IP Library Granted Patent US 9,993,527
Granted Patent B2
US 9,993,527 · App. 13/680,570 · Granted Jun 12, 2018

Silk fibroin materials and use thereof

Inventors: David L. Kaplan (Concord, MA); Rina Sears (Pine Meadow, CT); Gordana Vunjak-Novakovic (New York, NY); Lorenz Meinel (Niestetal, DE)
Assignees: TRUSTEES OF TUFTS COLLEGE; MASSACHUSETTS INSTITUTE OF TECHNOLOGY
A61K38/1825A61K38/1841A61K47/42A61L27/227A61L27/26A61L27/3604A61L27/3847A61L27/3852A61L27/3895A61L27/56D01D5/00D01F4/02Y10T428/29
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Quick Facts
Patent No.
US 9,993,527
App. No.
13/680,570
Granted
Jun 12, 2018
Kind
B2
Abstract

The present invention provides processes for producing porous silk fibroin scaffold material. The porous silk fibroin scaffold can be used for tissue engineering. The porosity of the silk fibroin scaffolds described herein can be adjusted as to mimic the gradient of densities found in natural tissue. Accordingly, methods for engineering of 3-dimensional tissue, e.g. bone and cartilage, using the silk fibroin scaffold material are also provided.

Claims (19)

1. A three-dimensional body comprising silk fibroin having interconnected pores, wherein the pores have a diameter of 155 to 1000 microns, and a peptide comprising an integrin binding sequence.

2. The three-dimensional body of claim 1 , wherein the integrin binding sequence comprises the amino acid sequence RGD.

3. The three-dimensional body of claim 1 , wherein the peptide comprising the integrin binding sequence is cross-linked with the silk fibroin.

4. The three-dimensional body of claim 1 , wherein the silk fibroin is in a beta-sheet conformation.

5. The three-dimensional body of claim 1 , wherein the three-dimensional body comprises from 5% (w/v) to 35% (w/v) of the silk fibroin.

6. The three-dimensional body of claim 1 , wherein the silk fibroin is substantially free of sericin.

7. The three-dimensional body of claim 1 , wherein the three-dimensional body is an article for tissue engineering or tissue guided regeneration application.

8. The three-dimensional body of claim 1 , wherein the three-dimensional body has a porosity above 80%.

9. The three-dimensional body of claim 1 , wherein the three-dimensional body further comprises an additive.

10. The three-dimensional body of claim 9 , wherein the additive is selected from peptides, antibodies, DNA, RNA, modified RNA/protein composites, glycogens or other sugars and alcohols.

11. The three-dimensional body of claim 9 , wherein the additive is a biologically active or pharmaceutically active compound.

12. The three-dimensional body of claim 9 , wherein the additive is an agent that enhances proliferation or differentiation of a cell.

13. The three-dimensional body of claim 9 , wherein the additive is a bone morphogenic protein, a basic fibroblast growth factor, an epidermal growth factor, a platelet-derived growth factor, an insulin-like growth factor or a transforming growth factor.

14. The three-dimensional body of claim 9 , wherein the additive is selected from the group consisting of collagen, elastin, fibronectin, vitronectin, laminin and proteoglycans.

15. The three-dimensional body of claim 1 , wherein the silk fibroin is selected from the group consisting of silks from silkworms, silks from spiders, silks from genetically engineered cells, silks from transgenic plants and animals, silks from cultured cells, native silk, silk from cloned full or partial sequences of native silk genes, and silk from synthetic genes encoding silk.

16. The three-dimensional body of claim 1 , wherein the three-dimensional body comprises a cell.

17. A silk fibroin material comprising silk fibroin produced by boiling cocoons for about 30 minutes to about 1 hour for extracting sericin, wherein the silk fibroin is coupled to a peptide comprising an integrin binding sequence.

18. A three-dimensional silk fibroin body comprising interconnected pores having diameter size of 50-1000 micrometers, wherein the three-dimensional silk fibroin body is coupled to a peptide comprising an integrin binding sequence and further comprises a biodegradable polymer selected from the group consisting of collagens, polylactic acid or its copolymers, polyglycolic acid or its copolymers, polyanhydrides, elastin, glycosaminoglycans, polysaccharides, and any combinations thereof.

19. The three-dimensional body of claim 1 , wherein the peptide comprising the integrin binding sequence is coupled to the silk fibroin.

Assignments (3)
CONFIRMATORY LICENSE Recorded Oct 20, 2016
From: TUFTS UNIVERSITY BOSTON
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 040427/0043 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 5, 2014
From: KAPLAN, DAVID L.; NAZAROV, RINA
To: TRUSTEES OF TUFTS COLLEGE
Reel/Frame 032351/0559 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 5, 2014
From: VUNJAK-NOVAKOVIC, GORDANA; MEINEL, LORENZ
To: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
Reel/Frame 032351/0575 →
Continuity (4)
Continuation 12836692 · Jul 15, 2010
Continuation 10541182
Provisional Application 60438393 · Jan 7, 2003
Related Publication 20140094410A1 · Apr 3, 2014