IP Library Granted Patent US 8,728,498
Granted Patent B2
US 8,728,498 · App. 13/382,967 · Granted May 20, 2014

Electrospun silk material systems for wound healing

Inventors: Xiaohui Zhang (Westmont, IL); David L. Kaplan (Concord, MA); Scott E. Wharram (Pepperell, MA); Stephen McCarthy (Tyngsboro, MA)
Assignee: Trustees of Tufts College
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Quick Facts
Patent No.
US 8,728,498
App. No.
13/382,967
Granted
May 20, 2014
Kind
B2
Abstract

The present invention relates to the processes of preparing silkfibroin/polyethylene oxide blended materials, and the resulting materials thereof, which are suitable for biomedical applications such as wound healing. In particular, the electrospun silk fibroin/PEO mats with a silk:PEO blend ratio of 2:1 to 4:1, treated with controlled evaporation, constraint-drying techniques, and/or alcohol treatment, and/or PEO extraction, demonstrate suitable physical and biofunctional properties, such as fiber structure, topography, absorption, water vapor transmission rates, oxygen permeation, and biodegradability, relevant to biomaterial systems with utility for wound dressings.

Claims (26)

1. A process for producing a silk mat, comprising: electrospinning a blended polyethylene oxide (PEO) and aqueous silk fibroin solution, thereby forming a silk protein/PEO blended mat; and constraint-drying the electrospun silk mat, wherein the silk mat has a silk fibroin content ranging from about 50 wt % to about 100 wt % and wherein the silk mat has a thickness of about 20-30 microns.

2. The process of claim 1 , further comprising treating the electrospun silk mat with alcohol.

3. The process of claim 1 , further comprising extracting the PEO from the silk mat.

4. The process of claims 1 , further comprising embedding at least one active agent in the silk mat.

5. The process of claim 4 , wherein the active agent is a therapeutic agent or a biological material, selected from the group consisting of cells, proteins, peptides, nucleic acids, nucleic acid analogs, nucleotides or oligonucleotides, peptide nucleic acids, aptamers, antibodies or fragments or portions thereof, antigens or epitopes, hormones, hormone antagonists, growth factors or recombinant growth factors and fragments and variants thereof, cell attachment mediators, cytokines, enzymes, antibiotics or antimicrobial compounds, viruses, toxins, prodrugs, chemotherapeutic agents, small molecules, drugs, and combinations thereof.

6. The process of claim 5 , wherein the active agent is a cell selected from the group consisting of progenitor cells or stem cells, smooth muscle cells, skeletal muscle cells, cardiac muscle cells, epithelial cells, endothelial cells, urothelial cells, fibroblasts, myoblasts, oscular cells, chondrocytes, chondroblasts, osteoblasts, osteoclasts, keratinocytes, kidney tubular cells, kidney basement membrane cells, integumentary cells, bone marrow cells, hepatocytes, bile duct cells, pancreatic islet cells, thyroid, parathyroid, adrenal, hypothalamic, pituitary, ovarian, testicular, salivary gland cells, adipocytes, precursor cells, and combinations thereof.

7. The process of claim 6 , the active agent further comprises a cell growth media.

8. The process of claim 6 , wherein the active agent is an antibiotic.

9. An electrospun silk mat comprising a silk fibroin protein content ranging from about 50 wt % to about 100 wt %, wherein the silk mat has a thickness of about 20-30 microns.

10. The electrospun silk mat of claim 9 , wherein the content of silk fibroin protein in the electrospun silk mat ranges from about 75 wt % to about 90 wt %.

11. The electrospun silk mat of claim 9 , further comprising upto 50 wt % of a polyethylene oxide (PEO) in the electrospun silk mat.

12. The electrospun silk mat of claim 11 , wherein the electrospun silk mat comprises PEO in an amount from about 10 wt % to about 25 wt %.

13. The electrospun silk mat of claim 9 , further comprising at least one active agent.

14. The electrospun silk mat of claim 13 , wherein the active agent is a therapeutic agent or a biological material, selected from the group consisting of cells, proteins, peptides, nucleic acids, nucleic acid analogs, nucleotides or oligonucleotides, peptide nucleic acids, aptamers, antibodies or fragments or portions thereof, antigens or epitopes, hormones, hormone antagonists, growth factors or recombinant growth factors and fragments and variants thereof, cell attachment mediators, cytokines, enzymes, antibiotics or antimicrobial compounds, viruses, toxins, prodrugs, chemotherapeutic agents, small molecules, drugs, and combinations thereof.

15. The electrospun silk mat of claim 9 , wherein the silk mats have interconnected pores with a pore diameter averaging from about 0.1 to about 0.3 microns.

16. The electrospun silk mat claim 9 , wherein the silk mat has a water absorption content of more than about 460%.

17. The electrospun silk mat of claim 14 , wherein the active agent is a cell selected from the group consisting of progenitor cells or stem cells, smooth muscle cells, skeletal muscle cells, cardiac muscle cells, epithelial cells, endothelial cells, urothelial cells, fibroblasts, myoblasts, oscular cells, chondrocytes, chondroblasts, osteoblasts, osteoclasts, keratinocytes, kidney tubular cells, kidney basement membrane cells, integumentary cells, bone marrow cells, hepatocytes, bile duct cells, pancreatic islet cells, thyroid, parathyroid, adrenal, hypothalamic, pituitary, ovarian, testicular, salivary gland cells, adipocytes, precursor cells, and combinations thereof.

18. The electrospun silk mat of claim 14 , wherein the silk mat further comprises a cell growth media.

19. The electrospun silk mat of claim 14 , wherein the active agent is an antibiotic.

20. A method of promoting wound healing comprising contacting a wound with at least one electrospun silk mat comprising a silk fibroin protein and, optionally, at least one active agent;

wherein the silk fibroin protein ranges from about 50 wt % to about 90 wt %,

wherein the silk mat has a thickness of about 20 microns to about 30 microns;

wherein the silk mat has a water absorption content of more than about 460%, or equilibrium water content more than about 82%; and

wherein the resulting silk mat has an oxygen transmission rate of more than about 15460 cm 3 /m 2 /day.

21. The method of claim 20 , wherein the silk fibroin protein ranges from about 75 wt % to about 90 wt %.

22. A method of promoting wound healing comprising contacting a wound with at least one electrospun silk mat of claim 9 .

Assignments (4)
CONFIRMATORY LICENSE Recorded Oct 19, 2012
From: TUFTS UNIVERSITY BOSTON
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 029156/0588 →
CORRECTIVE ASSIGNMENT TO CORRECT THE ASSIGNEE NAME PREVIOUSLY RECORDED ON REEL 027507 FRAME 0319. ASSIGNOR(S) HEREBY CONFIRMS THE ASSIGNEE NAME: THE UNIVERSITY OF MASSACHUSETTS FOUNDATION, INC. SHOULD BE CORRECTED TO UNIVERSITY OF MASSACHUSETTS. Recorded Apr 3, 2012
From: WHARRAM, SCOTT E.; MCCARTHY, STEPHEN
To: UNIVERSITY OF MASSACHUSETTS
Reel/Frame 027976/0450 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 10, 2012
From: WHARRAM, SCOTT E.; MCCARTHY, STEPHEN
To: THE UNIVERSITY OF MASSACHUSETTS FOUNDATION, INC.
Reel/Frame 027507/0319 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 10, 2012
From: ZHANG, XIAOHUI; KAPLAN, DAVID L.
To: TRUSTEES OF TUFTS COLLEGE
Reel/Frame 027507/0324 →
Continuity (2)
Provisional Application 61225335 · Jul 14, 2009
Related Publication 20120171256A1 · Jul 5, 2012