Reverse fabrication of porous materials

• US 6,673,285 B2
• Filed: 05/11/2001
• Issued: 01/06/2004
• Est. Priority Date: 05/12/2000
• Status: Expired due to Fees

• 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: Ma, Peter X.
• Primary Examiner(s): Kuhns, Allan R.
• Application Number:
  US09/853,478
• Publication Number:
  US 20020005600A1
• Time in Patent Office: 970 Days
• Field of Search: 264/49, 264/219, 264/317, 521/61, 295/271
• US Class Current: 264/49
• CPC Class Codes: B01J 20/261 obtained by reactions only involving carbon to carbon unsaturated bonds macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds per se C08F
• CPC Class Codes: B01J 20/262 obtained otherwise than by reactions only involving carbon to carbon unsaturated bonds, e.g. obtained by polycondensation macromolecular compounds obtained otherwise than by reactions only involving unsaturated carbon-to-carbon bonds per se C08G
• CPC Class Codes: B01J 20/264 derived from different types of monomers, e.g. linear or branched copolymers, block copolymers, graft copolymers
• CPC Class Codes: B01J 20/28045 Honeycomb or cellular structures; Solid foams or sponges
• CPC Class Codes: B01J 20/285 based on polymers
• CPC Class Codes: B01J 20/30 Processes for preparing, regenerating, or reactivating
• CPC Class Codes: B01J 20/305 Addition of material, later completely removed, e.g. as result of heat treatment, leaching or washing, e.g. for forming pores
• CPC Class Codes: B01J 2220/54 Sorbents specially adapted for analytical or investigative chromatography
• CPC Class Codes: B29C 67/20 for porous or cellular articles, e.g. of foam plastics, coarse-pored chemical aspects of working up macro-molecular substances to porous or cellular articles C08J9/00
• CPC Class Codes: B29C 67/202 comprising elimination of a solid or a liquid ingredient
• CPC Class Codes: C08J 9/26 by elimination of a solid phase from a macromolecular composition or article, e.g. leaching out
• CPC Class Codes: Y10T 29/4998 Combined manufacture including applying or shaping of fluent material

Abstract

3-D biodegradable porous, polymer (natural or synthetic) scaffolds with well-controlled, interconnected pores, and method for forming the porous materials. Hydrophilic and/or hydrophobic porogen materials were fabricated into 3-D negative replicas of the desired macroporous architectures. Biodegradable polymers (PLLA and PLGA) were dissolved in a solvent and cast onto the negative replica. After dissolving/leaching out the porogen materials, a porous polymer scaffold was formed. The skeletal structure of PLLA foams consisted of small platelets or nano-fibers, while PLGA foams had homogeneous skeletal structure. To improve the cell seeding, distribution, mass transport, and new tissue organization and vascularization, 3-D macroporous architectures are built in the nano-fibrous matrices. The method tailors polymer scaffolds for a variety of potential tissue engineering applications due to the well-controlled architecture, inter-pore connectivity, and mechanical properties.

Claims

1. A method for forming a porous material, the method comprising the steps of:

casting a natural or synthetic composition onto a negative replica of a desired macroporous architecture of the porous material, thereby forming a body, shaped porogen materials having been assembled into a predesigned three-dimensional configuration, wherein the predesigned three-dimensional configuration is the negative replica; and

removing the porogen materials from the body, thereby forming the porous material having the desired macroporous architecture.

2. The method as defined in claim 1 wherein the method is a continuous process.

3. The method as defined in claim 1 wherein the method is a batch process.

4. The method as defined in claim 1 wherein the natural or synthetic composition includes a liquid.

5. The method as defined in claim 4 wherein the natural or synthetic composition when cast is at least one of a solution, a melt, a slurry, flowable powders, flowable pastes, and mixtures thereof.

6. The method as defined in claim 4 wherein the liquid is a solvent, and wherein the natural or synthetic composition further comprises a polymeric composition.

7. The method as defined in claim 3 wherein, before the casting step, the method further comprises the step of forming the porogen material into at least one predetermined shape.

8. The method as defined in claim 1 wherein the porogen material is selected from the group consisting of salts, sodium hydroxide, sugars, waxes, gelatins, naphthalene, natural or synthetic water soluble polymers, natural or synthetic non-water soluble polymers, degradable polymers, non-degradable polymers, partially degradable polymers, and mixtures thereof.

9. The method as defined in claim 8 wherein the porogen material is a salt selected from the group consisting of sodium chloride, potassium chloride, sodium fluoride, potassium fluoride, sodium iodide, sodium nitrate, sodium sulfate, sodium iodate, and mixtures thereof.

10. The method as defined in claim 8 wherein the porogen material is a sugar selected from the group consisting of saccharin, glucose, fructose, water soluble sugars, and mixtures thereof.

11. The method as defined in claim 8 wherein the porogen material is a wax selected from the group consisting of paraffin, beeswax, and mixtures thereof.

12. The method as defined in claim 1 wherein the shaped porogen materials have at least one predetermined shape selected from the group consisting of cubic or other geometrically shaped crystals, spheres, fibers, discs, regular geometric shapes, irregular geometric shapes, and mixtures thereof.

13. The method as defined in claim 1 wherein the natural or synthetic composition is selected from materials which retain their cast shape during the porogen material removing step.

14. The method as defined in claim 13 wherein the natural or synthetic composition comprises a material selected from the group consisting of ceramics, glass, inorganic compounds, and mixtures thereof.

15. The method as defined in claim 13 wherein the natural or synthetic composition is a polymeric composition.

16. The method as defined in claim 15 wherein the polymeric composition is selected from the group consisting of natural or synthetic hydrophilic polymers, natural or synthetic hydrophobic polymers, natural or synthetic amphophilic polymers, degradable polymers, non-degradable polymers, partially degradable polymers, proteins, artificial proteins, and mixtures thereof.

17. The method as defined in claim 16 wherein the polymeric composition is selected from the group consisting of poly(lactide-co-glycolide) (PLGA), poly(lactide) (PLLA), polyglycolic acid (PGA), polyanhydrides, poly(ortho ethers), polycaprolactone, polyethylene glycol (PEG), polyurethane, copolymers thereof, and mixtures thereof.

18. The method as defined in claim 16 wherein the natural or synthetic hydrophilic polymers are selected from the group consisting of polyacrylic acid, polyvinyl alcohol, polyethylene oxide, polyethylene glycol, polymethacrylic acid (PMAA), alginates, collagens, gelatins, hyaluronic acid, and mixtures thereof.

19. The method as defined in claim 16 wherein the natural or synthetic hydrophobic polymers are selected from the group consisting of poly(methyl methacrylate) (PMMA), polycarbonate, polypropylene oxide (PPO), polyamides, polyvinylidene fluoride (PVDF), polybutylene, polyacrylonitrile, and mixtures thereof.

20. The method as defined in claim 1, further comprising the step of adding functional or inert additives to the porous material.

21. The method as defined in claim 20 wherein the additives are selected from the group consisting of inorganic salts, minerals, drugs, peptides, and mixtures thereof.

22. A method for forming a porous material, the method comprising the steps of:

forming a porogen material into at least one predetermined shape;

assembling a plurality of the shaped porogen materials into a predesigned three-dimensional configuration, wherein the three-dimensional configuration is a negative replica of a desired macroporous architecture of the porous polymeric material;

casting a natural or synthetic composition onto the negative replica, thereby forming a body; and

removing the porogen materials from the body, thereby forming the porous material having the desired macroporous architecture.

23. The method as defined in claim 22 wherein the porogen material is selected from the group consisting of salts, sodium hydroxide, sugars, waxes, gelatins, naphthalene, natural or synthetic water soluble polymers, natural or synthetic non-water soluble polymers, degradable polymers, non-degradable polymers, partially degradable polymers, and mixtures thereof.

24. The method as defined in claim 23 wherein the porogen material is a salt selected from the group consisting of sodium chloride, potassium chloride, sodium fluoride, potassium fluoride, sodium iodide, sodium nitrate, sodium sulfate, sodium iodate, and mixtures thereof.

25. The method as defined in claim 23 wherein the porogen material is a sugar selected from the group consisting of saccharin, glucose, fructose, water soluble sugars, and mixtures thereof.

26. The method as defined in claim 23 wherein the porogen material is a wax selected from the group consisting of paraffin, beeswax, and mixtures thereof.

27. The method as defined in claim 22 wherein the at least one predetermined shape is selected from the group consisting of cubic or other geometrically shaped crystals, spheres, fibers, discs, regular geometric shapes, irregular geometric shapes, and mixtures thereof.

28. The method as defined in claim 22 wherein the natural or synthetic composition is selected from materials which retain their cast shape during the porogen material removing step.

29. The method as defined in claim 28 wherein the natural or synthetic composition is a polymeric composition.

30. The method as defined in claim 29 wherein the polymeric composition is selected from the group consisting of natural or synthetic hydrophilic polymers, natural or synthetic hydrophobic polymers, natural or synthetic amphophilic polymers, degradable polymers, non-degradable polymers, partially degradable polymers, proteins, artificial proteins, and mixtures thereof.

31. The method as defined in claim 30 wherein the polymeric composition is selected from the group consisting of poly(lactide-co-glycolide) (PLGA), poly(lactide) (PLLA), polyglycolic acid (PGA), polyanhydrides, poly(ortho ethers), polycaprolactone, polyethylene glycol (PEG), polyurethane, copolymers thereof, and mixtures thereof.

32. The method as defined in claim 30 wherein the natural or synthetic hydrophilic polymers are selected from the group consisting of polyacrylic acid, polyvinyl alcohol, polyethylene oxide, polyethylene glycol, polymethacrylic acid (PMAA), alginates, collagens, gelatins, hyaluronic acid, and mixtures thereof.

33. The method as defined in claim 30 wherein the natural or synthetic hydrophobic polymers are selected from the group consisting of poly(methyl methacrylate) (PMMA), polycarbonate, polypropylene oxide (PPO), polyamides, polyvinylidene fluoride (PVDF), polybutylene, polyacrylonitrile, and mixtures thereof.

34. The method defined in claim 22, further comprising the step of adding functional or inert additives to the porous material.

35. The method as defined in claim 34 wherein the additives are selected from the group consisting of inorganic salts, minerals, drugs, peptides, and mixtures thereof.

36. A method for forming a porous material, the method comprising the steps of:

casting a natural or synthetic composition onto a negative replica of a desired macroporous architecture of the porous material, thereby forming a body, the negative replica having been formed from a predetermined three-dimensional configuration of shaped porogen materials; and

removing the porogen materials from the body, thereby forming the porous material having the desired macroporous architecture;

wherein the natural or synthetic composition is a polymeric composition selected from materials which retain their cast shape during the porogen material removing step, and wherein the polymeric composition is selected from the group consisting of degradable polymers, and mixtures thereof; and

wherein the degradable polymers are selected from the group consisting of polyamino acids.

37. A method for forming a porous material, the method comprising the steps of:

forming a porogen material into at least one predetermined shape;

combining a plurality of the shaped porogen materials into a predetermined three-dimensional configuration, wherein the three-dimensional configuration is a negative replica of a desired macroporous architecture of the porous polymeric material;

casting a natural or synthetic composition onto the negative replica, thereby forming a body; and

removing the porogen materials from the body, thereby forming the porous material having the desired macroporous architecture;

wherein the natural or synthetic composition is a polymeric composition selected from materials which retain their cast shape during the porogen material removing step, and wherein the polymeric composition is selected from the group consisting of degradable polymers, and mixtures thereof; and

wherein the degradable polymers are selected from the group consisting of polyamino acids.