# US 11,077,138 B2 · Methods of tissue repair and regeneration > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 11,077,138 B2 - Document ID: US11077138B2 - Status: Granted - Kind: B2 - Application number: 15/568,386 - Filed: 2016-04-08 - Published: 2018-04-12 - Granted: 2021-08-03 - Earliest claimed: 2015-04-22 - Assignees: Innolife Co., Ltd. - Applicants: Innolife Co., Ltd. - Inventors: Yujian James Kang - Web page: https://patentgrep.com/patent/US11077138B2 ## CPC - A61K 33/34: Copper; Compounds thereof - A61K 9/0009: {involving or responsive to electricity, magnetism or acoustic waves; Galenical aspects of sonophoresis, iontophoresis, electroporation or electroosmosis} - A61K 9/0019: {Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00)} - A61K 9/5052: {Proteins, e.g. albumin} - A61K 33/04: Sulfur, selenium or tellurium; Compounds thereof - A61K 33/26: Iron; Compounds thereof - A61K 33/30: Zinc; Compounds thereof - A61K 35/12: Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells (vaccines or medicinal preparations containing antigens or antibodies A61K39/00) - A61P 9/10: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis - A61P 17/00: Drugs for dermatological disorders - A61P 17/02: for treating wounds, ulcers, burns, scars, keloids, or the like - A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 - 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 The disclosure provides local delivery of a trace element to a site of tissue injury, which triggers the body' inherent tissue repair mechanism. Local delivery of copper to the site of injury induces migration (i.e., homing) of stem cells to the site of injury, triggers differentiation of stem cells at the site of injury, induces tissue regeneration at the site of injury, induces signaling molecules that trigger tissue regeneration, reverses damage at the site of injury, and/or reconstructs the microenvironment of neurofibril cells and neurosecretory cells at the site of injury. In another aspect, delivering a trace element (for example, copper) directly to the site of injury and associated methods are disclosed. ## Claims ### Claim 1 A method of inducing at least two events of tissue repair in an individual having a tissue injury, comprising delivering to the site of injury an effective amount of copper, wherein the tissue is heart, liver or brain, wherein the at least two events of the tissue repair comprises inducing the migration of bone marrow mesenchymal stem cells to the site of injury, and at least one of: (i) inducing differentiation of stem cells at the site of injury; (ii) inducing tissue regeneration at the site of injury; (iii) inducing a signaling molecule that triggers tissue regeneration; and (iv) reconstruction of the microenvironment of neurofibril cells and neurosecretory cells at the site of injury. ### Claim 2 (depends on 1) The method of claim 1, wherein the tissue injury is an ischemic tissue injury. ### Claim 3 (depends on 1) The method of claim 1, further comprising administering to the individual an effective amount of stem cells. ### Claim 4 (depends on 1) The method of claim 1, further comprising delivering to the site of injury an effective amount of an inducer of stem cells. ### Claim 5 (depends on 1) The method of claim 1, wherein the individual has a compromised tissue repair system. ### Claim 6 (depends on 5) The method of claim 5, wherein the individual having a compromised tissue repair system is an individual having a chronic tissue injury. ### Claim 7 (depends on 5) The method of claim 5, wherein the individual having a compromised tissue repair system is an individual who is at least 60 years old. ### Claim 8 (depends on 5) The method of claim 5, wherein the individual having a compromised tissue repair system is an individual who is deficient in stem cells. ### Claim 9 (depends on 1) The method of claim 1, wherein copper is delivered via a microbubble. ### Claim 10 (depends on 9) The method of claim 9, wherein the microbubble comprising copper is administered intravenously, and copper is released through site-directed bursting of the microbubble at the site of the injury. ### Claim 11 (depends on 10) The method of claim 10, wherein the site-directed bursting of the microbubble is by ultrasound. ### Claim 12 (depends on 1) The method of claim 1, wherein copper is delivered by directly administering copper to the site of the injury. ### Claim 13 (depends on 1) The method of claim 1, wherein copper is delivered via injection and stays concentrated at the injection site upon injection. ### Claim 14 (depends on 1) The method of claim 1, wherein copper is delivered via an implant containing copper. ### Claim 15 (depends on 14) The method of claim 14, wherein the implant is coated with copper. ### Claim 16 (depends on 1) The method of claim 1, wherein the tissue injury is a chronic tissue injury. ### Claim 17 (depends on 16) The method of claim 16, wherein the tissue injury is an ischemic chronic tissue injury. ### Claim 18 (depends on 17) The method of claim 17, wherein the tissue is heart. ### Claim 19 (depends on 18) The method of claim 18, wherein copper is delivered via a microbubble. ### Claim 20 (depends on 19) The method of claim 19, wherein the individual has a myocardial infarction. ### Claim 21 (depends on 17) The method of claim 17, wherein the tissue is brain. ### Claim 22 (depends on 21) The method of claim 21, wherein the individual has a cerebral infarction.