Porous polymer scaffolds for tissue engineering

• US 6,103,255 A
• Filed: 04/16/1999
• Issued: 08/15/2000
• Est. Priority Date: 04/16/1999
• Status: Active Grant

• Current Assignee: Rutgers University
• Original Assignee: Rutgers University
• Inventors: Kohn, Joachim B, Levene, Howard B., Lhommeau, Christelle M.
• Primary Examiner(s): Foelak, Morton
• Application Number:
  US09/293,118
• Time in Patent Office: 487 Days
• Field of Search: 521/61, 521/64, 521/916, 435/174, 435/180, 435/182, 424/426, 623/16
• US Class Current: 424/426
• CPC Class Codes: A61L 27/3839 characterised by the site of application in the body materials for artificial blood vessels A61L27/507; materials for use in artificial skin A61L27/60
• CPC Class Codes: A61L 27/56 Porous materials, e.g. foams or sponges
• CPC Class Codes: C08J 2201/044 Elimination of an inorganic solid phase
• CPC Class Codes: C08J 2201/0446 Elimination of NaCl only
• CPC Class Codes: C08J 2201/046 Elimination of a polymeric phase
• CPC Class Codes: C08J 2201/048 Elimination of a frozen liquid phase
• 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: C12N 2533/30 Synthetic polymers
• CPC Class Codes: C12N 5/0068 General culture methods using substrates for specific animal cell type C12N5/06

Abstract

Biodegradable and biocompatible porous scaffolds characterized by a substantially continuous polymer phase, having a highly interconnected bimodal distribution of open pore sizes with rounded large pores of about 50 to about 500 microns in diameter and rounded small pores less than 20 microns in diameter, wherein the small pores are aligned in an orderly linear fashion within the walls of the large pores. Methods of preparing polymeric tissue scaffolds are also disclosed.

Claims

1. A method for the preparation of biodegradable and biocompatible porous bimodal polymer scaffolds characterized by:

dissolving from about 0.5 to about 25 weight % of a biocompatible polymer in a miscible solvent mixture of a first solvent in which said polymer is soluble and a second solvent in which said polymer is insoluble, wherein the ratio of said first solvent to said second solvent is in a range within which said polymer dissolves to form a homogenous solution, and the first solvent has a melting point between about -40 and about 20°

C.;

placing said polymer solution into a form containing water-soluble non-toxic particles that are insoluble in organic solvents and have a diameter between about 50 and about 500 microns;

quenching said solution at a rate effective to result in crystallization of said first solvent before the onset of liquid-liquid demixing of said first and second solvent;

sublimating said polymer to remove said first and second solvents;

leaching said polymer with a solvent in which said particles are soluble and said polymer is insoluble to remove said particles from said polymer; and

drying said polymer.

2. The method of claim 1, characterized in that the ratio of said first solvent to said total solvent volume is between about 1% and about 40% v/v.

3. The method of claim 1, characterized in that said first solvent is 1,4-dioxane and said second solvent is water.

4. The method of claim 1, characterized in that said polymer is selected from the group consisting of biocompatible and biodegradable polycarbonates, polyarylates, block copolymers of polycarbonates with poly(alkylene oxides), block copolymers of polyarylates with poly(alkylene oxides), α

-hydroxycarboxylic acids, poly(capro-lactones), poly(hydroxybutyrates), polyanhydrides, poly(ortho esters), polyesters, and bisphenol-A based poly(phosphoesters).

5. The method of claim 1, characterized in that said particles are selected from the group consisting of alkali metal and alkaline earth metal halides, phosphates and sulfates, sugar crystals, water-soluble polymer microspheres and protein microspheres.

6. The method of claim 5, characterized in that said particles are sodium chloride crystals.

7. The method of claim 1, characterized in that said quenching step comprises immersing said solution in liquid nitrogen.

8. The method of claim 1, characterized in that said polymer is leached with water.

9. A polymeric tissue scaffold prepared by the method of claim 1.

10. The method of claim 1, characterized in that said polymer comprises an effective amount of a biologically active substance that either promotes or prevents a particular variety of cellular tissue ingrowth.

11. The method of claim 1, characterized in that said polymer comprises an effective amount of a pharmaceutically active compound.

12. A method of regulating cellular attachment, migration and proliferation on a polymeric substrate, characterized by contacting living cells, tissues or biological fluids containing living cells with the scaffold produced in the method of claim 10.