IP Library Granted Patent US 12,178,943
Granted Patent B2
US 12,178,943 · App. 17/184,231 · Granted Dec 31, 2024

Compositions and materials for regeneration of skeletal muscle

Inventors: Meng Deng (West Lafayette, IN); Naagarajan Narayanan (Boulder, CO); Shihuan Kuang (West Lafayette, IN)
A61L31/145C07K14/47C12N5/0618
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Quick Facts
Patent No.
US 12,178,943
App. No.
17/184,231
Granted
Dec 31, 2024
Kind
B2
Abstract

A composition for regeneration of skeletal muscle includes a nerve cell secretome or an isolate thereof. An implantable therapeutic material for regeneration of skeletal muscle includes a hydrogel and nerve cells encapsulated within the hydrogel, wherein at least some of the nerve cells are living. A method of regenerating skeletal muscle includes applying the composition or implanting the implantable material adjacent to skeletal muscle myoblasts and/or myogenic cells to regenerate skeletal muscle therefrom.

Claims (28)

1. A medical implant comprising:

an implantable therapeutic material for regeneration of skeletal muscle comprising

a hydrogel comprising a reaction product of a composition comprising hyaluronic acid, chondroitin sulfate, and polyethylene glycol or a copolymer thereof, wherein the hydrogel is injectable and has a storage modulus of 10 kPa to 16 kPa, and

nerve cells encapsulated within the hydrogel, wherein at least some of the nerve cells are living; and

a fiber scaffold in contact with the implantable therapeutic material, wherein the fiber scaffold is an aligned electrospun fiber scaffold that is a fiber mat, and wherein the fiber scaffold comprises skeletal muscle myoblasts and/or myogenic cells.

2. The medical implant of claim 1 , wherein the hydrogel is a 3D matrix that encapsulates the nerve cells.

3. The medical implant of claim 1 , wherein the nerve cells comprise a unipolar nerve cell, a bipolar nerve cell, a multipolar nerve cell, an anaxonic nerve cell, a pseudounipolar nerve cell, a basket nerve cell, a Betz nerve cell, a Lugaro nerve cell, a medium spiny nerve cell, a Purkinje nerve cell, a Renshaw nerve cell, a unipolar brush nerve cell, a granule nerve cell, an anterior horn nerve cell, a spindle nerve cell, an afferent nerve cell, an efferent nerve cell, an interneuron nerve cell, a cholinergic nerve cell, an adrenergic nerve cell, a GABAergic nerve cell, a glutamatergic nerve cell, a dopaminergic nerve cell, a serotonergic nerve cell, a purinergic nerve cell, a histaminergic nerve cell, a catecholamine nerve cell, or a combination thereof.

4. The medical implant of claim 1 , wherein the nerve cells comprise a catecholamine nerve cell.

5. The medical implant of claim 1 , wherein the nerve cells comprise an adrenal pheochromocytoma PC12 cell line.

6. The medical implant of claim 1 , wherein the nerve cells encapsulated within the hydrogel release a nerve cell secretome such that the hydrogel releases the secretome.

7. The medical implant of claim 6 , wherein the secretome comprises Galectin-1, Progranulin, CathepsinB, Glypican-1, Prosaposin, or a combination thereof.

8. The medical implant of claim 1 , wherein the composition comprising hyaluronic acid, chondroitin sulfate, and polyethylene glycol or a copolymer thereof further comprises polyvinyl alcohol, sodium polyacrylate, an acrylate polymer, an acrylate copolymer, polylactic acid, a polylactic acid copolymer, polyglycolic acid, a polyglycolic acid copolymer, poly(lactic-co-glycolic acid), poly(amino acids), polyphosphazenes, poly(phosphoesters), collagen, gelatin, fibrin, agarose, chitosan, cellulose, a cellulose derivative, methylcellulose, elastin, dextran, agarose, alginate, heparin, an elastin-like-polypeptide (ELP), or a combination thereof.

9. The medical implant of claim 1 , wherein the hydrogel has a storage modulus of 11 kPa to 16 kPa.

10. The medical implant of claim 1 , wherein the hydrogel has a storage modulus of 11.5 kPa to 16 kPa.

11. The medical implant of claim 1 , wherein the fiber scaffold comprises polyester, poly(lactide-co-glycolide), or a combination thereof.

12. The medical implant of claim 1 , wherein at least some of the skeletal muscle myoblasts and/or myogenic cells are added to and/or cultured on the fiber scaffold prior to implantation of the medical implant.

13. The medical implant of claim 1 , wherein the aligned electrospun fiber scaffold is formed by a method comprising collecting electrospun fibers on a rotating drum.

14. The medical implant of claim 1 , wherein the hydrogel comprises an interconnected, microporous structure.

15. A method of forming the medical implant of claim 1 , the method comprising:

adding the nerve cells to a hydrogel precursor composition;

forming the hydrogel from the hydrogel precursor composition to form the implantable therapeutic material; and

contacting the implantable therapeutic material with a fiber scaffold comprising skeletal muscle myoblasts and/or myogenic cells to form the medical implant.

16. A method of regenerating skeletal muscle, the method comprising:

implanting the medical implant of claim 1 adjacent to skeletal muscle myoblasts and/or myogenic cells to regenerate skeletal muscle therefrom.

17. A method of regenerating skeletal muscle, the method comprising:

implanting a medical implant adjacent to skeletal muscle myoblasts and/or myogenic cells to regenerate skeletal muscle therefrom, the medical implant comprising

an implantable therapeutic material for the regeneration of skeletal muscle comprising a hydrogel and nerve cells encapsulated within the hydrogel, wherein at least some of the nerve cells are living, wherein the nerve cells encapsulated within the hydrogel release a nerve cell secretome such that the hydrogel releases the secretome, and wherein the hydrogel is injectable and has a storage modulus of 10 kPa to 16 kPa, and

a fiber scaffold in contact with the implantable therapeutic material, wherein the fiber scaffold is an aligned electrospun fiber scaffold that is a fiber mat.

Assignments (2)
CONFIRMATORY LICENSE Recorded Nov 2, 2023
From: PURDUE UNIVERSITY
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 065431/0428 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 21, 2021
From: KUANG, SHIHUAN; DENG, MENG; NARAYANAN, NAAGARAJAN
To: PURDUE RESEARCH FOUNDATION
Reel/Frame 055987/0633 →
Continuity (2)
Provisional Application 63016386 · Apr 28, 2020
Related Publication 20210330870A1 · Oct 28, 2021