NOVEL NANOFIBER-BASED GRAFTS AND METHODS OF MAKING AND USING THE SAME

• US 20200129665A1
• Filed: 04/04/2018
• Published: 04/30/2020
• Est. Priority Date: 04/04/2017
• Status: Abandoned Application

• Current Assignee: Wake Forest University Health Sciences
• Original Assignee: Wake Forest University Health Sciences
• Inventors: Wagner, William D., Warner, Harleigh J.
• Application Number:
  US16/493,458
• Publication Number:
  US 20200129665A1
• Time in Patent Office: Days
• CPC Class Codes: A61L 2400/12 Nanosized materials, e.g. nanofibres, nanoparticles, nanowires, nanotubes; Nanostructured surfaces
• CPC Class Codes: A61L 2430/20 for reconstruction of the heart, e.g. heart valves
• CPC Class Codes: A61L 27/26 Mixtures of macromolecular compounds
• CPC Class Codes: A61L 27/3804 characterised by specific cells or progenitors thereof, e.g. fibroblasts, connective tissue cells, kidney cells
• CPC Class Codes: A61L 27/507 for artificial blood vessels apparatus for applying cells on a blood vessel prosthesis A61F2/062
• CPC Class Codes: C08L 89/00 Compositions of proteins; Compositions of derivatives thereof foodstuff preparations A23J3/00

Abstract

Nanofiber-based biomaterials containing fibroin for wound repair and tissue replacement are provided with methods of making and using the same.

Claims

1. :

An electrospun fiber material comprising a collagen, a fibroin, and a hemocompatible synthetic elastomer,

wherein said electrospun nanofiber material further comprises extracellular matrix and/or a heparan sulfate glycoprotein.

2. :

The electrospun fiber material of claim 1 comprising a heparan sulfate glycoprotein.

3. :

The electrospun fiber material of claim 1 comprising extracellular matrix.

4. :

The electrospun fiber material of claim 2, wherein said heparin sulfate glycoprotein is covalently linked to said electrospun fiber material.

5. :

The electrospun fiber material of claim 4, wherein said heparin sulfate glycoprotein is a syndecan.

6. :

The electrospun fiber material of claim 5, wherein said syndecan is syndecan-4.

7. :

The electrospun fiber material of claim 1, further comprising stromal cell-derived factor 1 (SDF-1α

).

8. :

The electrospun fiber material of claim 1, wherein the collagen is type I collagen.

9. :

The electrospun fiber material of claim 1, wherein the fibroin is silk fibroin.

10. :

The electrospun fiber material of claim 1, wherein the hemocompatible synthetic elastomer is a poly glycerol derivative ester comprising a polycarboxylic acid.

11. :

The electrospun fiber material of claim 1, wherein the hemocompatible synthetic elastomer is poly (glycerol sebacate).

12. :

The electrospun fiber material of claim 1, comprising type I collagen, silk fibroin, and poly (glycerol sebacate).

13. :

The electrospun fiber material of claim 1, wherein the weight ratio for the collagen is about 25% to about 65% per total composition weight of said collagen, fibroin, and hemocompatible synthetic elastomer.

14. :

The electrospun fiber material according to claim 13, wherein the weight ratio for the collagen is about 45% per total composition weight of said collagen, fibroin, and hemocompatible synthetic elastomer.

15. :

The electrospun fiber material of claim 1, wherein the weight ratio for the fibroin is about 25% to about 65% per total composition weight of said collagen, fibroin, and hemocompatible synthetic elastomer.

16. :

The electrospun fiber material according to claim 15, wherein the weight ratio for the fibroin is about 45% per total composition weight of said collagen, fibroin, and hemocompatible synthetic elastomer.

17. :

The electrospun fiber material of claim 1, wherein the weight ratio for the hemocompatible synthetic elastomer is about 10% to about 20% per total composition weight of said collagen, fibroin, and hemocompatible synthetic elastomer.

18. :

The electrospun fiber material according to claim 17, wherein the weight ratio for the hemocompatible synthetic elastomer is about 10% per total composition weight of said collagen, fibroin, and hemocompatible synthetic elastomer.

19. :

The electrospun fiber material of claim 1, wherein the weight ratio for the hemocompatible synthetic elastomer is about 10%, the weight ratio for the collagen is about 45%, and the weight ratio for the fibroin is about 45% per total composition weight of said collagen, fibroin, and hemocompatible synthetic elastomer.

20. :

The electrospun fiber material of claim 1, further comprising an electronegative carbohydrate, a glycosaminoglycan, a growth factor, a cell signaling molecule, or a combination thereof.

21. :

The electrospun fiber material of claim 1, wherein the fibers have a diameter of about 600 to about 5000 nm.

22. :

A porous electrospun graft material configured to replace biological tissue comprising the electrospun fiber material of claim 1.

23. :

The porous electrospun graft material according to claim 22, wherein the graft material is shaped as a heart valve, an aortic heart valve, a stent, a sheet, or a conduit.

24. :

The porous electrospun graft material according to claim 22, wherein the graft material is shaped as an arterial or venous conduit, particularly with a diameter less than 6 mm.

25. :

The porous electrospun graft material according to claim 22, wherein the graft has an elastic modulus from about 2 to about 5 Mpa.

26. :

The porous electrospun graft material according to claim 22, wherein the graft has a stress value of about 0.6 to 2.0 Mpa.

27. :

The porous electrospun graft material according to claim 22, wherein the graft has a strain value of about 0.2 to 0.7 mm/mm.

28. :

A method of preparing the electrospun fiber material of claim 1, the method comprising the steps of;

a. electrospinning a solution comprising collagen, fibroin and a hemocompatible synthetic elastomer into an interconnected fiber matrix;

b. culturing the interconnected fiber matrix of step a) with extracellular matrix producing cells; and

c. collecting the interconnected fiber matrix, thereby preparing said electrospun fiber material.

29. :

The method of claim 28, wherein step (a) comprises electrospinning the solution onto a mold.

30. :

The method of claim 28, further comprising the step of curing the interconnected fiber matrix of step a) by heating the interconnected fiber matrix and/or crosslinking.

31. :

The method of claim 28, wherein the extracellular matrix producing cells are fibroblasts.

32. :

The method of claim 28, wherein the interconnected fiber matrix is cultured with said extracellular matrix producing cells for about 1 to about 30 days.

33. :

The method of claim 28, further comprising lysing the cultured cells by delivering a lysing agent to the cells cultured with the interconnected fiber matrix.

34. :

The method of claim 33, wherein said lysing agent is a non-ionic detergent.

35. :

A method of preparing the electrospun fiber material of claim 1, the method comprising the steps of;

a. electrospinning a solution comprising collagen, fibroin and a hemocompatible synthetic elastomer into an interconnected fiber matrix;

b. crosslinking said heparan sulfate glycoprotein to the interconnected fiber matrix of step a), thereby preparing said electrospun fiber material.

36. :

The method of claim 35, wherein step b) is performed with a carbodiimide crosslinker.

37. :

The method of claim 35, further comprising the step of curing the interconnected fiber matrix of step a) by heating the interconnected fiber matrix and/or crosslinking prior to step b).