Electrospun cell matrices

• US 9,163,331 B2
• Filed: 11/18/2009
• Issued: 10/20/2015
• Est. Priority Date: 03/11/2005
• Status: Active Grant

• Current Assignee: Wake Forest University Health Sciences
• Original Assignee: Wake Forest University Health Sciences
• Inventors: Atala, Anthony, Yoo, James, Lim, Grace, Czerw, Richard, Soker, Shay, Stitzel, Joel
• Primary Examiner(s): Sharma, Yashita
• Application Number:
  US12/621,052
• Publication Number:
  US 20100129450A1
• Time in Patent Office: 2,162 Days
• Field of Search: 623/13.11, 623/13.12, 623/13.17, 623/13.18, 623/13.2, 623/14.13, 623/23.72, 623 11- 125, 623 13- 154, 623 2364- 2367, 623 237- 2371, 536/123, 514/12.1, 264/466, 435/325, 435/402, 435/446, 424/484, 424486-488, 424/496
• US Class Current: 1/1
• CPC Class Codes: C12N 2533/40 Polyhydroxyacids, e.g. polymers of glycolic or lactic acid (PGA, PLA, PLGA); Bioresorbable polymers
• CPC Class Codes: C12N 2533/54 Collagen; Gelatin
• CPC Class Codes: C12N 5/0691 Vascular smooth muscle cells; 3D culture thereof, e.g. models of blood vessels
• CPC Class Codes: D01D 5/0007 Electro-spinning non-woven fabrics produced by electro-spinning D04H1/728
• CPC Class Codes: D01F 4/00 Monocomponent artificial filaments or the like of proteins; Manufacture thereof
• CPC Class Codes: D01F 6/92 of polyesters

Abstract

The invention is directed to compositions and methods for preparing electrospun matrices comprising at least one natural biological material component and at least one synthetic polymer material. The natural component makes the matrices highly biocompatible while the molecular weight polymer component can impart additional strength mechanical strength to the scaffold and/or improve ease of manufacture by increasing viscosity and spinning characteristics of the solution during electrospining.

Claims

1. An electrospun tubular composite matrix for use as a vascular construct comprising electrospun polycaprolactone and at least one electrospun natural component, wherein the matrix has a three-dimensional ultrastructure of interconnected polycaprolactone and natural component fibers with an average diameter from 50 nanometers to 800 nanometers and pores to permit cell attachment and differentiation into a tissue layer and sufficient mechanical burst strength to withstand pressure up to 1,425 mmHg.

2. The matrix of claim 1 wherein the natural component further comprises collagen.

3. The matrix of claim 2, wherein the collagen comprises from 25 percent to 75 percent by weight of the matrix.

4. The matrix of claim 1, wherein the natural component comprises elastin.

5. The matrix of claim 1, wherein the natural component comprises both collagen and elastin.

6. The matrix of claim 1, wherein the polycaprolactone comprises from about 5 percent to about 95 percent by weight of the matrix.

7. The matrix of claim 1, wherein the polycaprolactone comprises from 25 percent to 75 percent by weight of the matrix.

8. An electrospun tubular composite matrix for use as a vascular construct comprising 25% to 75% of electrospun polycaprolactone and at least one electrospun natural component, wherein the matrix has a three-dimensional ultrastructure of interconnected polycaprolactone and natural component fibers with an average diameter from 50 nanometers to 800 nanometers and pores to permit cell attachment and differentiation into a tissue layer and sufficient mechanical burst strength to withstand pressure up to 1,425 mmHg.

9. The matrix of claim 8 wherein the natural component further comprises collagen.

10. The matrix of claim 8, wherein the natural component comprises elastin.

11. The matrix of claim 8, wherein the natural component comprises both collagen and elastin.

12. A method of preparing an electrospun tubular matrix for use as a vascular construct, comprising:

electrically charging a solution comprising polycaprolactone and at least one natural component; and

discharging the electrically charged solution onto a grounded target under an electrostatic field such that movement of the electrically charged solution under the electric field causes the electrically charged solution to evaporate and produce fibers of the matrix on the grounded target, wherein the matrix has a three-dimensional ultrastructure of interconnected polycaprolactone and natural component fibers with an average diameter from 50 nanometers to 800 nanometers and pores to permit cell attachment and differentiation into a tissue layer and sufficient mechanical burst strength to withstand pressure up to 1,425 mmHg.

13. The method of claim 12, wherein the step of discharging the electrically charged solution comprises discharging the solution at a voltage in the range of 15-30 kV.

14. The method of claim 12, wherein the grounded target is selected from the group consisting of a rotating drum, a rotating mandrel, and a planar surface.

15. The method of claim 12, wherein the grounded target is a rotating mandrel that rotates at least 500 revolutions per minute.

16. The method of claim 12, wherein the step of discharging the electrically charged solution is at a rate of 3 mL/hr.

17. The method of claim 12, wherein the method further comprises crosslinking the matrix.

18. The method of claim 17, wherein the step of crosslinking comprises crosslinking the matrix with a glutaraldehyde solution.