Claims
- 1. A cell-regulating, comb-type copolymer comprising:
a) a hydrophobic polymer backbone; b) non-cell binding hydrophilic polymeric side chains grafted to the polymer backbone, wherein the side chains have a molecular weight between 200 and 2000 Daltons; wherein between zero and 100% of the non-cell binding, hydrophilic side chains are end-capped with cell-binding or cell-signaling ligands to form short cell-binding copolymer side chains and wherein the side chains comprise less than 60% of the total copolymer weight.
- 2. The comb copolymer of claim 1 having a total molecular weight of greater than 10,000 Daltons.
- 3. The comb copolymer of claim 1, wherein the backbone is biodegradable.
- 4. The copolymer of claim 1, wherein the backbone is non-biodegradable.
- 5. The copolymer of claim 1 wherein the side chains are less than 500 Daltons and constitute less than 60% of the total copolymer weight.
- 6. The copolymer of claim 1 wherein the mole percentage of backbone segments attached to hydrophilic side chains is between 2 and 30%.
- 7. The copolymer of claim 1 wherein the percent of hydrophilic side chains which include functional groups capable of being covalently or ionically attached to a cell-binding or cell-signaling ligand is between 1 and 20%.
- 8. The copolymer of claim 1, wherein the non-cell binding side chains are selected from the group consisting of polyethylene glycol, polyethylene oxide, polyacrylic acid and dextran.
- 9. The copolymer of claim 1, wherein the ligands are selected from the group consisting of adhesion peptides, cell-signaling peptides and growth factors.
- 10. The copolymer of claim 1 in a mixture further comprising non-cell-binding comb copolymers whose side chains are not end-capped with cell-binding or cell-signaling ligands.
- 11. The comb copolymer mixture of claim 10 wherein less than 20% of the comb copolymers comprise side chains that are end-capped with cell-binding or cell-signaling ligands.
- 12. A tissue engineering matrix, cell culture matrix, biomedical device, or implant formed of or coated with the cell-regulating, comb-type copolymer comprising:
a) a hydrophobic polymer backbone; b) non-cell binding hydrophilic polymeric side chains grafted to the polymer backbone, wherein the side chains have a molecular weight between 200 and 2000 Daltons; wherein between zero and 100% of the non-cell binding, hydrophilic side chains are end-capped with cell-binding or cell-signaling ligands to form short cell-binding copolymer side chains and wherein the side chains comprise less than 60% of the total copolymer weight, wherein the comb copolymer is effective in regulating cellular adhesion or response to the surface.
- 13. The tissue engineering matrix, cell culture matrix, biomedical device or implant of claim 12 seeded with cells selected from the group consisting of parenchymal cells, skin cells, muscle cells, cartilage cells, nerve cells and bone cells.
- 14. The tissue engineering matrix, cell culture matrix, biomedical device or implant of claim 12 wherein the cell-regulating, comb-type copolymer comprises defined mixtures of non-cell binding and ligand-modified cell-regulating, comb-type copolymers.
- 15. The tissue engineering matrix, cell culture matrix, biomedical device or implan of claim 14, wherein the surface presents discrete nanodomains or clusters of a single ligand type against a background of non-cell binding hydrophilic side chains.
- 16. The tissue engineering matrix, cell culture matrix, biomedical device or implant of claim 15, wherein each nanodomain or cluster contains between 2 and 50 cell-signaling ligands in an area of 0.0001-0.01 microns square, with the overall spacing between the edges of such domains in the range 3-200 nm.
- 17. The tissue engineering matrix, cell culture matrix, biomedical device or implant of claim 14, wherein the surface presents discrete nanodomains or clusters of two or more ligand types against a background of non-cell binding hydrophilic side chains.
- 18. The tissue engineering matrix, cell culture matrix, biomedical device or implant of claim 17, wherein each nanodomain or cluster contains between 2 and 50 cell-signaling ligands in an area of 0.0001-0.01 microns square, with the overall spacing between the edges of such domains in the range 3-200 nm.
- 19. A method for making a tissue engineering matrix, cell culture matrix, implant or biomedical device with regulated cellular adhesion or response comprising coating or forming the matrix, implant or device with a comb copolymer comprising:
a) a hydrophobic polymer backbone; b) non-cell binding hydrophilic polymeric side chains grafted to the polymer backbone, wherein the side chains have a molecular weight between 200 and 2000 Daltons; wherein between zero and 100% of the non-cell binding, hydrophilic side chains are end-capped with cell-binding or cell-signaling ligands to form short cell-binding copolymer side chains and wherein the side chains comprise less than 60% of the total copolymer weight.
- 20. The method of making a tissue engineering matrix, cell culture matrix, biomedical device or implant of claim 19 in which non-cell binding side chains of the comb copolymers at the surface are end-capped with ligands after the coating, matrix, device or implant is formed.
- 21. A method for engineering tissue comprising growing cells on a tissue-engineering matrix formed of or coated with the cell-regulating, comb-type copolymer comprising:
a) a hydrophobic polymer backbone; b) non-cell binding hydrophilic polymeric side chains grafted to the polymer backbone, wherein the side chains have a molecular weight between 200 and 2000 Daltons; wherein between zero and 100% of the non-cell binding, hydrophilic side chains are end-capped with cell-binding or cell-signaling ligands to form short cell-binding copolymer side chains and wherein the side chains comprise less than 60% of the total copolymer weight, wherein the comb copolymer is effective in regulating cellular adhesion or response to the surface.
- 22. A polymer latex comprising polymer particles dispersed in aqueous-containing media stabilized by cell-regulating, comb-type copolymer comprising:
a) a hydrophobic polymer backbone; b) non-cell binding hydrophilic polymeric side chains grafted to the polymer backbone, wherein the side chains have a molecular weight between 200 and 2000 Daltons; wherein between zero and 100% of the non-cell binding, hydrophilic side chains are end-capped with cell-binding or cell-signaling ligands to form short cell-binding copolymer side chains and wherein the side chains comprise less than 60% of the total copolymer weight.
- 23. The polymer latex of claim 22 wherein the comb copolymers serve as a stabilizing agent during the latex synthesis.
- 24. The polymer latex of claim 22 whereby the comb copolymer comprises less than 1% of the latex dry weight.
- 25. The polymer latex of claim 22 further comprising non-cell-binding comb copolymers whose side chains are not end-capped with cell-binding or cell-signaling ligands.
- 26. The polymer latex of claim 22 further comprising latex particles stabilized by non-cell binding comb copolymers to achieve a defined mixture of non-cell binding and ligand-modified cell-regulating latex particles.
- 27. The polymer latex of claim 22 in which non-cell binding side chains of the comb copolymers at the surface of the particles are end-capped with ligands after the latex particles are synthesized.
- 28. Polymer coatings and films that regulate cell behavior prepared by casting a polymer latex comprising polymer particles dispersed in aqueous-containing media stabilized by cell-regulating, comb-type copolymers comprising:
a) a hydrophobic polymer backbone; b) non-cell binding hydrophilic polymeric side chains grafted to the polymer backbone, wherein the side chains have a molecular weight between 200 and 2000 Daltons; wherein between zero and 100% of the non-cell binding, hydrophilic side chains are end-capped with cell-binding or cell-signaling ligands to form short cell-binding copolymer side chains and wherein the side chains comprise less than 60% of the total copolymer weight.
- 29. The polymer films and coatings of claim 28 prepared by casting a mixed latex of microparticles stabilized with the non-cell binding comb copolymers to achieve a defined mixture of non-cell binding and ligand-modified cell-regulating latex particles.
- 30. The polymer films and coatings of claim 28 comprising discrete domains of a single type of cell-signaling ligand against a background of non-cell binding hydrophilic side chains, where the domain size is on the order of the latex particles.
- 31. The polymer films and coatings of claim 30 wherein the domain size is between 0.1 and 10 microns in diameter.
- 32. The polymer films and coatings of claim 28 comprising discrete domains of multiple cell-signaling ligands against a background of non-cell binding hydrophilic side chains, wherein the domain size is on the order of the latex particles.
- 33. The polymer films and coatings of claim 32 where the domain size is between 0.1 and 10 microns in diameter.
- 34. The polymer film or coating of claim 28 in which non-cell binding side chains of the comb copolymers at the surface of the applied film or coating are end-capped with ligands after the coating or film is prepared.
- 35. A method of making polymer coatings and films that regulate cell behavior comprising casting a polymer latex comprising polymer particles dispersed in aqueous-containing media stabilized by cell-regulating, combtype copolymers comprising:
a) a hydrophobic polymer backbone; b) non-cell binding hydrophilic polymeric side chains grafted to the polymer backbone, wherein the side chains have a molecular weight between 200 and 2000 Daltons; wherein between zero and 100% of the non-cell binding, hydrophilic side chains are end-capped with cell-binding or cell-signaling ligands to form short cell-binding copolymer side chains and wherein the side chains comprise less than 60% of the total copolymer weight.
- 36. The method of making polymer film or coatings of claim 35 wherein non-cell binding side chains of the comb copolymers at the surface are end-capped with ligands after the coating or film is prepared.
Parent Case Info
[0001] This application claims priority to U.S. Ser. No. 60/081,596 filed Apr. 13, 1998.
Government Interests
[0002] The United States government has certain rights in this invention by virtue of National Science Foundation grant No. DMR-9400334, OSP Project No. 6227 to Anne M. Mayes, and National Science Foundation Grant No. BES 9632714 to L. G. Griffith.
Provisional Applications (1)
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Number |
Date |
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60081596 |
Apr 1998 |
US |
Divisions (1)
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Number |
Date |
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Parent |
09290140 |
Apr 1999 |
US |
Child |
09634095 |
Aug 2000 |
US |
Continuations (1)
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Number |
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09634095 |
Aug 2000 |
US |
Child |
09817887 |
Mar 2001 |
US |