Open pore biodegradable matrices

• US 6,281,256 B1
• Filed: 06/06/2000
• Issued: 08/28/2001
• Est. Priority Date: 03/31/1997
• Status: Expired due to Term

• Current Assignee: Board of Regents of the University of Michigan (University of Michigan)
• Original Assignee: Board of Regents of the University of Michigan (University of Michigan)
• Inventors: Mooney, David J., Shea, Lonnie, Harris, Leatrese
• Primary Examiner(s): COONEY, JOHN M
• Application Number:
  US09/402,119
• Time in Patent Office: 448 Days
• Field of Search: 521/61, 521/63, 521/149, 521/182, 521/51, 521/123, 521/183, 521/189
• US Class Current: 521/51
• CPC Class Codes: A61K 9/204 Polyesters, e.g. poly(lactide-co-glycolide)
• CPC Class Codes: B29C 44/3446 Feeding the blowing agent
• CPC Class Codes: B29C 67/202 comprising elimination of a solid or a liquid ingredient
• CPC Class Codes: C08J 2201/032 Impregnation of a formed object with a gas expandable particles, e.g. polystyrene beads C08J9/18
• CPC Class Codes: C08J 2201/0446 Elimination of NaCl only
• CPC Class Codes: C08J 2203/06 CO2, N2 or noble gases
• CPC Class Codes: C08J 2205/05 Open cells, i.e. more than 50% of the pores are open
• CPC Class Codes: C08J 2367/02 Polyesters derived from dicarboxylic acids and dihydroxy compounds; C08J2367/06 takes precedence
• CPC Class Codes: C08J 2367/04 Polyesters derived from hydroxy carboxylic acids, e.g. lactones C08J2367/06 takes precedence
• CPC Class Codes: C08J 9/122 Hydrogen, oxygen, CO2, nitrogen or noble gases
• CPC Class Codes: C08J 9/18 by impregnating polymer particles with the blowing agent
• CPC Class Codes: C08J 9/26 by elimination of a solid phase from a macromolecular composition or article, e.g. leaching out

Abstract

The invention is directed to a process for preparing porous polymer materials by a combination of gas forming and particulate leaching steps. The invention is also directed to porous polymer material prepared by the process, particularly having a characteristic interconnected pore structure, and to methods for using such porous polymer material, particularly for tissue engineering.

Claims

1. A process for preparing a porous polymer material which comprises forming pores in a polymer material which contains a leachable particulate by foaming and subsequently leaching out the particulate material to form additional porosity wherein the polymer material comprises a homopolymer of a lactic acid or glycolic acid, a copolymer of a lactic acid and glycolic acid, an aliphatic polyester, a polyanhydride, a polyphosphazine, a polypeptide, a blend of a copolymer of a lactic acid and glycolic acid with an alginate, or any combination of the above materials.

2. The process of claim 1, wherein formation of the pores by gas foaming is conducted by subjecting a mixture of particles of the polymer and particles of the particulate to an elevated pressure atmosphere of an inert gas such that the gas dissolves into the polymer and then creating a thermodynamic instability such that nucleation and growth of gas pores occurs and the polymer containing the particulate forms a continuous matrix.

3. The process of claim 2, wherein the mixture of particles of the polymer and particles of the particulate is compression molded into a selected size and shape before formation of the gas pores.

4. The process of claim 2, wherein the thermodynamic instability is created by reduction of the pressure atmosphere.

5. The process of claim 2, wherein the gas is CO₂.

6. The process of claim 1, wherein the polymer is a biocompatible polymer.

7. The process of claim 1, wherein the polymer is a biocompatible and biodegradable polymer.

8. The process of claim 1, wherein the polymer is a homopolymer or copolymer of lactic acid and/or glycolic acid.

9. The process of claim 1, wherein the polymer is PLGA.

10. The process of claim 1, wherein the polymer is a blend of a homopolymer or copolymer of lactic acid and/or glycolic acid with another polymer.

11. The process of claim 10, wherein the polymer is a blend of a homopolymer or copolymer of lactic acid and/or glycolic acid with an alginate polymer.

12. The process of claim 1, wherein the particulate is a water-soluble particulate.

13. The process of claim 1, wherein the particulate is a salt.

14. The process of claim 1, wherein the particulate is NaCl.

15. The process of claim 1, wherein the size and amount of the particulate is selected such that an interconnected pore structure in the porous polymer material is formed.

16. The process of claim 13, wherein the amount of particulate is at least 50% by volume of the mixture of particles of the polymer and particles of the particulate.

17. The process of claim 13, wherein the average particle size of the particulate is from 10 to 500 microns.

18. A porous polymer comprising a polymer matrix containing pores formed by gas foaming and pores formed by leaching out of a particulate from the polymer wherein the polymer material comprises a homopolymer of a lactic acid or glycolic acid, a copolymer of a lactic acid and glycolic acid, an aliphatic polyester, a polyanhydride, a polyphosphazine, a polypeptide, a blend of a copolymer of a lactic acid and glycolic acid with an alginate, or any combination of the above materials.

19. The polymer of claim 18, wherein the polymer matrix is a biocompatible and biodegradable polymer.

20. The polymer of claim 18, wherein the polymer matrix is a homopolymer or copolymer of lactic acid and/or glycolic acid.

21. The polymer of claim 18, wherein the polymer matrix is PLGA.

22. The polymer of claim 18, wherein the polymer has an interconnected pore structure.

23. The polymer of claim 18, wherein the combination of pores provides a uniform open pore structure.

24. The polymer of claim 18, wherein the polymer exhibits a tensile modulus of 850 kPa or higher.

25. A method for drug delivery which comprises introducing a drug contained within a porous polymer of claim 18.

26. A method for drug delivery according to claim 25, wherein the drug is a growth factor contained within the polymeric structure of a polymer bead which is contained within the porous polymer.

27. A method for tissue engineering which comprises introducing as a matrix for the tissue a porous polymer of claim 18.

28. A method for cell transplantation comprising administering a combination of a porous polymer of claim 18 and cells for transplantation.

29. A method for cell culturing which comprises culturing cells in the pores of a porous polymer of claim 18.

34. The polymer of claim 18, which further comprises a drug contained within the pores of the porous polymer.

35. The polymer of claim 18, which further comprises viable cells within the pores of the porous polymer.

36. The polymer material of claim 28, which further comprises within the pores of the section of porous polymer viable cells for tissue regeneration.

30. A polymer material which comprises a section of porous polymer comprising a polymer matrix containing pores formed by gas foaming and pores formed by leaching out of a particulate from the polymer and a section of impermeable polymer integrally connected wherein the polymer material comprises a homopolymer of a lactic acid or glycolic acid, a copolymer of a lactic acid and glycolic acid, an aliphatic polyester, a polyanhydride, a polyphosphazine, a polypeptide, a blend of a copolymer of a lactic acid and glycolic acid with an alginate, or any combination of the above materials.

31. The polymer material of claim 30, wherein the porous polymer has a uniform open pore structure and the impermeable polymer is of the same polymer material but without an open pore structure.

32. A method for guided tissue regeneration which comprises introducing to the location requiring tissue regeneration a polymer material according to claim 30.

33. The polymer material of claim 30, wherein the porous polymer and the impermeable polymer are of different polymer material.