Tissue-engineering scaffolds containing self-assembled-peptide hydrogels

• US 20080145934A1
• Filed: 09/28/2004
• Published: 06/19/2008
• Est. Priority Date: 09/28/2004
• Status: Active Grant

• Current Assignee: Advanced Technologies and Regenerative Medicine, LLC
• Original Assignee: Advanced Technologies and Regenerative Medicine, LLC
• Inventors: Harmon, Alexander M., Gosiewska, Anna, Brown, Laura J., Harris, Ian Ross
• Granted Patent: US 8,039,258 B2
• Time in Patent Office: Days
• 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 tissue-engineering scaffold, comprising

a microporous scaffold comprising a biocompatible material suitable for use in tissue-engineering scaffolds;

and

a nanofiberous, nanoporous hydrogel formed from self-assembling peptides.

2. The tissue-engineering scaffold of claim 1 wherein said microporous scaffold is in a form selected from the group consisting of a solid-cast structure, open-pore foam, felts, meshes, nonwoven, woven and knitted constructs.

3. The tissue-engineering scaffold of claim 1 wherein said biocompatible material is selected from the group consisting of biocompatible metals, bioinert ceramics and biocompatible polymers.

4. The tissue-engineering scaffold of claim 3 wherein said biocompatible polymer comprises a biodegradable polymer.

5. The tissue-engineering scaffold of claim 4 wherein said biodegradable polymer is selected from the group consisting of poly(lactic acid), poly(L-lactic acid), poly(D-lactic acid), poly(glycolic acid), polycaprolactone, poly(epsilon-caprolactone), poly(lactide-co-glycolide), poly(epsilon-caprolactone-co-glycolide), poly(epsilon-caprolactone-co-L-lactide), polydioxanone, polygluconate, poly(lactic acid-co-ethylene oxide), modified cellulose, collagen, polyhydroxybutyrate, poly(hydroxpriopionic acid), polyphosphoester, poly(alpha-hydroxy acid), polycarbonates, polyamides, polyanhydrides, polyamino acids, polyorthoesters and biodegradable polyurethanes.

6. The tissue-engineering scaffold of claim 5 wherein said biodegradable polymer is selected from the group consisting of poly(lactic acid), poly(glycolic acid), poly(epsilon-caprolactone), polydioxanone, poly(lactide-co-glycolide), poly(epsilon-caprolactone-co-glycolide) and poly(epsilon-caprolactone-co-L-lactide).

7. The tissue-engineering scaffold of claim 3 wherein said biocompatible polymer comprises a nondegradable polymer.

8. The tissue-engineering scaffold of claim 7 wherein said biocompatible polymer is a nonbiodegradable polymer 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.

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

10. The 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.

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

12. The tissue-engineering scaffold of claim 1 wherein said self-assembling peptide comprises fibers having a diameter of from about 5 to about 50 nanometers.

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

14. The tissue engineering scaffold of claim 1 wherein said self-assembling peptides comprise more than about 12 alternating hydrophobic and hydrophilic amino acids.

15. The tissue engineering scaffold of claim 1 wherein said nanofiberous, nanoporous self-assembling peptide is selected from the group consisting of NH₂-RADARADARADARADA-COOH, NH₂-KLDLKLDLKLDL-COOH peptide fragment AAAAGGGS and peptide fragment CCCCGGGS.

16. The tissue-engineering scaffold of claim 1 wherein said hydrogel comprises of about 0.5 to about 20 milligrams per milliliter of said self-assembling peptide.

17. The tissue-engineering scaffold of claim 1 wherein said microporous scaffold comprises from about 0.1 to about 10 micrograms per cubic millimeter of said self-assembling-peptide hydrogel.

18. The tissue-engineering scaffold of claim 1 wherein at least a portion of said hydrogel is disposed within pores of said microporous scaffold.