Biodegradable foams for cell transplantation

• US 5,686,091 A
• Filed: 03/28/1994
• Issued: 11/11/1997
• Est. Priority Date: 03/28/1994
• Status: Expired due to Term

• Current Assignee: Johns Hopkins University
• Original Assignee: Johns Hopkins University
• Inventors: Leong, Kam W., Kadiyala, Sudhakar, Lo, Hungnan
• Primary Examiner(s): KRASS, FREDERICK F
• Application Number:
  US08/219,017
• Time in Patent Office: 1,324 Days
• Field of Search: 264/45.6, 264/45.8, 264/45.9, 264/46.4, 264/46.6, 264/46.8, 264/48, 264/53, 264/41, 435/246, 424/426, 428/306.6, 428/308.4, 428/315.5, 623/16
• US Class Current: 424/426
• CPC Class Codes: A61F 2/022 Artificial gland structures using bioreactors hemodialysis A61M1/16; hemofiltration A61M1/34; other extracorporeal blood treatment A61M1/36
• CPC Class Codes: Y10T 428/249955 Void-containing component partially impregnated with adjacent component
• CPC Class Codes: Y10T 428/249958 Void-containing component is synthetic resin or natural rubbers
• CPC Class Codes: Y10T 428/249978 Voids specified as micro

Abstract

A structurally rigid biodegradable foam scaffold useful for cell transplantation is provided. The foam can be loaded with nutrients and/or drugs that elute from the foam during transplant to promote growth of the cells. The foam, which features a continuous network of pores, is fabricated using a novel method involving phase separation and consequent expansion upon sublimation of a liquid solvent, preferably naphthalene.

Claims

1. A method for producing a biocompatible and biodegradable porous foam comprising:

a) dissolving from about 0.5 to 10 weight percent of a biocompatible polymer in a liquid solvent having a melting point in the range from about 30°

to about 90°

C. to form a polymer solution;

b) placing the solvent solution onto a form under conditions promoting spinodal decomposition in the solution;

c) quenching the polymer solution in the form;

d) sublimating the solvent in the solution; and

e) obtaining a biocompatible porous foam comprising a substantially continuous polymer phase and a substantially continuous gas phase with substantially uniform pore size and pore distribution and having an average pore size in the range from about 20 to 500 μ

m, in diameter.

2. The method of claim 1 wherein the solvent is naphthalene.

3. The method of claim 1 wherein the placing is by spraying the polymer solution onto the form in layers.

4. The method of claim 1 wherein the form is a mold.

5. The method of claim 4 wherein the mold is in the shape of a bone.

6. The method of claim 1 wherein from about 1 to 10 weight percent of a cell growth nutrient is added to the polymer solution in step a).

7. The method of claim 6 wherein the nutrient is selected from the group consisting of enzymes, bone morphogenetic proteins (BMP), epidermal growth factor (EGF), fibroblast growth factor (FGF), platelet-derived growth factor (PDGF), insulin-like growth factor (IGF-I and -II), TGF-β

, and dexamethason.

8. The method of claim 1 wherein the polymer comprises polylactic acid.

9. The method of claim 8 wherein the pore surface area is from about 1.2905 to 0.79 m² /g, the pore volume is from about 17.747 to 7.198 cm³ /g, and the porosity is from about 87 to 71 percent.

10. The method of claim 9 wherein the polymer solution is quenched while in the early stages of spinodal decomposition.

11. The method of claim 1 wherein the polymer is a polyphosphoester.

12. The method of claim 1 further comprising adding a therapeutic amount of a drug to the polymer solution in step a).

13. The method of claim 12 wherein the polymer solution is quenched while in the early stages of spinodal decomposition.

23. The method of claim 1 including adding a cell growth nutrient to the polymer solution while forming the polymer solution.

24. The method of claim 1 wherein the polymer comprises a co-polymer.

14. A three dimensional biocompatible and biodegradable porous foam comprising a substantially continuous polymer phase and a substantially continuous gas phase with substantially uniform pore size and pore distribution and having an average pore size in the range from about 20 to 500 μ

m; and

cultured tissue cells contained within the pores.

15. The porous foam of claim 14 wherein the polymer phase comprises polylactic acid.

16. The porous foam of claim 15 wherein the pore surface area is from about 1.2905 to 0.79 m² /g, the pore volume is from about 17.747 to 7.198 cm³ /g, and the porosity is from about 87 to 71 percent.

17. The porous foam of claim 15 wherein the polymer phase further comprises a cell nutrient.

18. The porous foam of claim 15 wherein the polymer phase further comprises a therapeutic amount of a drug.

19. The porous foam of claim 14 wherein the density of the cultured tissue cells is about 10⁴ cells/ml of culture.

20. A biodegradable and biocompatible porous foam comprising a substantially continuous polymer phase and a substantially continuous gas phase with substantially uniform pore size and pore distribution, said foam also including a cell growth nutrient.

21. The porous foam according to claim 20 including cultured tissue cells in the pores.

22. The porous foam according to claim 20 including at least one drug.