# US 11,998,661 B2 · Fasciculated nerve grafts, methods of making the same, and methods of treatment using the same > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 11,998,661 B2 - Document ID: US11998661B2 - Status: Granted - Kind: B2 - Application number: 17/451,489 - Filed: 2021-10-20 - Published: 2022-04-28 - Granted: 2024-06-04 - Earliest claimed: 2020-10-22 - Assignees: Axogen Corporation - Applicants: Axogen Corporation - Inventors: Jennifer Faleris; Kasra Tajdaran - Web page: https://patentgrep.com/patent/US11998661B2 ## CPC - A61L 27/3604: {characterised by the human or animal origin of the biological material, e.g. hair, fascia, fish scales, silk, shellac, pericardium, pleura, renal tissue, amniotic membrane, parenchymal tissue, fetal tissue, muscle tissue, fat tissue, enamel} - A61L 27/3878: {Nerve tissue, brain, spinal cord, nerves, dura mater} - A61L 27/20: Polysaccharides - A61L 27/222: {Gelatin} - A61L 27/225: {Fibrin; Fibrinogen} - A61L 27/227: {Other specific proteins or polypeptides not covered by A61L27/222, A61L27/225 or A61L27/24} - A61L 27/24: Collagen - A61L 27/3675: {Nerve tissue, e.g. brain, spinal cord, nerves, dura mater} - A61L 27/3687: {characterised by the use of chemical agents in the treatment, e.g. specific enzymes, detergents, capping agents, crosslinkers, anticalcification agents} - A61L 27/3691: {characterised by physical conditions of the treatment, e.g. applying a compressive force to the composition, pressure cycles, ultrasonic/sonication or microwave treatment, lyophilisation} - A61L 27/44: having a macromolecular matrix - A61L 27/52: Hydrogels or hydrocolloids - A61L 27/54: Biologically active materials, e.g. therapeutic substances {(A61L27/227 takes precedence)} - A61L 27/58: Materials at least partially resorbable by the body - A61L 2300/41: Anti-inflammatory agents, e.g. NSAIDs - A61L 2300/414: Growth factors - A61L 2300/426: Immunomodulating agents, i.e. cytokines, interleukins, interferons - A61L 2300/64: Animal cells - A61L 2430/32: for nerve reconstruction - A61L 2430/40: Preparation and treatment of biological tissue for implantation, e.g. decellularisation, cross-linking - A61L: METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES (preservation of bodies or disinfecting characterised by the agents employed A01N; preserving, e.g. sterilising, food or foodstuffs A23; preparations for medical, dental or toiletry purposes A61K) ## Abstract The present disclosure provides fasciculated nerve grafts of customizable lengths and diameters, and methods of preparing the same. The grafts are made by digesting native extracellular matrix (ECM) around the nerve fascicles of a nerve tissue, and the epineurial sheath. One or more of the individual fascicles may then be entubulated in an entubulation material, embedded in or coated with a coating material, or both, to form a fasciculated nerve graft. The fasciculated nerve grafts are customizable and designed to bridge nerve gaps; the modularity of the fasciculated nerve graft allows for restoring continuity to nerve defects of virtually any length and allows for matching the diameter of the patient's recipient nerve. ## Claims ### Claim 1 A fasciculated nerve graft comprising: one or more nerve fascicles; and an entubulation material comprising a biocompatible material, the entubulation material entubulating the one or more nerve fascicles, wherein the fasciculated nerve graft is substantially free of epineurial sheath and of native extracellular matrix material. ### Claim 2 (depends on 1) The fasciculated nerve graft of claim 1, comprising a single nerve fascicle. ### Claim 3 (depends on 1) The fasciculated nerve graft of claim 1, comprising two or more nerve fascicles. ### Claim 4 (depends on 3) The fasciculated nerve graft of claim 3, comprising 2 nerve fascicles to 20 nerve fascicles. ### Claim 5 (depends on 3) The fasciculated nerve graft of claim 3, wherein the fasciculated nerve graft comprises nerve fascicles that are substantially similar to one another in diameter. ### Claim 6 (depends on 5) The fasciculated nerve graft of claim 5, wherein a diameter of each of the nerve fascicles is between about 50 μm and about 1 mm. ### Claim 7 (depends on 1) The fasciculated nerve of graft of claim 1, wherein the fasciculated nerve graft has a diameter of between about 50 μm and about 1 mm. ### Claim 8 (depends on 3) The fasciculated nerve graft of claim 3, wherein the fasciculated nerve graft comprises nerve fascicles that are substantially similar to one another in length. ### Claim 9 (depends on 1) The fasciculated nerve graft of claim 1, wherein the fasciculated nerve graft has a length of between about 3 mm and about 200 mm. ### Claim 10 (depends on 1) The fasciculated nerve graft of claim 1, wherein the one or more nerve fascicles are embedded in or coated with a coating material comprising a biocompatible material. ### Claim 11 (depends on 10) The fasciculated nerve graft of claim 10, wherein the biocompatible material of one or both of the entubulation material or the coating material is biodegradable. ### Claim 12 (depends on 10) The fasciculated nerve graft of claim 10, wherein the biocompatible material of one or both of the entubulation material and the coating material is an extracellular matrix material comprising one or more of a collagen, a chitosan, an alginate, a biodegradable polymer, a cellulose, a fibrinogen, a fibrin, a protein-based polymer, a gelatin, a polysaccharide, a hydrogel, or a non-native extracellular matrix material. ### Claim 13 (depends on 1) The fasciculated nerve graft of claim 1, wherein a gel, a collagen, a gelatin, a polysaccharide, a hydrogel, a fibrin, a fibrinogen, an alginate, or a non-native extracellular matrix material is also surrounded by the entubulation material. ### Claim 14 (depends on 1) The fasciculated nerve graft of claim 1, wherein the entubulation material comprises a seam and the seam is sealed by a biocompatible adhesive or sealant. ### Claim 15 (depends on 1) The fasciculated nerve graft of claim 1, wherein the one or more nerve fascicles are from a human, a non-human animal, or both. ### Claim 16 (depends on 1) The fasciculated nerve graft of claim 1, wherein the fasciculated nerve graft further comprises one or more of a growth factor, a cell, a mix of cells including multiple cell types in a mixed cell population, a cellular component, a non-steroidal anti-inflammatory agent, or an immunosuppressive agent. ### Claim 17 (depends on 1) The fasciculated nerve graft of claim 1, wherein the fasciculated nerve graft is a peripheral nerve graft or a spinal nerve graft. ### Claim 18 (depends on 1) The fasciculated nerve graft of claim 1, wherein at least about 50%, at least about 85%, at least about 95%, at least about 99%, or the entirety of the native extracellular matrix material has been removed. ### Claim 19 (depends on 1) The fasciculated nerve graft of claim 1, wherein at least about 95%, at least about 99%, or the entirety of the epineurial sheath has been removed. ### Claim 20 (depends on 1) The fasciculated nerve graft of claim 1, wherein about 50%, about 85%, about 95%, about 99%, or the entirety of the native extracellular matrix material has been removed. ### Claim 21 (depends on 1) The fasciculated nerve graft of claim 1, wherein about 95%, about 99%, or the entirety of the epineurial sheath has been removed. ### Claim 22 A fasciculated nerve graft prepared according to a method comprising: treating a nerve tissue with one or more enzymes to at least partially degrade epineurial sheath and native extracellular matrix (ECM) material of the nerve tissue; washing the treated nerve tissue to remove the one or more enzymes and debris, thereby producing one or more nerve fascicles that are substantially free of epineurial sheath and native ECM material; and entubulating the one or more nerve fascicles in an entubulation material comprising a biocompatible material.