# US 8,771,291 B2 · Dermal micro-organs, methods and apparatuses for producing 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 8,771,291 B2 - Document ID: US8771291B2 - Status: Granted - Kind: B2 - Application number: 13/686,939 - Filed: 2012-11-28 - Published: 2013-04-11 - Granted: 2014-07-08 - Earliest claimed: 2003-05-01 - Assignees: Medgenics Medical Israel Ltd. - Applicants: Medgenics Medical Israel Ltd. - Inventors: Stephen F. Bellomo; Alex Okun; Yaron Fuerst; David Shalhevet; Elisha Amir; Mordechay Bukhman - Web page: https://patentgrep.com/patent/US8771291B2 ## CPC - A61B 17/3468: {for implanting or removing devices, e.g. prostheses, implants, seeds, wires (devices for implanting seeds A61M37/0069)} - A61B 17/32053: {Punch like cutting instruments, e.g. using a cylindrical or oval knife (A61B17/326 takes precedence; trepans A61B17/1695)} - A61B 17/322: Skin grafting apparatus - A61F 2/105: {Skin implants, e.g. artificial skin} - A61K 35/36: Skin; Hair; Nails; Sebaceous glands; Cerumen; Epidermis; Epithelial cells; Keratinocytes; Langerhans cells; Ectodermal cells (islets of Langerhans A61K35/39) - A61K 38/193: {Colony stimulating factors [CSF]} - A61K 38/2066: {IL-10} - A61K 38/215: {IFN-beta} - A61K 38/27: Growth hormone [GH], i.e. somatotropin - A61K 38/28: Insulins - A61M 5/425: {Protruding skin to facilitate piercing, e.g. vacuum cylinders, vein immobilising means} - A61P 3/00: Drugs for disorders of the metabolism (of the blood or the extracellular fluid A61P7/00) - A61P 7/00: Drugs for disorders of the blood or the extracellular fluid - A61P 7/04: Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents - A61P 7/06: Antianaemics - A61P 17/00: Drugs for dermatological disorders - A61P 39/00: General protective or antinoxious agents - A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 - C12N 5/0698: {Skin equivalents} - A61B 10/0275: {with sample notch, e.g. on the side of inner stylet} - A61B 2017/0023: {disposable} - A61B 2017/00969: {used for transplantation} - A61B 2017/2808: {Clamp, e.g. towel clamp} - A61B 2017/320052: {Guides for cutting instruments} - A61B 2017/320064: {with tissue or sample retaining means} - A61B 2017/3225: {with processing of harvested tissue} - A61B 2217/005: with suction drainage system - A61K 38/1816: {Erythropoietin [EPO]} - C12N 2502/094: keratinocytes - C12N 2502/1323: Adult fibroblasts - C12N 2510/00: Genetically modified cells - Y10T 83/929: Tool or tool with support - A61B: DIAGNOSIS; SURGERY; IDENTIFICATION (usefulness limited to only animals A61D) - A61F: FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS (dental prosthetics A61C) - 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)} - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS - C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00) - Y10T: TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION ## Abstract Embodiments of the present invention provide Dermal Micro-organs (DMOs), methods and apparatuses for harvesting the same. Some embodiments of the invention provide a DMO including a plurality of dermal components, which substantially retain the micro-architecture and three dimensional structure of the dermal tissue from which they are derived. An apparatus for harvesting the DMO may include, according to some exemplary embodiments, a support configuration to support a skin-related tissue structure from which the DMO is to be harvested, and a cutting tool able to separate the DMO from the skin-related tissue structure. Exemplary embodiments of the invention provide a genetically modified dermal micro-organ expressing at least one recombinant gene product. Some embodiments of the invention provide methods and apparatuses for implanting a genetically modified DMO. ## Claims ### Claim 1 An apparatus for directly harvesting a dermal micro-organ from a subject comprising: (a) a support structure to support a skin-related tissue structure of a subject from which a dermal micro-organ is to be harvested, said support structure comprising; (i). a first tubular element comprising a site of insertion into the apparatus; (ii) a vacuum chamber comprising an inner support surface able to hold said skin-related tissue structure in a desired shape and position to enable a cutting tool to cut said dermal micro-organ directly from said skin-related tissue structure, wherein said first tubular element is connected to said vacuum chamber; and (iii) one or more vacuum channels to fluidically connect said vacuum chamber with at least one vacuum source; (b) an introducer; and (c) said cutting tool able to directly separate said dermal micro-organ from said skin-related tissue structure; wherein said dermal micro-organ is an explant of living tissue consisting essentially of a plurality of dermal components located below the epidermis and lacking a complete epidermal layer that substantially maintain the micro-architecture and three-dimensional structure of the dermal tissue from which they are obtained. ### Claim 2 (depends on 1) The apparatus of claim 1, wherein said vacuum chamber further comprises: (a) two elevated protrusions, a proximal elevated protrusion and a distal elevated protrusion relative to said site of insertion, said elevated protrusions able to support a plateau of epidermal and dermal skin layers from said skin-related tissue structure above the trajectory of said cutting tool; and (b) a central channel located between said two elevated protrusions, wherein said central channel supports said skin-related tissue structure under vacuum conditions, so that the dermal skin layer is within the trajectory of said cutting tool when said cutting tool is inserted in said first tubular element. ### Claim 3 (depends on 2) The apparatus of claim 2, wherein said first tubular element is configured to align said cutting tool coaxially into said central channel. ### Claim 4 (depends on 1) The apparatus of claim 1, wherein said introducer comprises a second tubular element and a fourth tubular element, wherein (a) said second tubular element inserts through said fourth tubular element and extends beyond the distal end of said fourth tubular element; (b) said second and fourth tubular elements together insert at said site of insertion coaxially within said first tubular element; and (c) said fourth tubular element remains coaxial and within said first tubular element upon withdrawal of said second tubular element. ### Claim 5 (depends on 4) The apparatus of claim 4, wherein said second tubular element comprises an inner needle and said fourth tubular element comprises an outer sleeve. ### Claim 6 (depends on 4) The apparatus of claim 4, wherein said cutting tool comprises a third tubular element able to be inserted at said site of insertion through said fourth tubular element that remains coaxial and within said first tubular element following the withdrawal of said second tubular element, wherein said cutting tool is substantially coaxially with said first tubular element, said third tubular element able to cut said dermal micro-organ from said skin-related tissue structure. ### Claim 7 (depends on 6) The apparatus of claim 6, wherein said third tubular element comprises a coring tube able to cut through said skin-related tissue structure when advance along a cutting axis, wherein said cutting axis is substantially coaxial with said first tubular element. ### Claim 8 (depends on 7) The apparatus of claim 7, wherein said coring tube comprises a rotatable coring tube attached to a power source. ### Claim 9 (depends on 8) The apparatus of claim 8, wherein said power source is selected from an electrical motor or an air driven turbine. ### Claim 10 (depends on 7) The apparatus of claim 7, wherein said coring tube is a coring needle with a symmetrically sharpened tip. ### Claim 11 (depends on 1) A method of directly harvesting a dermal micro-organ from a subject comprising the steps of: (a) positioning an apparatus of claim 1 at a harvest site in contact with an epidermal surface of said subject; (b) supporting a skin-related tissue structure of said subject at said harvest site from which a dermal micro-organ is to be harvested; (c) puncturing the skin-related tissue structure; (d) directly cutting said dermal micro-organ from said supported skin-related tissue structure; and (e) directly recovering said dermal micro-organ, wherein said dermal micro-organ is an explant of living tissue consisting essentially of a plurality of dermal components located below the epidermis and lacking a complete epidermal layer that substantially maintain the micro-architecture and three-dimensional structure of the dermal tissue from which they are obtained. ### Claim 12 (depends on 11) The method of claim 11, wherein said harvesting method comprises making only a single puncture point in said skin-related structure. ### Claim 13 (depends on 11) The method of claim 11, wherein said apparatus comprises: (a) a support structure to hold said skin-related tissue structure from which said dermal micro-organ is to be harvested, wherein said support structure comprises a first tubular element and a vacuum chamber, and wherein said first tubular element is a guide channel, which is substantially parallel with said epidermal surface of said subject, and wherein said guide channel is connected to said vacuum chamber; (b) an introducer comprising a second tubular element and a fourth tubular element, wherein said second tubular element comprises an inner needle and said fourth tubular element comprises outer sleeve, and said inner needle inserts through said outer sleeve and extends beyond the distal end of said outer sleeve; and (c) a cutting tool comprising a third tubular element able to be inserted into said outer sleeve positioned within and coaxially with said guide channel, wherein said third tubular element is a coring tube, which cuts said dermal micro-organ from said skin-related tissue structure. ### Claim 14 (depends on 13) The method of claim 13, wherein (a) said supporting comprises applying a vacuum condition to said vacuum chamber, wherein said vacuum condition causes said skin-related structure to be held at an inner support surface of said vacuum chamber; (b) said puncturing comprises inserting said introducer through said guide channel and into said skin-related structure followed by withdrawing said inner needle from said outer sleeve and from said skin-related structure, said outer sleeve remaining within said guide channel and within said skin-related structure; and (c) said cutting comprises inserting said coring tube through and coaxially within said outer sleeve, said coring tube entering said skin-related structure. ### Claim 15 (depends on 11) The method of claim 11, wherein said recovering comprises use of a vacuum to withdraw said dermal micro-organ from said coring tube into a closed container. ### Claim 16 (depends on 11) The method of claim 11, wherein said recovering comprises pushing said dermal micro-organ from said coring tube. ### Claim 17 (depends on 14) The method of claim 14, wherein said cutting further comprises the steps of: (a) rotating said coring tube, wherein said rotating coring tube is advanced towards the distal end of said apparatus; and (b) wherein said recovering further comprises withdrawing said coring tube from said skin-related structure while simultaneously applying a vacuum condition within said coring tube, said dermal micro-organ being withdrawn into a closed container.