Tissue-engineering scaffolds containing self-assembled-peptide hydrogels

• US 8,039,258 B2
• Filed: 09/28/2004
• Issued: 10/18/2011
• Est. Priority Date: 09/28/2004
• Status: Active Grant

• Current Assignee: Advanced Technologies and Regenerative Medicine, LLC
• Original Assignee: Ethicon Incorporated (Johnson & Johnson)
• Inventors: Brown, Laura J., Harris, Ian Ross, Harmon, Alexander M., Gosiewska, Anna
• Primary Examiner(s): Long; Scott
• Application Number:
  US10/951,357
• Publication Number:
  US 20080145934A1
• Time in Patent Office: 2,576 Days
• Field of Search: None
• US Class Current: 435/404
• CPC Class Codes: A61L 27/227 Other specific proteins or polypeptides not covered by A61L27/222, A61L27/225 or A61L27/24
• CPC Class Codes: A61L 27/52 Hydrogels or hydrocolloids
• CPC Class Codes: A61L 27/56 Porous materials, e.g. foams or sponges
• CPC Class Codes: C12N 2533/40 Polyhydroxyacids, e.g. polymers of glycolic or lactic acid (PGA, PLA, PLGA); Bioresorbable polymers
• CPC Class Codes: C12N 2533/50 Proteins
• CPC Class Codes: C12N 5/06 Animal cells or tissues; Human cells or tissues preservation of living cells or tissues A01N1/02

Abstract

The present invention is directed to tissue-engineering scaffolds containing both a microporous scaffold made from a biocompatible material suitable for use in tissue-engineering scaffolds and a nanofiberous, nanoporous hydrogel formed from a self-assembling peptide, where at least a portion of the hydrogel is disposed within the pores of the microporous scaffold, thus providing tissue-engineering scaffolds having average pore diameters in the nanometer range and that provide both mechanical properties suitable for implantation into a body of a mammal and excellent tissue response once implanted in the body.

Claims

1. A cell-free tissue-engineering scaffold, comprising:

a) a microporous scaffold comprising a poly(lactide-co-glycolide) co-polymer; and

b) a nanofibrous, nanoporous hydrogel coating on a surface of said scaffold, wherein said coating is formed from self-assembling peptides selected from the group consisting of NH₂-RADARADARADARADA-COOH (SEQ ID NO;

1) and NH₂-KLDLKLDLKLDL-COOH (SEQ ID NO;

2), and wherein at least a portion of said hydrogel is disposed within pores of said microporous scaffold.

2. The cell-free tissue-engineering scaffold of claim 1 wherein said microporous scaffold has a porosity from 85 to 99 percent.

3. The cell-free tissue-engineering scaffold of claim 1 wherein said microporous scaffold comprises pores having an average pore diameter of from 1 to about 2,000 microns.

4. The cell-free tissue-engineering scaffold of claim 1 wherein the thickness of said microporous scaffold is from about 300 to about 3,000 microns.

5. The cell-free tissue-engineering scaffold of claim 1 wherein said hydrogel comprises fibers having a diameter of from about 5 to about 50 nanometers.

6. The cell-free tissue-engineering scaffold of claim 1 wherein said hydrogel comprises pores having an average diameter of from about 50 to about 400 nanometers.

7. The cell-free tissue-engineering scaffold of claim 1 wherein said self-assembling peptides are in a solution which comprises of about 0.5 to about 20 milligrams per milliliter of said self-assembling peptide.

8. The cell-free tissue-engineering scaffold of claim 1 wherein the self-assembling peptides and microporous scaffold have a weight to volume relation of about 0.1 to about 10 micrograms of peptide per cubic millimeter of microporous scaffold.

9. The cell-free tissue-engineering scaffold of claim 1 wherein the self-assembling peptides and microporous scaffold have a weight to volume relation of about 0.1 to about 5 micrograms of peptide per cubic millimeter of microporous scaffold.

10. The cell-free tissue-engineering scaffold of claim 1 wherein the self-assembling peptides and microporous scaffold have a weight to volume relation of about 0.1 to about 1 micrograms of peptide per cubic millimeter of microporous scaffold.

11. The cell-free tissue-engineering scaffold of claim 1, and wherein the self-assembling peptide is NH₂-RADARADARADARADA-COOH (SEQ ID NO:

1).

12. The cell-free tissue-engineering scaffold of claim 1, wherein the self-assembling peptide is NH₂-KLDLKLDLKLDL-COOH (SEQ ID NO:

2).

13. A cell-free tissue-engineering scaffold, comprising:

a) a unitary microporous scaffold formed of a nonbiodegradable polymer suitable for use in tissue-engineering scaffolds; and

b) a nanofibrous, nanoporous hydrogel coating on a surface of said scaffold wherein said coating is formed from self-assembling peptides selected from the group consisting of NH₂-RADARADARADARADA-COOH (SEQ ID NO;

1) and NH₂-KLDLKLDLKLDL-COOH (SEQ ID NO;

2), and wherein at least a portion of said hydrogel is disposed within pores of said microporous scaffold.

14. The tissue-engineering scaffold of claim 13, wherein said nonbiodegradable polymer is selected from the group consisting of aliphatic polyesters, polyacrylates, polymethacrylates, acyl-substituted cellulose acetates, nonbiodegradable polyurethanes, polystyrenes, polyvinyl chloride, polyvinyl flouride, polyvinyl imidazole, chlorosulphonated polyolifins, polyethylene oxide, polyvinyl alcohol, polytetrafluoroethylene, nylon, silicon, poly(styrene-block-butadiene), polynorbomene, ceramics, and metallic alloys.