Nerve grafts containing regenerative compounds, methods of making the same, and methods of treatment using the same

Patent metadata

Field	Value
Publication number	US-12576189-B2
Application number	US-202218068715-A
Country	US
Kind code	B2
Filing date	Dec 20, 2022
Priority date	Dec 22, 2021
Publication date	Mar 17, 2026
Grant date	Mar 17, 2026

Abstract

A method of preparing a nerve graft includes submerging a nerve graft in a solution including FK506 and a solvent to promote incorporation of FK506 into the nerve graft. A tissue graft includes nerve tissue and FK506 incorporated within the nerve tissue. In the tissue graft, the FK506 is free of hydrogel and not encapsulated.

First claim

What is claimed is:

1 . A method of preparing a nerve graft, the method comprising: submerging a nerve graft comprising acellular nerve tissue with hydrophobic portions in a solution comprising FK506 and a solvent that comprises between about 1% and about 15% by volume dimethyl sulfoxide (DMSO) to promote incorporation of FK506 into the nerve graft, the solution being free of polymer.

2 . The method of claim 1 , wherein the solution comprises between about 1 pg/mL to about 50 mg/mL FK506.

3 . The method of claim 1 , wherein the solution comprises one or more soluble salts of: sodium, potassium, calcium, magnesium, or other monovalent or divalent metal cationic salts.

4 . A method of preparing a nerve graft, the method comprising:
submerging a nerve graft comprising acellular nerve tissue with hydrophobic portions in a solution comprising FK506 and a solvent to promote incorporation of FK506 into the nerve graft, the solution being free of polymer; and sterilizing the nerve graft by exposing the nerve graft to gamma irradiation.

5 . The method of claim 4 , wherein sterilizing the nerve graft is performed while the nerve graft is in the solution.

6 . The method of claim 1 , wherein the nerve graft is in the solution for a period of at least one day.

7 . The method of claim 1 , wherein the nerve graft is in the solution for a period of at least one week.

8 . A method of preparing a nerve graft, the method comprising:
exposing a nerve graft comprising acellular nerve tissue with hydrophobic portions to a solution comprising FK506, while the nerve graft is within a container, such that the FK506 is at least partially incorporated within one or more of the hydrophobic portions of the nerve graft such that the FK506 is present in greater concentrations within the one or more hydrophobic portions as compared to a non-hydrophobic portion of the acellular nerve tissue; sterilizing the nerve graft while the nerve graft and the solution are within the container; and storing the nerve graft and the solution in the container.

9 . The method of claim 8 , wherein storing the nerve graft is performed at room temperature for a period of at least one day.

10 . The method of claim 8 , wherein the nerve graft has a diameter of between about 0.5 mm and about 8 mm.

11 . The method of claim 8 , wherein the nerve graft and the solution are contained within wet-preservation packaging that forms the container for a period of time sufficient to allow the FK506 to become fully incorporated in the nerve graft.

12 . The method of claim 11 , wherein the nerve graft and the solution are exposed to gamma irradiation while being contained within the packaging.

13 . The method of claim 8 , wherein the nerve graft is placed in the solution for a period of time sufficient for a concentration of FK506 within the nerve graft to reach a steady-state.

14 . A method of preparing a nerve graft, the method comprising:
submerging a nerve graft that includes acellular nerve tissue with hydrophobic portions in a solution, the solution comprising FK506 and DMSO and being free of polymer, to promote incorporation of FK506 throughout the nerve tissue of the nerve graft such that the FK506 is present in greater concentrations within the hydrophobic portions as compared to a non-hydrophobic portion of the acellular nerve tissue.

15 . The method of claim 14 , wherein, after the submerging, the FK506 is incorporated throughout an entirety of the nerve tissue of the nerve graft.

16 . The method of claim 14 , wherein incorporation of the FK506 occurs at least in part during storage or distribution of the nerve graft while the nerve graft is contained in a sealed packaging.

17 . The method of claim 14 , wherein, following the submerging, the FK506 is fully incorporated in the nerve tissue of the nerve graft.

18 . The method of claim 14 , wherein the solution contains less than about 15% DMSO by volume of the solution.

19 . The method of claim 1 , wherein the nerve graft comprises acellular nerve tissue having a structure that corresponds to at least one of perineurium or endoneurium, the FK506 being present inside the structure.

20 . The method of claim 8 , wherein the nerve graft comprises acellular nerve tissue having a structure that corresponds to at least one of perineurium or endoneurium, the FK506 being present inside the structure.

Assignees

• Axogen Corp

Inventors

• Tajdaran Kasra
• Scopelianos Angelo

Classifications

• A61L27/22

  Polypeptides or derivatives thereof {, e.g. degradation products} · CPC title

• A61L27/02

  Inorganic materials · CPC title

• A61L27/3675

  Nerve tissue, e.g. brain, spinal cord, nerves, dura mater · CPC title

• A61L2300/426

  Immunomodulating agents, i.e. cytokines, interleukins, interferons · CPC title

• A61L2430/40

  Preparation and treatment of biological tissue for implantation, e.g. decellularisation, cross-linking · CPC title