Porous biodegradable polymeric materials for cell transplantation

• US 6,689,608 B1
• Filed: 09/26/2000
• Issued: 02/10/2004
• Est. Priority Date: 02/01/1993
• Status: Expired due to Fees

• Current Assignee: Massachusetts Institute of Technology
• Original Assignee: Massachusetts Institute of Technology
• Inventors: Langer, Robert S., Vacanti, Joseph P., Mikos, Antonios G., Griffith, Linda G., Sarakinos, Georgios
• Primary Examiner(s): Naff, David M.
• Application Number:
  US09/669,760
• Time in Patent Office: 1,232 Days
• Field of Search: 435/174, 435/177, 435/180, 435/182, 435/395, 424/93.7, 424/423, 424/426
• US Class Current: 435/395
• CPC Class Codes: A61F 2/0077 Special surfaces of prostheses, e.g. for improving ingrowth A61F2/30767 takes precedence
• CPC Class Codes: A61F 2/18 Internal ear or nose parts, e.g. ear-drums implants for middle ear ventilation or drainage A61F11/202
• CPC Class Codes: A61F 2/186 Nose parts
• CPC Class Codes: A61F 2/28 Bones joints A61F2/30
• CPC Class Codes: A61F 2/30756 Cartilage endoprostheses A61F2/3603 takes precedence
• CPC Class Codes: A61F 2/3094 Designing or manufacturing processes
• CPC Class Codes: A61F 2/30942 for designing or making customized prostheses, e.g. using templates, CT or NMR scans, finite-element analysis or CAD-CAM techniques
• CPC Class Codes: A61F 2/4241 for hands, e.g. fingers
• CPC Class Codes: A61F 2002/30011 differing in porosity
• CPC Class Codes: A61F 2002/30062 (bio)absorbable, biodegradable, bioerodable, (bio)resorbable, resorptive
• CPC Class Codes: A61F 2002/30156 triangular
• CPC Class Codes: A61F 2002/30299 umbrella-shaped or mushroom-shaped
• CPC Class Codes: A61F 2002/30304 nose-shaped
• CPC Class Codes: A61F 2002/30929 having at least two superposed coatings
• CPC Class Codes: A61F 2002/30971 Laminates, i.e. layered products
• CPC Class Codes: A61F 2002/4251 for metacarpo-phalangeal joints, i.e. MCP or MP joints, e.g. knuckle joints
• CPC Class Codes: A61F 2210/0004 bioabsorbable
• CPC Class Codes: A61F 2230/0023 triangular
• CPC Class Codes: A61F 2230/0063 Three-dimensional shapes
• CPC Class Codes: A61F 2230/0093 Umbrella-shaped, e.g. mushroom-shaped
• CPC Class Codes: A61F 2240/001 : Designing or manufacturing processes
• CPC Class Codes: A61F 2240/002 : Designing or making customized prostheses
• CPC Class Codes: A61F 2250/0023 : differing in porosity
• 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: A61P 17/02 : for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: B01D 2325/0283 : Pore size
• CPC Class Codes: B01D 67/003 : by selective elimination of components, e.g. by leaching
• 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: C08J 9/28 : by elimination of a liquid phase from a macromolecular composition or article, e.g. drying of coagulum
• CPC Class Codes: C08L 67/04 : Polyesters derived from hydroxycarboxylic acids, e.g. lactones C08L67/06 takes precedence

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 formed of a biodegradable, biocompatible, synthetic, amorphous polymer or semi-crystalline polymer with a degree of crystallinity in the range of from 0 to 24.5% having a porosity of between 45 to 93% and a pore size range of greater than zero to 500 microns that is suitable for attachment and proliferation of dissociated cells.

2. 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.

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

4. The matrix of claim 1, wherein the polymer is a semi-crystalline polymer.

5. The matrix of claim 1, further comprising a catheter for introducing cells into the interior pores of the matrix after implantation.

6. The matrix of claim 1, wherein the median pore diameter is up to 150 microns.

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