Three-dimensional polymer matrices

• US 6,471,993 B1
• Filed: 01/28/2000
• Issued: 10/29/2002
• Est. Priority Date: 08/01/1997
• Status: Expired due to Fees

• Current Assignee: All Season Toys, Inc.
• Original Assignee: Massachusetts Institute of Technology
• Inventors: Martin, Ivan, Seidel, Joachim, Langer, Robert S., Shastri, Venkatram R.
• Primary Examiner(s): Page, Thurman K.
• Assistant Examiner(s): DI NOLA BARON, LILIANA
• Application Number:
  US09/463,709
• Time in Patent Office: 1,005 Days
• Field of Search: 424/484, 424/486, 424/487, 424/422, 424/423, 424/424, 424/425, 424/426, 514/772.3
• US Class Current: 424/486
• CPC Class Codes: A61K 35/32 Bones; Osteocytes; Osteoblasts; Tendons; Tenocytes; Teeth; Odontoblasts; Cartilage; Chondrocytes; Synovial membrane
• CPC Class Codes: A61K 38/465 acting on ester bonds (3.1), e.g. lipases, ribonucleases
• CPC Class Codes: A61K 9/1641 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poloxamers
• CPC Class Codes: A61K 9/1647 Polyesters, e.g. poly(lactide-co-glycolide)
• CPC Class Codes: A61L 27/18 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 27/26 Mixtures of macromolecular compounds
• CPC Class Codes: A61L 27/34 Macromolecular materials
• CPC Class Codes: A61L 27/3843 Connective tissue
• CPC Class Codes: A61L 27/3847 Bones
• CPC Class Codes: A61L 27/3882 Hollow organs, e.g. bladder, esophagus, urether, uterus
• CPC Class Codes: A61L 27/56 Porous materials, e.g. foams or sponges
• CPC Class Codes: B33Y 80/00 Products made by additive manufacturing
• 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: C08L 67/04 Polyesters derived from hydroxycarboxylic acids, e.g. lactones C08L67/06 takes precedence
• CPC Class Codes: C12N 2500/38 Vitamins
• CPC Class Codes: C12N 2501/115 Basic fibroblast growth factor (bFGF, FGF-2)
• CPC Class Codes: C12N 2501/39 Steroid hormones
• CPC Class Codes: C12N 2533/40 Polyhydroxyacids, e.g. polymers of glycolic or lactic acid (PGA, PLA, PLGA); Bioresorbable polymers
• CPC Class Codes: C12N 5/0068 General culture methods using substrates for specific animal cell type C12N5/06
• CPC Class Codes: C12N 5/0655 Chondrocytes; Cartilage
• CPC Class Codes: C12Y 301/03001 : Alkaline phosphatase (3.1.3.1)
• CPC Class Codes: G01N 33/545 : Synthetic resin

Abstract

Matrices that include a macrostructure having a semi-solid network and voids, and a microstructure having voids, in which the microstructure is located within the semi-solid network are disclosed. Methods for preparing these matrices are also disclosed.

Claims

1. A matrix comprising a macrostructure having a substantially continuous semi-solid network and voids, said matrix further comprising a microstructure having voids, wherein said microstructure is located within said semi-solid network.

2. The matrix of claim 1, wherein said semi-solid network comprises a polymer.

3. The matrix of claim 1, wherein said matrix comprises a copolymer having a carboxylic acid group or a copolymer having an amine group.

4. The matrix of claim 1, wherein said matrix comprises a conductive polymer selected from the group consisting of polypyrrole, polyaniline, polyacetylene, and polythiophene.

5. The matrix of claim 1, wherein said semi-solid network consists essentially of a polymer or mixture of polymers.

6. The matrix of claim 1, wherein the surface area of said matrix is at least 1 m²/g.

7. The matrix of claim 1, wherein said voids of said macrostructure are substantially continuous.

8. The matrix of claim 1, wherein at least 10% of said voids of said macrostructure and said voids of said microstructure are connected.

9. The matrix of claim 1, wherein said voids of said macrostructure and said voids of said microstructure are not connected.

10. The matrix of claim 1, said voids of said macrostructure defining openings, wherein the average diameter of said openings and the average diameter of the cross-sections of said semi-solid network have a ratio of from 2:

1 to 10;

1.

11. The matrix of claim 10, wherein said ratio is from 2:

1 to 5;

1.

12. The matrix of claim 1, wherein the semi-solid network of a cubic portion of said matrix having dimensions of 0.5 cm on all sides and having voids defining openings having an average diameter of 50-500 μ

m has a connectivity number of at least 10.

13. The matrix of claim 12, wherein said connectivity number is at least 20.

14. The matrix of claim 1, a cross section of said semi-solid network having a maximum and a minimum diameter, wherein the ratio of said maximum diameter and said minimum diameter is from 1:

1 to 10;

1.

15. The matrix of claim 1, wherein at least 10% of the voids of said microstructure have a fractal dimension of at least 3.

16. The matrix of claim 15, wherein less than 10% of the voids of said macrostructure have a fractal dimension higher than 1.

17. The matrix of claim 1, wherein said matrix is three dimensional.

18. The matrix of claim 1, wherein the exterior face of said matrix is porous.

19. The matrix of claim 1, wherein said matrix has a porosity of at least about 20%.

20. The matrix of claim 1, wherein said matrix is biodegradable.

21. The matrix of claim 1, wherein said matrix is bioerodible.

22. The matrix of claim 1, wherein said matrix is bioresorbable.

23. The matrix of claim 1, wherein said matrix is impermeable to cells.

24. The matrix of claim 1, wherein said matrix is permeable to bodily fluids.

25. The matrix of claim 1, wherein said matrix is permeable to cells.

26. The matrix of claim 1, wherein said matrix further comprises a living cell.

27. The matrix of claim 1, wherein said matrix changes in size less than 50% when cells are added to said matrix.

28. The matrix of claim 1, wherein said matrix has a compressive modulus of at least 0.4 MPa at 4% strain.

29. The matrix of claim 1, wherein said matrix has a density of less than about 0.150 g/cc.