Method of forming a tissue structure by introducing cells into an implanted matrix

• US 8,110,213 B2
• Filed: 07/15/2008
• Issued: 02/07/2012
• Est. Priority Date: 02/01/1993
• Status: Expired due to Fees

• Current Assignee: Children's Medical Center Corporation
• Original Assignee: Children's Medical Center Corporation, Massachusetts Institute of Technology
• Inventors: Mikos, Antonios G., Langer, Robert S., Vacanti, Joseph P., Griffith, Linda G., Sarakinos, Georgios
• Primary Examiner(s): NAFF, DAVID M
• Application Number:
  US12/218,448
• Publication Number:
  US 20090060969A1
• Time in Patent Office: 1,302 Days
• Field of Search: None
• US Class Current: 424/426
• 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 2325/02 : Details relating to pores or porosity of the membranes
• 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 method of forming a tissue structure comprising the steps of:

(a) implanting into a patient a polymeric matrix lacking cells, wherein said 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 microns; and

(b) introducing dissociated cells into the implanted matrix of step (a),

wherein the implanted matrix in step (b) is vascularized, thereby forming a tissue structure in said patient.

2. The method of claim 1, wherein the matrix has a pore size between approximately 150 and 250 microns and porosity between 75% and 95% and allows for the introduction of dissociated cells into the implanted matrix without damage to the cells or the patient.

3. The method 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 method of claim 1, wherein said matrix further comprises a wetting agent.

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

6. The method of claim 1, wherein the polymer is semicystalline polymer.

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

8. The method of claim 1, wherein said dissociated cells are 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 cells, kidney tubular cells, kidney basement membrane cells, nerve cells, blood vessel cells, cells forming bone and cartilage, and smooth and skeletal muscle cells.

9. The method of claim 1, wherein the matrix further comprises a material enhancing cell attachment to the polymer, wherein the material overlays the polymer.