Porous biodegradable polymeric materials for cell transplantation

• US 20060141000A1
• Filed: 02/10/2004
• Published: 06/29/2006
• Est. Priority Date: 02/01/1993
• Status: Active Grant

• Current Assignee: Children's Medical Center Corporation
• Original Assignee: Massachusetts Institute of Technology
• Inventors: Langer, Robert S., Vacanti, Joseph P., Ingber, Donald E., Mikos, Antonios G.
• Granted Patent: US 7,462,471 B2
• Time in Patent Office: Days
• US Class Current: 424/422
• CPC Class Codes: A61L 2400/06 Flowable or injectable implant compositions
• CPC Class Codes: A61L 27/18 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 27/56 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
• CPC Class Codes: G02B 27/0031 for scanning purposes
• CPC Class Codes: G03F 7/40 Treatment after imagewise removal, e.g. baking
• CPC Class Codes: H01L 21/0273 characterised by the treatment of photoresist layers
• CPC Class Codes: H01L 21/32139 using masks

Abstract

Polymeric materials are used to make a pliable, non-toxic, injectable porous template for vascular ingrowth. The pore size, usually between approximately 100 and 300 microns, allows vascular and connective tissue ingrowth throughout approximately 10 to 90% of the matrix following implantation, and the injection of cells uniformly throughout the implanted matrix without damage to the cells or patient. The introduced cells attach to the connective tissue within the matrix and are fed by the blood vessels. The preferred material for forming the matrix or support structure is a biocompatible synthetic polymer which degrades in a controlled manner by hydrolysis into harmless metabolites, for example, polyglycolic acid, polylactic acid, polyorthoester, polyanhydride, or copolymers thereof. The rate of tissue ingrowth increases as the porosity and/or the pore size of the implanted devices increases. The time required for the tissue to fill the device depends on the polymer crystallinity and is less for amorphous polymers versus semicrystalline polymers. The vascularity of the advancing tissue is consistent with time and independent of the biomaterial composition and morphology.

Claims

1. A polymeric matrix which can be implanted into the body, vascularized and used as a means to achieve a high survival rate for dissociated cells injected into the matrix, wherein the matrix is formed of a biodegradable, biocompatible, synthetic polymer, having a porosity between 50 to 95% and a median pore size between 100 and 300.

2. The matrix of claim 1, wherein the pore size is between approximately 150 and 250 microns and the porosity is between 75 and 95% and allows vascular ingrowth and the introduction of cells into the matrix without damage to the cells or patient.

3. The matrix of claim 1, wherein the biodegradable polymer is selected from the group consisting of polyanhydrides, polyorthoesters, polyglycolic acid, polylactic acid, copolymers and blends thereof.

4. The matrix of claim 1, further comprising a wetting agent.

5. The matrix of claim 1, wherein the polymer is an amorphous polymer.

6. The matrix of claim 1, wherein the polymer is a semicrystalline polymer.

7. The matrix of claim 1, further comprising means for introducing the cells into the matrix after implantation.

8. The matrix of claim 1, wherein the polymer is amorphous polylactic acid having 90% porosity and 200 micron median pore diameter.

9. The matrix of claim 1, further comprising cells selected from the group consisting of hepatocytes, pancreatic islet cells, fibroblasts, chondrocytes, osteoblasts, exocrine cells, cells of intestinal origin, bile duct cells, parathyroid cells, thyroid cells, cells of the adrenal-hypothalamic-pituitary axis, heart muscle cells, kidney epithelial cells, kidney tubular cells, kidney basement membrane cells, nerve cells, blood vessel cells, cells forming bone and cartilage, and smooth and skeletal muscle cells.

10. The matrix of claim 1, further comprising a material enhancing cell attachment to the polymer, wherein the material overlays the polymer.