# US 2014/0155680 A1 · Angiogenesis initiation and growth > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2014/0155680 A1 - Document ID: US20140155680A1 - Status: Published application - Kind: A1 - Application number: 14/172,418 - Filed: 2014-02-04 - Published: 2014-06-05 - Earliest claimed: 2007-03-06 - Assignees: Biomet Biologics, LLC - Applicants: Biomet Biologics, LLC - Inventors: Joel C. HIGGINS; Bruce SIMON; Jennifer E. WOODELL-MAY - Web page: https://patentgrep.com/patent/US20140155680A1 ## CPC - A61K 35/19: Platelets; Megacaryocytes - A61K 35/16: Blood plasma; Blood serum (umbilical cord blood A61K35/51) - A61K 35/28: Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells - A61K 35/35: Fat tissue; Adipocytes; Stromal cells; Connective tissues (adipose-derived stem cells A61K35/28; collagen A61K38/39) - A61K 38/18: Growth factors; Growth regulators - A61K 38/19: Cytokines; Lymphokines; Interferons - A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca - A61M 37/00: Other apparatus for introducing media into the body (for reproduction or fertilisation A61B17/425; apparatus for iontophoresis or cataphoresis A61N1/30); Percutany, i.e. introducing medicines into the body by diffusion through the skin (salt baths A61H33/04) - A61N 1/205: {for promoting a biological process} - A61N 1/326: {for promoting growth of cells, e.g. bone cells} - A61N 2/02: using magnetic fields produced by coils, including single turn loops or electromagnets (A61N2/12 takes precedence) - C12N 13/00: Treatment of microorganisms or enzymes with electrical or wave energy, e.g. magnetism, sonic waves - 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) - A61M: DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY (introducing media into or onto the bodies of animals A61D7/00; means for inserting tampons A61F13/26; devices for administering food or medicines orally A61J; containers for collecting, storing or administering blood or medical fluids A61J1/05); DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY (surgery A61B; chemical aspects of surgical articles A61L); DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR {(Electrotherapy, e.g. producing anaesthesia by the use of alternating or intermittent currents A61N1/36021)} - A61N: ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY (measurement of bioelectric currents A61B; surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body A61B18/00; anaesthetic apparatus in general A61M; incandescent lamps H01K; infrared radiators for heating H05B) - C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00) ## Abstract Methods for promoting angiogenesis comprising administering platelet-rich plasma to a site and stimulating the site with an electromagnetic field. Platelets include platelet-rich plasma and compositions can further include stem cells such as adipose stromal cells and cells derived from bone marrow aspirate. Methods also comprise isolating platelets from a patient's blood, forming a composition including the platelets, delivering the composition to a site in need of treatment, and electrically stimulating the site. ## Claims ### Claim at position 1 1-12. (canceled) ### Claim 13 A method for promoting angiogenesis at a site on a patient, the method comprising: obtaining blood compatible with the patient; isolating platelet-rich plasma; administering said platelet-rich plasma to the site; and stimulating the site with an electromagnetic field following administration of said platelet-rich plasma to the site; thereby promoting angiogenesis at the site upon application of said electromagnetic field and said platelet-rich plasma to the site. ### Claim 14 (depends on 13) The method for promoting angiogenesis at a site on a patient as set forth in claim 13, wherein the isolating of the platelet-rich plasma comprises density fractionation of said blood, and the stimulating of the site with an electromagnetic field comprises generating in the tissue a capacitively-coupled time-varying electromagnetic field, or generating a pulsed electromagnetic field. ### Claim 15 (depends on 13) The method for promoting angiogenesis at a site on a patient as set forth in claim 13, wherein the density fractionation comprises centrifugation, and the stimulating of the site with the electromagnetic field comprises generating in the tissue a capacitively-coupled time-varying electromagnetic field having a peak amplitude of from about 0.1 to about 100 millivolts per centimeter, and having a frequency from about 1 kHz to about 200 kHz. ### Claim 16 (depends on 13) The method for promoting angiogenesis at the site on a patient as set forth in claim 13, wherein the density fractionation comprises centrifugation, and the stimulating of the site with an electromagnetic field comprises generating a pulsed electromagnetic field having a pulse duration from about 10 to 2000 microseconds. ### Claim 17 (depends on 14) The method for promoting angiogenesis at a site on a patient as set forth in claim 14, wherein the stimulating of the site with an electromagnetic field comprises: placing at least two electrodes across the site on the patient; and applying electrical energy to said electrodes so as to capacitively couple said electrodes and generate said electromagnetic field therebetween, said electromagnetic field passing through said platelet-rich plasma so as to promote angiogenesis at the site. ### Claim 18 (depends on 14) The method for promoting angiogenesis at a site on a patient as set forth in claim 14, wherein the stimulating of the site with an electromagnetic field comprises: placing a stimulation coil proximate to the site; and generating a pulsed electromagnetic field at the site by said stimulation coil, said pulsed electromagnetic field passing through said platelet-rich plasma so as to promote angiogenesis at the site. ### Claim 19 (depends on 13) The method for promoting angiogenesis at a site on a patient as set forth in claim 13, wherein the promoting of angiogenesis of the site upon application of said electromagnetic field and said platelet-rich plasma comprises: promoting the production of FGF-2 at the site upon the application of said electromagnetic field; and upregulating the proliferation of endothelial cells at the site upon application of said electromagnetic field. ### Claim 20 (depends on 13) The method for promoting angiogenesis at a site on a patient as set forth in claim 13, further comprising administering stem cells to the site, said stem selected from the group consisting of adipose stromal cells, stem cells derived from bone marrow aspirate, and combinations thereof. ### Claim 21 (depends on 20) The method for promoting angiogenesis at a site on a patient as set forth in claim 20, wherein the administering of stem cells to the site comprises: performing lipoaspiration on the patient to obtain adipose tissue, said adipose tissue including adipose stem cells and adipocytes; enzymatically digesting said adipose tissue; and separating said adipose stem cells from said adipocytes in said enzymatically digested adipose tissue. ### Claim 22 (depends on 20) The method for promoting angiogenesis at a site on a patient as set forth in claim 20, wherein the administering of stem cells to the site comprises: isolating bone marrow aspirate from the patient, said bone marrow aspirate including stem cells; centrifuging said bone marrow aspirate to concentrate said stem cells; isolating said concentrated stem cells derived from bone marrow aspirate. ### Claim 23 (depends on 13) The method for promoting angiogenesis at a site on a patient as set forth in claim 13, wherein the obtaining of blood compatible with the patient comprises identifying and obtaining donor blood compatible with the patient by matching blood cell surface antigens. ### Claim 24 (depends on 13) The method for promoting angiogenesis at a site on a patient as set forth in claim 13, wherein the administering of platelet-rich plasma to the site further comprises administering an isolated angiogenic factor selected from the group consisting of angiogenin, angiopoietin-1, del-1 protein, acidic fibroblast growth factor (aFGF or FGF-1), basic fibroblast growth factor (bFGF or FGF-2), follistatin, granulocyte colony-stimulating factor (G-CSF), hepatocyte growth factor (HGF), interleukin-8 (IL-8), leptin, midkine, placental growth factor, platelet-derived endothelial growth factor (PD-ECGF), platelet-derived growth factor (PDGF), pleiotrophin (PTN), progranulin, proliferin, transforming growth factor alpha (TGF-α), transforming growth factor beta (TGF-β), tumor necrosis factor alpha (TNF-α), vascular endothelial growth factor (VEGF), vascular permeability factor (VPF), and combinations thereof. ### Claim 25 (depends on 13) The method for promoting angiogenesis at a site on a patient as set forth in claim 13, wherein the site on the patient exhibits one of the following conditions: coronary artery disease, stroke, delayed wound healing, chronic wound, peripheral vascular disease, ischemia, chronic tendonosis, wound or tissue breakdown resulting from radiation treatment, and myocardial infarction. ### Claim 26 (depends on 13) The method for promoting angiogenesis as set forth in claim 13, wherein the isolating of the platelet-rich plasma comprises filtration. ### Claim 27 (depends on 26) The method for promoting angiogenesis at a site on a patient as set forth in claim 26, wherein the stimulating of the site with an electromagnetic field comprises: placing at least two electrodes across the site on the patient; and applying electrical energy to said electrodes so as to capacitively couple said electrodes and generate said electromagnetic field therebetween, said electromagnetic field passing through said platelet-rich plasma so as to promote angiogenesis at the site. ### Claim 28 (depends on 26) The method for promoting angiogenesis at a site on a patient as set forth in claim 26, wherein the stimulating of the site with an electromagnetic field comprises: placing a stimulation coil proximate to the site; and generating a pulsed electromagnetic field at the site by said stimulation coil, said pulsed electromagnetic field passing through said platelet-rich plasma so as to promote angiogenesis at the site. ### Claim 29 (depends on 26) The method for promoting angiogenesis at a site on a patient as set forth in claim 26, wherein the promoting of angiogenesis of the site upon application of said electromagnetic field and said platelet-rich plasma comprises: promoting the production of FGF-2 at the site upon the application of said electromagnetic field; and upregulating the proliferation of endothelial cells at the site upon application of said electromagnetic field. ### Claim 30 (depends on 26) The method for promoting angiogenesis at a site on a patient as set forth in claim 26, further comprising administering stem cells to the site, said stem selected from the group consisting of adipose stromal cells, stem cells derived from bone marrow aspirate, and combinations thereof. ### Claim 31 (depends on 26) The method for promoting angiogenesis at a site on a patient as set forth in claim 26, wherein the administering of platelet-rich plasma to the site further comprises administering an isolated angiogenic factor selected from the group consisting of angiogenin, angiopoietin-1, del-1 protein, acidic fibroblast growth factor (aFGF or FGF-1), basic fibroblast growth factor (bFGF or FGF-2), follistatin, granulocyte colony-stimulating factor (G-CSF), hepatocyte growth factor (HGF), interleukin-8 (IL-8), leptin, midkine, placental growth factor, platelet-derived endothelial growth factor (PD-ECGF), platelet-derived growth factor (PDGF), pleiotrophin (PTN), progranulin, proliferin, transforming growth factor alpha (TGF-α), transforming growth factor beta (TGF-β), tumor necrosis factor alpha (TNF-α), vascular endothelial growth factor (VEGF), vascular permeability factor (VPF), and combinations thereof.