H](CO)C(O)=O NKCXQMYPWXSLIZ-PSRDDEIFSA-N 0.000 claims 1
- 210000000845 Cartilage Anatomy 0.000 claims 1
- 210000001608 Connective Tissue Cells Anatomy 0.000 claims 1
- 102000004127 Cytokines Human genes 0.000 claims 1
- 108090000695 Cytokines Proteins 0.000 claims 1
- 102000033147 ERVK-25 Human genes 0.000 claims 1
- 210000002889 Endothelial Cells Anatomy 0.000 claims 1
- ZFGMDIBRIDKWMY-PASTXAENSA-N Heparin Chemical compound CC(O)=N[C@@H]1[C@@H](O)[C@H](O)[C@@H](COS(O)(=O)=O)O[C@@H]1O[C@@H]1[C@@H](C(O)=O)O[C@@H](O[C@H]2[C@@H]([C@@H](OS(O)(=O)=O)[C@@H](O[C@@H]3[C@@H](OC(O)[C@H](OS(O)(=O)=O)[C@H]3O)C(O)=O)O[C@@H]2O)CS(O)(=O)=O)[C@H](O)[C@H]1O ZFGMDIBRIDKWMY-PASTXAENSA-N 0.000 claims 1
- 229960002897 Heparin Drugs 0.000 claims 1
- 210000000329 Myocytes, Smooth Muscle Anatomy 0.000 claims 1
- 108091005771 Peptidases Proteins 0.000 claims 1
- 239000004365 Protease Substances 0.000 claims 1
- 101700006801 THBI Proteins 0.000 claims 1
- 108090000190 Thrombin Proteins 0.000 claims 1
- 230000002429 anti-coagulation Effects 0.000 claims 1
- 102000004965 antibodies Human genes 0.000 claims 1
- 108090001123 antibodies Proteins 0.000 claims 1
- 239000003146 anticoagulant agent Substances 0.000 claims 1
- 210000002403 aortic endothelial cell Anatomy 0.000 claims 1
- 239000007864 aqueous solution Substances 0.000 claims 1
- 210000004027 cells Anatomy 0.000 claims 1
- 238000004132 cross linking Methods 0.000 claims 1
- 230000002500 effect on skin Effects 0.000 claims 1
- 239000003102 growth factor Substances 0.000 claims 1
- 229920000669 heparin Polymers 0.000 claims 1
- 230000003204 osmotic Effects 0.000 claims 1
- 238000006116 polymerization reaction Methods 0.000 claims 1
- 230000001737 promoting Effects 0.000 claims 1
- 229960004072 thrombin Drugs 0.000 claims 1
- 239000003868 thrombin inhibitor Substances 0.000 claims 1
- 239000000017 hydrogel Substances 0.000 abstract 3
- 238000006297 dehydration reaction Methods 0.000 abstract 1
- 238000002513 implantation Methods 0.000 abstract 1
Abstract
The present invention comprises a poly(vinyl alcohol) hydrogel construct having a wide range of mechanical strengths for use as a human tissue replacement. A process in connection with the present invention eliminates any step involved with dehydration of the hydrogel prior to implantation thereof. The hydrogel construct may comprise a tissue scaffolding, a low bearing surface within a joint, or any other structure which is suitable for supporting the growth of tissue.
Claims
1. A process for preparing a PVA construct comprising the steps of : pouring an aqueous PVA polymer mixture into a mold; freezing and thawing said PVA polymer mixture within said mold at least once to create an interlocking mesh between PVA polymer molecules to create the PVA cryogel ; removing, at least partially, said PVA cryogel from said mold; immersing said PVA cryogel in an aqueous solution; and freezing and thawing said PVA cryogel at least once while immersed in water.
2. The process of claim 1, comprising the further step, before immersing said PVA cryogel in water, of: removing, at least partially, said PVA cryogel from said mold.
3. The process of claim 1, wherein said aqueous PVA polymer mixture comprises a PVA polymer starting material having a molecular weight ranging from approximately 11,000 to approximately 500,000.
4. The process of claim 1, wherein said aqueous PVA polymer mixture is biocompatible and comprises a PVA polymer starting material in the form of a dry powder.
5. The process of claim 1, wherein said aqueous PVA polymer mixture comprises a PVA starting material in the form of a dry powder, and further wherein a degree of polymerization of the PVA starting material ranges from approximately 500 to approximately 3500.
26
6. The process of claim 1, wherein said aqueous PVA polymer mixture comprises a PVA starting material in the form of a dry powder with a degree of hydrolysis in excess of approximately 80 percent.
7. The process of claim 1, wherein said aqueous PVA polymer mixture comprises a PVA starting material in the form of a dry powder with a degree of hydrolysis in excess of approximately 99 percent.
8. The process of claim 1, wherein said aqueous PVA polymer mixture comprises approximately 2 to approximately 40 parts by weight PVA and approximately 98 to approximately 60' parts by weight water.
9. The process of claim 1, wherein said aqueous PVA polymer mixture comprises approximately 20 to approximately 40 parts by weight PVA and approximately 60 to approximately 80 parts by weight water.
10. The process of claim 1, wherein said aqueous PVA polymer mixture comprises an isotonic saline solution to prevent osmotic imbalances between the tissue replacement and surrounding tissues.
11. The process of claim 1, wherein said isotonic saline solution comprises approximately 0.9 percent NaCl and approximately 99.1 percent water.
12. A process for preparing a biocompatible drug delivery device wherein the number of pores and degree of intermolecular meshing may be varied to regulate the drug release rate from said delivery device, the process comprising the steps of: preparing an aqueous PVA polymer mixture;
pouring said PVA polymer mixture into a mold; and freezing and thawing said PVA polymer mixture within said mold at least twice to create an interlocking mesh between PVA polymer molecules to create the PVA cryogel .
13. A process for preparing a biocompatible drug delivery device wherein the number of pores and degree of intermolecular meshing may be varied to regulate the drug release rate from said delivery device, the process comprising the steps of: preparing an aqueous PVA polymer mixture containing a drug; pouring said PVA polymer mixture into a mold; freezing and thawing said PVA polymer mixture within said mold at least once to create an interlocking mesh between PVA polymer molecules to create the PVA cryogel; immersing said PVA cryogel in water; and freezing and thawing said PVA cryogel at least once while immersed in water.
14. A process for preparing a biocompatible drug delivery device wherein the number of pores and degree of intermolecular meshing may be varied to regulate the drug release rate from said delivery device, the process comprising the steps of: preparing an aqueous PVA polymer mixture; pouring said PVA polymer mixture into a mold; freezing and thawing said PVA polymer mixture within said mold at least once to create an interlocking mesh between PVA polymer molecules to create the PVA cryogel; and immersing said PVA cryogel in a solution containing a bioactive agent to promote diffusion of said bioactive agent into said PVA cryogel .
15. A process for preparing a biocompatible construct that promotes cellular growth and proliferation on the surface of the construct, the process comprising the steps of: preparing an aqueous PVA polymer mixture containing a bioactive agent to promote cellular growth and proliferation; pouring said PVA polymer mixture into a mold; and freezing and thawing said PVA polymer mixture within said mold at least once to create an interlocking mesh between PVA polymer molecules to create the PVA cryogel .
16. The process of claim 15, further comprising the steps of: immersing said PVA cryogel in water; and freezing and thawing said PVA cryogel at least once while immersed in water.
17. The process of claim 15, wherein said bioactive agent to support cellular growth and proliferation is selected from the group consisting of: growth factors, collagen cross-linking inhibitors, matrix inhibitors, cytokines, integrins, and glycosaminoglycans .
18. A process for preparing a biocompatible construct incorporating eukaryotic cells, the process comprising the steps of : preparing an aqueous PVA polymer mixture; pouring said PVA polymer mixture into a mold; freezing and thawing said PVA polymer mixture within said mold at least once to create an interlocking mesh between PVA polymer molecules to create the PVA cryogel; and immersing said PVA cryogel in a solution containing eukaryotic cells to promote diffusion of said cells into said PVA cryogel.
19. The process of claim 18, further comprising the step of: freezing and thawing said PVA cryogel at least once while immersed in said solution containing a bioactive agent.
20. A PVA cryogel which contains eukaryotic cells.
21. The PVA cryogel of claim 20, wherein said eukaryotic cells are selected from the group consisting of : endothelial cells, aortic endothelial cells, smooth muscle cells, fibroblasts, dermal fibroblasts, and connective tissue cells.
22. The product according to the process of claim 1.
23. The product of claim 22, further comprising a bioactive agent.
24. The product of claim 23, wherein said bioactive agent is selected from the group consisting of: a heparin, a βAPN, an antibody, a cytokine, an integrin, a protease, a matrix inhibitor, an anticoagulant, a sphyngolipid, a thrombin, a thrombin inhibitor, and a glycosaminoglycan .
25. The product of claim 1 comprising a tissue replacement .
26. The product of claim 1 comprising a tissue scaffold.
27. The product of claim 26 wherein said tissue scaffold has an open-celled structure for promoting tissue ingrowth.
28. The product of claim 1 comprising a tissue expander.
29. The product of claim 1 comprising an implantable articulating surface for a load bearing joint.
30. The product of claim 29 wherein the articulating surface is fixed to bone with internal fixators comprising at least one of screws or sutures .
31. The product of claim 29 wherein the articulating surface is arranged and configured to be fixed to bone with a glue .
32. The product of claim 30 wherein the glue comprises a collagen glue.
33. The product of claim 1 comprising a cartilage replacement.
34. The product according to the process of claim 2.
35. The product according to the process of claim 3.
36. The product according to the process of claim 4.
37. The product according to the process of claim 5.
38. The product according to the process of claim 6.
39. The product according to the process of claim 7.
40. The product according to the process of claim 10.
41. The product according to the process of claim 12.
42. The product according to the process of claim 13.
43. The product according to the process of claim 14.
44. The product according to the process of claim 15.
45. The product according to the process of claim 16
46. The product according to the process of claim 17
47. The product according to the process of claim 18
48. The product according to the process of claim 19.
Priority Applications (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP54838198A JP3506718B2 (en) | 1997-05-05 | 1998-05-05 | Poly (vinyl alcohol) cryogel |
| AU71766/98A AU728426B2 (en) | 1997-05-05 | 1998-05-05 | Poly(vinyl alcohol) cryogel |
| DE69828050T DE69828050T2 (en) | 1997-05-05 | 1998-05-05 | A process for producing a polyvinyl alcohol cryogel |
| EP98918953A EP0991402B1 (en) | 1997-05-05 | 1998-05-05 | Process for preparing a poly(vinyl alcohol) cryogel |
| AT98918953T ATE284203T1 (en) | 1997-05-05 | 1998-05-05 | METHOD FOR PRODUCING A POLY(VINYL) ALCOHOL CRYOGEL |
| CA002288793A CA2288793C (en) | 1997-05-05 | 1998-05-05 | Poly(vinyl alcohol) cryogel |
| DK98918953T DK0991402T3 (en) | 1997-05-05 | 1998-05-05 | Process for preparing a poly (vinyl alcohol) cryogel |
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US4587597P | 1997-05-05 | 1997-05-05 | |
| US60/045,875 | 1997-05-05 | ||
| US08/932,029 US5981826A (en) | 1997-05-05 | 1997-09-17 | Poly(vinyl alcohol) cryogel |
| US08/932,029 | 1997-09-17 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| WO1998050017A1 WO1998050017A1 (en) | 1998-11-12 |
| WO1998050017B1 true WO1998050017B1 (en) | 1998-12-10 |
Family
ID=26723293
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/US1998/009129 WO1998050017A1 (en) | 1997-05-05 | 1998-05-05 | Poly(vinyl alcohol) cryogel |
Country Status (11)
| Country | Link |
|---|---|
| US (3) | US5981826A (en) |
| EP (2) | EP0991402B1 (en) |
| JP (2) | JP3506718B2 (en) |
| AT (1) | ATE284203T1 (en) |
| AU (1) | AU728426B2 (en) |
| CA (1) | CA2288793C (en) |
| DE (1) | DE69828050T2 (en) |
| DK (1) | DK0991402T3 (en) |
| ES (1) | ES2232945T3 (en) |
| PT (1) | PT991402E (en) |
| WO (1) | WO1998050017A1 (en) |
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1997
- 1997-09-17 US US08/932,029 patent/US5981826A/en not_active Expired - Lifetime
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1998
- 1998-05-05 ES ES98918953T patent/ES2232945T3/en not_active Expired - Lifetime
- 1998-05-05 PT PT98918953T patent/PT991402E/en unknown
- 1998-05-05 AU AU71766/98A patent/AU728426B2/en not_active Ceased
- 1998-05-05 EP EP98918953A patent/EP0991402B1/en not_active Expired - Lifetime
- 1998-05-05 CA CA002288793A patent/CA2288793C/en not_active Expired - Fee Related
- 1998-05-05 AT AT98918953T patent/ATE284203T1/en not_active IP Right Cessation
- 1998-05-05 WO PCT/US1998/009129 patent/WO1998050017A1/en active IP Right Grant
- 1998-05-05 JP JP54838198A patent/JP3506718B2/en not_active Expired - Lifetime
- 1998-05-05 EP EP04012443A patent/EP1468676A3/en not_active Withdrawn
- 1998-05-05 DE DE69828050T patent/DE69828050T2/en not_active Expired - Lifetime
- 1998-05-05 DK DK98918953T patent/DK0991402T3/en active
-
1999
- 1999-03-17 US US09/271,032 patent/US6231605B1/en not_active Expired - Lifetime
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2001
- 2001-05-01 US US09/846,788 patent/US20010029399A1/en not_active Abandoned
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2002
- 2002-07-22 JP JP2002212822A patent/JP3971260B2/en not_active Expired - Lifetime
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