Biocompatible polymer membranes and methods of preparation of three dimensional membrane structures

• US 5,514,378 A
• Filed: 02/01/1993
• Issued: 05/07/1996
• Est. Priority Date: 02/01/1993
• Status: Expired due to Term

• Current Assignee: Children's Medical Center Corporation
• Original Assignee: Children's Medical Center Corporation, Massachusetts Institute of Technology
• Inventors: Sarakinos, Georgios, Langer, Robert S., Vacanti, Joseph P., Mikos, Antonios G., Cima, Linda G.
• Primary Examiner(s): Kulkosky, Peter F.
• Application Number:
  US08/012,270
• Time in Patent Office: 1,191 Days
• Field of Search: 521/27, 424/426, 424/425
• US Class Current: 424/425
• 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 2/28 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 2/42 for wrists or ankles; for hands, e.g. fingers; for feet, e.g. toes
• 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 27/56 : Porous materials, e.g. foams or sponges
• CPC Class Codes: A61L 27/58 : Materials at least partially resorbable by the body
• CPC Class Codes: B01D 2323/12 : Specific ratios of components used
• CPC Class Codes: B01D 67/003 : by selective elimination of components, e.g. by leaching
• CPC Class Codes: B01D 67/0083 : Thermal after-treatment
• CPC Class Codes: B01D 71/40 : Polymers of unsaturated acids or derivatives thereof, e.g. salts, amides, imides, nitriles, anhydrides, esters
• CPC Class Codes: B01D 71/48 : Polyesters
• 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

Biocompatible porous polymer membranes are prepared by dispersing salt particles in a biocompatible polymer solution. The solvent in which the polymer is dissolved is evaporated to produce a polymer/salt composite membrane. The polymer can then be heated and cooled at a predetermined constant rate to provide the desired amount of crystallinity. Salt particles are leached out of the membrane by immersing the membrane in water or another solvent for the salt but not the polymer. The membrane is dried, resulting in a porous, biocompatible membrane to which dissociated cells can attach and proliferate. A three-dimensional structure can be manufactured using the polymer membranes by preparing a contour drawing of the shape of the structure, determining the dimensions of thin cross-sectional layers of the shape, forming porous polymer membranes corresponding to the dimensions of the layers, and laminating the membranes together to form a three-dimensional matrix having the desired shape.

Claims

1. A method of producing a biocompatible porous membrane comprising the steps of:

a) dispersing particles of a material selected from the group consisting of salts of an organic or inorganic compound, proteins, and polysaccharides having a diameter of less than 500 microns in a biocompatible polymer solution to form a particle and polymer composition having an initial polymer dry weight fraction of between 0.1 and 0.5 weight percent, wherein the polymer is dissolved in a non-aqueous solvent and is selected from the group consisting of poly(alpha esters), polyanhydrides, polyorthoesters, poly(vinyl alcohol), and ethylene vinyl acetate;

b) leaching the polymer solvent from the composition to form a membrane;

c) dissolving the particles from the membrane with a solvent for the particles without dissolving the polymer; and

d) removing the solvent for the particles by evaporation to form a porous membrane wherein the porosity is greater than 50%; and

e) modifying the crystallinity of the polymer by heating of the polymer.

2. The method of claim 1 wherein the crystallinity of the membrane is modified by melting the polymer in the composition and then cooling the composition before the dissolving step.

3. The method of claim 1 wherein the polymer is a biodegradable polymer selected from the group consisting of poly(hydroxy acids), polyanhydrides, and polyorthoesters.

4. The method of claim 1 wherein the particles have a diameter between 100 and 500 microns.

5. The method of claim 1 wherein the particles are added to the polymer solution in the range from 4.2 to 21.1 weight percent.

6. The method of claim 1 wherein the particle material is a biocompatible sodium salt.

7. The method of claim 1 wherein the membrane is cast into a mold having a desired shape.

8. The method of claim 1 wherein the membrane is between 500 and 2000 microns in thickness.

9. The method of claim 4 wherein the membrane has a porosity of greater than 90% in the form of interconnected interstitial spaces or pores.