IP Library Granted Patent US 11,497,830
Granted Patent B2
US 11,497,830 · App. 15/125,749 · Granted Nov 15, 2022

Electrospinning of cartilage and meniscus matrix polymers

Inventors: Darryl D. D'Lima (San Diego, CA); Shawn Grogan (Mission Viejo, CA); Clifford W. Colwell, Jr. (La Jolla, CA); Jihye Baek (San Diego, CA)
Assignee: SCRIPPS HEALTH
A61L27/26A61F2/3094A61F2/30756A61F2/3872A61L27/18A61L27/20A61L27/24A61L27/3817A61L27/3826A61L27/3834A61L27/50A61L27/52A61L27/54A61L27/58D01D5/0038D01D5/34A61F2002/4495A61F2210/0004A61L2300/414A61L2430/06D10B2331/041D10B2401/12D10B2509/00
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Quick Facts
Patent No.
US 11,497,830
App. No.
15/125,749
Granted
Nov 15, 2022
Kind
B2
Abstract

Disclosed herein are methods of producing a cartilaginous implant by producing a polymer scaffold composition by electrospinning a polymer solution onto a collector in order to obtain polymer fibers; crosslinking the polymer fibers; and adding a plurality of cells to the polymer scaffold composition, wherein the plurality of cells comprises cartilaginous cells to form a cartilaginous implant.

Claims (50)

1. A method of producing a meniscal implant, the method comprising:

a) forming polymer fibers by electrospinning a first polymer solution comprising a first polymer and a second polymer solution comprising a second polymer, the electrospinning comprising:

i) applying a first voltage to the first polymer solution in a first emitter and ejecting the first polymer solution through a first emitter outlet; and

ii) applying a second voltage to the second polymer solution in a second emitter and ejecting the second polymer solution through a second emitter outlet,

wherein the electrospinning the first polymer solution and the second polymer solution occurs simultaneously;

b) collecting the polymer fibers onto a rotating collector;

c) electrospraying a plurality of cells onto the rotating collector and the polymer fibers; and

d) crosslinking the polymer fibers to produce the meniscal implant,

wherein the electrospinning and the electrospraying occur before the crosslinking,

wherein the rotating collector comprises a V shape or a custom shape of meniscus,

wherein the meniscal implant comprises the V shape or the custom shape of meniscus, and

wherein the meniscal implant has a Young's modulus of about 100 MPa to about 300 MPa measured in a circumferential direction.

2. The method of claim 1 , wherein the first polymer, the second polymer, or both, is selected from the group consisting of: polylactic acid, collagen, methacrylated collagen, and combinations thereof.

3. The method of claim 1 , wherein the electrospinning the first polymer solution produces a first plurality of polymer fibers on the rotating collector and wherein the second polymer solution produces a second plurality of polymer fibers on the rotating collector.

4. The method of claim 1 , wherein the first emitter outlet comprises a first tube with a first interior and the second emitter outlet comprises a second tube with a second interior, wherein the second tube is within the first interior of the first tube, and the first tube and the second tube are co-axial.

5. The method of claim 4 , wherein the first polymer solution encapsulates the second polymer solution as they are ejected from the emitter outlets onto the rotating collector to form the polymer fibers, wherein the polymer fibers have a structure comprising:

a) a shell comprising the first polymer; and

b) a core comprising the second polymer.

6. The method of claim 5 , wherein the first polymer is selected from the group consisting of: collagen, methacrylated collagen, and both.

7. The method of claim 5 , wherein the second polymer is selected from the group consisting of: polylactic acid, polycaprolactone, a copolymer thereof, and a blend thereof.

8. The method of claim 1 , further comprising applying a voltage to the rotating collector.

9. The method of claim 1 , wherein the electrospinning and the electrospraying occur simultaneously.

10. The method of claim 1 , wherein the plurality of cells is selected from the group consisting of: chondrocytes, cartilaginous cells, fibrocartilaginous cells, chondroblasts, meniscal cells, and progenitors thereof.

11. The method of claim 1 , wherein the plurality of cells is selected from the group consisting of: mesenchymal stem cells, meniscal cells, chondroblasts, chondrocytes, and a combination thereof.

12. The method of claim 1 , further comprising contacting the meniscal implant with a biomimetic gel.

13. The method of claim 1 , further comprising producing a plurality of meniscal implants.

14. The method of claim 1 , further comprising combining a plurality of the polymer fibers to form a multilayer meniscal implant.

15. The method of claim 1 , wherein the crosslinking the polymer fibers comprises photocrosslinking.

16. The method of claim 8 , wherein a voltage differential between the voltage applied to the rotating collector and the voltage applied to the first or second polymer ranges from about 10 kV to about 30 kV.

17. A method of producing a meniscal implant, the method comprising:

a) forming polymer fibers by electrospinning a first polymer solution comprising a first polymer and a second polymer solution comprising a second polymer to form the polymer fibers, the electrospinning comprising:

i) applying a first voltage to the first polymer solution in a first emitter and ejecting the first polymer solution through a first emitter outlet; and

ii) applying a second voltage to the second polymer solution in a second emitter and ejecting the second polymer solution through a second emitter outlet,

wherein the electrospinning the first polymer solution and the second polymer solution occurs simultaneously;

b) collecting the polymer fibers onto a rotating collector;

c) crosslinking the polymer fibers to produce the meniscal implant; and

d) electrospraying a plurality of cells onto the rotating collector and the polymer fibers;

wherein the electrospinning, the crosslinking, and the electrospraying occur simultaneously,

wherein the rotating collector comprises a V shape or a custom shape of meniscus,

wherein the meniscal implant comprises the V shape or the custom shape of meniscus, and

wherein the meniscal implant has a Young's modulus of about 100 MPa to about 300 MPa measured in a circumferential direction.

18. The method of claim 17 , wherein the electrospinning the first polymer solution and the second polymer solution comprises co-axial electrospinning, wherein the first polymer solution surrounds the second polymer solution as they are ejected from the emitter outlets onto the rotating collector to form the polymer fibers, wherein the polymer fibers have a structure comprising:

a) a shell comprising the first polymer; and

b) a core comprising the second polymer.

19. The method of claim 1 , further comprising crosslinking the polymer fibers intermittently.

20. The method of claim 1 , further comprising rotating the rotating collector.

21. The method of claim 20 , wherein the rotating comprises rotating the rotating collector at a constant speed.

22. The method of claim 20 , wherein the rotating collector comprises a drum collector.

23. The method of claim 10 , wherein the plurality of cells comprises meniscal cells.

24. The method of claim 20 , wherein the rotating comprises rotating the rotating collector at an alternating speed.

Assignments (3)
CORRECTIVE ASSIGNMENT TO CORRECT THE FIRST INVENTORS NAME PREVIOUSLY RECORDED AT REEL: 040049 FRAME: 0455. ASSIGNOR(S) HEREBY CONFIRMS THE ASSIGNMENT. Recorded Feb 22, 2021
From: D'LIMA, DARRYL D.; GROGAN, SHAWN; COLWELL, CLIFFORD W., JR.
To: SCRIPPS HEALTH
Reel/Frame 055362/0178 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 4, 2017
From: BAEK, JIHYE
To: SCRIPPS HEALTH
Reel/Frame 043454/0905 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 18, 2016
From: D'LIMA, DARRYL; GROGAN, SHAWN; COLWELL, CLIFFORD W., JR.
To: SCRIPPS HEALTH
Reel/Frame 040049/0455 →
Continuity (3)
Provisional Application 61955082 · Mar 18, 2014
Provisional Application 61953550 · Mar 14, 2014
Related Publication 20170007741A1 · Jan 12, 2017