# US 10,869,952 B2 · Tissue grafts modified with a cross-linking agent and method of making and 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 10,869,952 B2 - Document ID: US10869952B2 - Status: Granted - Kind: B2 - Application number: 16/260,738 - Filed: 2019-01-29 - Published: 2019-06-13 - Granted: 2020-12-22 - Earliest claimed: 2011-02-14 - Assignees: MiMedx Group, Inc. - Applicants: MiMedx Group, Inc. - Inventors: Brenda S. Morse; Somaly Sith; Randall Spencer; John Daniel - Web page: https://patentgrep.com/patent/US10869952B2 ## 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} - A61K 35/50: Placenta; Placental stem cells; Amniotic fluid; Amnion; Amniotic stem cells - A61L 27/3687: {characterised by the use of chemical agents in the treatment, e.g. specific enzymes, detergents, capping agents, crosslinkers, anticalcification agents} - A61P 17/02: for treating wounds, ulcers, burns, scars, keloids, or the like - A61P 19/00: Drugs for skeletal disorders - A61P 41/00: Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution - 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) - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS ## Abstract Described herein are tissue grafts derived from the placenta that possess good adhesion to biological tissues and are useful in would healing applications. In one aspect, the tissue graft includes (1) two or more layers of amnion, wherein at least one layer of amnion is cross-linked, (2) two or more layers of chorion, wherein at least one layer of amnion is cross-linked, or (3) one or more layers of amnion and chorion, wherein at least one layer of amnion and/or chorion is cross-linked. In another aspect, the grafts are composed of amnion and chorion cross-linked with one another. In a further aspect, the grafts have one or more layers sandwiched between the amnion and chorion membranes. The amnion and/or the chorion are treated with a cross-linking agent prior to the formation of the graft. The presence of the cross-linking agent present on the graft also enhances adhesion to the biological tissue of interest. Also described herein are methods for making and using the tissue grafts. ## Claims ### Claim 1 A method for enhancing adhesion of a tissue graft to a biological tissue of a patient, said method comprising applying a tissue graft to said biological tissue of a patient, wherein said tissue graft comprises at least two layers of placental tissue, wherein said at least two layers of placental tissue comprise two or more layers of chorion, wherein at least one layer of chorion is treated with a cross-linking agent and comprises a cross-linking group; wherein one or more of said cross-linking groups forms a covalent bond with said biological tissue, thereby enhancing adhesion of the tissue graft to the biological tissue; wherein at least one layer of placental tissue has not been treated with a cross-linking agent; and wherein the tissue graft is not decellularized. ### Claim 2 (depends on 1) The method of claim 1, wherein more than one layer of placental tissue is treated with a cross-linking agent and comprises a cross-linking group, and the placental tissue layers are treated with the same cross-linking agent. ### Claim 3 (depends on 1) The method of claim 1, wherein more than one layer of placental tissue is treated with a cross-linking agent and comprises a cross-linking group, and the placental tissue layers are treated with different cross-linking agents. ### Claim 4 (depends on 1) The method of claim 1, wherein the cross-linking agent comprises a sugar, a dialdehyde, a carbodiimide, or a combination thereof. ### Claim 5 (depends on 4) The method of claim 4, wherein the sugar comprises D-ribose, glycerose, altrose, talose, ertheose, glucose, lyxose, mannose, xylose, gulose, arabinose, idose, allose, galactose, maltose, lactose, sucrose, cellibiose, gentibiose, melibiose, turanose, trehalose, isomaltose, or any combination thereof. ### Claim 6 (depends on 1) The method of claim 1, wherein the tissue graft includes an embossed texture or design. ### Claim 7 (depends on 1) The method of claim 1, wherein the tissue graft comprises one or more additional membranes treated with a cross-linking agent. ### Claim 8 (depends on 7) The method of claim 7, wherein the one or more additional membranes comprise amnion, chorion, allograft pericardium, allograft acellular dermis, amniotic membrane, Wharton's jelly, purified xenograft Type-1 collagen, biocellulose polymers or copolymers, biocompatible synthetic polymer or copolymer films, purified small intestinal submucosa, bladder acellular matrix, cadaveric fascia, or any combination thereof. ### Claim 9 (depends on 7) The method of claim 7, wherein the one or more additional membranes comprise an amnion membrane. ### Claim 10 (depends on 1) The method of claim 1, wherein the biological tissue comprises a wound and said tissue graft is a wound dressing. ### Claim 11 (depends on 1) The method of claim 1, wherein the biological tissue is the spinal dura of the patient or a region near the spine, and the tissue graft is applied after a surgical procedure to prevent or reduce scar formation on or near the spine. ### Claim 12 (depends on 11) The method of claim 11, wherein the surgical procedure comprises a posterior procedure. ### Claim 13 (depends on 12) The method of claim 12, wherein the posterior procedure is a laminectomy, discectomy, a Posterior Lumbar Interbody Fusion, or a Transforaminal Lumbar Interbody Fusion. ### Claim 14 (depends on 11) The method of claim 11, wherein the surgical procedure comprises an anterior procedure. ### Claim 15 (depends on 1) The method of claim 1, wherein the tissue graft is applied to the biological tissue without the use of a suture. ### Claim 16 (depends on 1) The method of claim 1, wherein the biological tissue is the spinal dura of the patient, and the tissue graft is applied after a dural tear. ### Claim 17 (depends on 1) The method of claim 1, wherein the biological tissue comprises a wound and the tissue graft is applied to the wound, wherein the wound is in the cranial dura, a wound resulting from a perioplastic procedure, a frenum pull, lost patella tissue, associated with the Schneiderian membrane in the sinus cavity, or associated with the soft tissue around dental implants, wherein the tissue graft promotes healing of the wound. ### Claim 18 (depends on 1) The method of claim 1, wherein the biological tissue comprises a wound associated with a dental surgical procedure, an orthopedic application, an ENT application, a gynecological application, an urological application, or general surgery, or wherein the biological tissue comprises an extremity having a wound, or wherein the biological tissue comprises an eye.