Silk biomaterials and methods of use thereof

• US 8,071,722 B2
• Filed: 01/15/2010
• Issued: 12/06/2011
• Est. Priority Date: 06/24/2002
• Status: Expired due to Term

• Current Assignee: Massachusetts Institute of Technology, Trustees of Tufts College
• Original Assignee: Massachusetts Institute of Technology, Trustees of Tufts College
• Inventors: Kaplan, David L., Jin, Hyoung-Joon, Rutledge, Gregory, Fridrikh, Sergey
• Primary Examiner(s): DESAI, ANAND U
• Application Number:
  US12/688,014
• Publication Number:
  US 20100196447A1
• Time in Patent Office: 690 Days
• Field of Search: None
• US Class Current: 530/353
• 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 27/3604 characterised by the human or animal origin of the biological material, e.g. hair, fascia, fish scales, silk, shellac, pericardium, pleura, renal tissue, amniotic membrane, parenchymal tissue, fetal tissue, muscle tissue, fat tissue, enamel
• CPC Class Codes: A61L 27/44 having a macromolecular matrix
• CPC Class Codes: A61L 27/48 with macromolecular fillers
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: C08L 71/02 Polyalkylene oxides
• CPC Class Codes: D01D 5/0038 the fibre formed by solvent evaporation, i.e. dry electro-spinning
• CPC Class Codes: D01F 1/02 Addition of substances to the spinning solution or to the melt addition of substances to viscose D01F2/08
• CPC Class Codes: D01F 4/02 from fibroin
• CPC Class Codes: D01F 6/94 of other polycondensation products
• CPC Class Codes: D06M 13/17 Polyoxyalkyleneglycol ethers
• CPC Class Codes: D06M 15/03 Polysaccharides or derivatives thereof
• CPC Class Codes: D06M 15/11 Starch or derivatives thereof

Abstract

The present invention provides an all-aqueous process and composition for production of silk biomaterials, e.g., fibers, films, foams and mats. In the process, at least one biocompatible polymer, such as poly(ethylene oxide) (PEO) (a well-documented biocompatible material), was blended with the silk protein prior to processing e.g., electrospinning. We discovered that this step avoids problems associated with conformational transitions of fibroin during solubilization and reprocessing from aqueous solution which lead to embrittled materials. Moreover, the process avoids the use of organic solvents that can pose problems when the processed biomaterials are exposed to cells in vitro or in vivo.

Claims

1. A composition comprising a therapeutic agent and an aqueous solution of a silk fibroin obtained from silkworm silk or spider silk comprising a biocompatible polymer, wherein the aqueous solution of silk fibroin is free of solvents other than water.

2. The composition of claim 1, wherein the aqueous solution has a shear rate from 24.3 to 1216 per second at room temperature.

3. The composition of claim 1, wherein the aqueous solution has a conductivity of 19820 siemens at room temperature.

4. A composition comprising (i) fibroin obtained from silkworm silk or spider silk, (ii) a therapeutic agent and (iii) a biocompatible polymer selected from polyethylene oxide, fibronectin, polyaspartic acid, polylysine, pectin, dextrans, and combinations of two or more thereof, wherein the composition if free of solvents other than water.

5. The composition of claim 4, further comprising an aqueous solution.

6. The composition of claim 4, wherein the therapeutic agent is selected from the group consisting of antiinfectives, chemotherapeutic agents, anti-rejection agents, analgesics and analgesic combinations, anti-inflammatory agents, hormones and growth factors.

7. The composition of claim 4, wherein the therapeutic agent is selected from the group consisting of antibiotics, antiviral agents, steroids, bone morphogenic proteins, bone morphogenic-like proteins, epidermal growth factor, fibroblast growth factor, platelet derived growth factor, insulin-like growth factor, transforming growth factors and vascular endothelial growth factor.

8. The composition of claim 4, wherein the therapeutic agent is selected from proteins, polysaccharides, glycoproteins and lipoproteins.

9. The composition of claim 4, further comprising one or more additives.

10. The composition of claim 4, wherein the therapeutic agent is mixed with the biocompatible polymer.

11. The composition of claim 4, wherein the therapeutic agent is coated on to the composition.

12. The composition of claim 4, wherein the amount of therapeutic agent is about 0.001 percent to about 70 percent of the composition.

13. The composition of claim 4, wherein the therapeutic agent is released upon contact with a body fluid.

14. The composition of claim 4, wherein the biocompatible polymer is polyethylene oxide.

15. The composition of claim 4, wherein the composition is a fiber, a film, a foam or a mat.

16. A method for delivering a therapeutic agent comprising administering the composition of claim 4 to a patient in need thereof.

17. A method for repairing a wound comprising administering the composition of claim 4 to a patient in need thereof.

18. The composition of claim 4, wherein the therapeutic agent is selected from proteins, polysaccharides, glycoproteins and lipoproteins.

19. The compositions of claim 4, wherein the therapeutic agent is present as a liquid of a finely divided solid.