Tissue engineering scaffolds

• US 20040026811A1
• Filed: 12/27/2002
• Published: 02/12/2004
• Est. Priority Date: 01/02/2002
• Status: Active Grant

• 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: Murphy, William L., Mooney, David J., Dennis, Robert G.
• Granted Patent: US 7,575,759 B2
• Time in Patent Office: Days
• US Class Current: 264/41
• CPC Class Codes: A61L 27/18 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 27/38 containing added animal cells organs or tissue containing native cells A61L27/36
• CPC Class Codes: A61L 27/56 Porous materials, e.g. foams or sponges
• CPC Class Codes: A61L 31/06 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds A61L31/041 takes precedence
• CPC Class Codes: A61L 31/146 Porous materials, e.g. foams or sponges
• CPC Class Codes: C08L 67/04 Polyesters derived from hydroxycarboxylic acids, e.g. lactones C08L67/06 takes precedence

Abstract

The present invention relates to methods and compositions for the production of scaffolds, such scaffolds to be used for a variety of purposes, including tissue engineering. More specifically, the present invention relates to the use of fused crystals, such as fused salt crystals to form a framework. The methods for producing the scaffolds of this invention improve the porosity, interconnectivity and ease of manufacture as compared to prior art methods.

Claims

1. A method, comprising;

a) providing i) a plurality of particles, said particles comprising a porogen and ii) a solution comprising a polymer;

b) exposing said particles to conditions so that said porogen fuses together to produce a framework comprising a frame and free space between said fused porogen;

c) contacting said framework with said solution under conditions such that said solution substantially fills said free space;

d) treating said solution such that said polymer forms a scaffold; and

e) removing said fused porogen from said scaffold.

2. The method of claim 1, wherein greater than 75% of the free space is filled in step (c).

3. The method of claim 1, wherein said porogen is comprised of salt crystals.

4. The method of claim 3, wherein said salt crystals are selected from the group consisting of calcium chloride, sodium chloride, sodium phosphate, potassium chloride, potassium phosphate, calcium phosphate and magnesium chloride.

5. The method of claim 1, wherein said polymer in said polymer solution is selected from the group consisting of a polyester, a poly(alpha-hydroxy ester), a polyether, a polystyrene and polymethylmethacrylate.

6. The method of claim 5, wherein said polyester is poly(lactide-co-glycolide).

7. The method of claim 5, wherein said polyether is polyethylene oxide or polyethylene glycol.

8. The method of claim 1, wherein said treating of step (d) comprises evaporating the polymer solvent.

9. The method of claim 1, wherein said removing of step (e) comprises dissolving said fused salt crystals.

10. The method of claim 1, wherein said conditions of step (b) comprise exposing said salt crystals to between approximately 90% and approximately 100% relative humidity for approximately 8 to approximately 28 hours.

11. The method of claim 1, wherein said scaffold after step (e) comprises cells.

12. A method, comprising;

a) providing i) a plurality of particles, said particles comprising a porogen and ii) a solution comprising a biocompatible polymer;

b) exposing said particles to humidity such that said porogen fuses together to produce a framework comprising a frame and free space between said fused porogen;

c) contacting said framework with said solution under conditions such that said solution substantially fills said free space;

d) treating said solution such that said polymer forms a scaffold; and

e) removing said fused porogen from said scaffold.

13. The method of claim 12, wherein greater than 75% of the free space is filled in step (c).

14. The method of claim 12, wherein said porogen comprises slat crystals.

15. The method of claim 14, wherein said salt crystals are selected from the group consisting of calcium chloride, sodium chloride, sodium phosphate, potassium chloride, potassium phosphate, calcium phosphate and magnesium chloride.

16. The method of claim 12, wherein said polymer in said polymer solution is selected from the group consisting of a polyester, a poly(alpha-hydroxy ester), a polyether, a polystyrene and polymethylmethacrylate.

17. The method of claim 16, wherein said polyester is poly(lactide-co-glycolide).

18. The method of claim 16, wherein said polyether is polyethylene oxide or polyethylene glycol.

19. The method of claim 12, wherein said treating of step (d) comprises evaporating the polymer solvent.

20. The method of claim 12, wherein said removing of step (e) comprises dissolving said fused salt crystals.

21. The method of claim 12, wherein said conditions of step (b) comprise exposing said salt crystals to between approximately 90% and approximately 100% relative humidity for approximately 8 to approximately 28 hours.

22. The method of claim 12, wherein said scaffold after step (e) comprises cells.

23. The method of claim 12, wherein said step b) additionally comprises exposing said porogen to positive pressure such that said free space between said fused porogen is controlled.

24. A method, comprising;

a) providing i) a plurality of particles, said particles comprising a porogen and ii) a solution comprising a polymer;

b) exposing said particles to conditions so that said porogen fuses together to produce a framework comprising a frame and free space between said fused porogen;

c) contacting said framework with said solution under conditions such that said solution substantially fills said free space;

d) compressing said framework and solution such that a solid substance is formed;

e) exposing said solid substance to high pressure gas;

f) decreasing gas pressure to ambient pressure; and

g) removing said fused porogen from said scaffold.

25. The method of claim 24, wherein said compression is between 100 and 2000 psi.

26. The method of claim 24, wherein said gas pressure is between 400 and 1200 psi.

27. The method of claim 24, wherein said solid substance is a semi-solid.