# US 2018/0008747 A1 · Bone tissue engineering by ex vivo stem cells ongrowth into three-dimensional trabecular metal > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2018/0008747 A1 - Document ID: US20180008747A1 - Status: Published application - Kind: A1 - Application number: 15/710,398 - Filed: 2017-09-20 - Published: 2018-01-11 - Earliest claimed: 2004-01-27 - Assignees: Zimmer Trabecular Metal Technology, Inc. - Applicants: Zimmer Trabecular Metal Technology, Inc. - Inventors: Zou Xuenong; Haisheng Li; Cody Bunger - Web page: https://patentgrep.com/patent/US20180008747A1 ## CPC - A61L 27/56: Porous materials, {e.g. foams or sponges} - A61F 2/28: Bones - A61F 2/34: Acetabular cups - A61L 27/00: Materials for {grafts or} prostheses or for coating {grafts or} prostheses (dental prostheses A61C13/00; shape or structure of prostheses A61F2/00; use of preparations for artificial teeth A61K6/80; artificial kidneys A61M1/14) - A61L 27/20: Polysaccharides - A61L 27/22: Polypeptides or derivatives thereof {, e.g. degradation products} - A61L 27/3608: {Bone, e.g. demineralised bone matrix [DBM], bone powder} - A61L 27/365: {Bones} - A61L 27/38: {containing added animal cells (organs or tissue containing native cells A61L27/36)} - A61L 27/54: Biologically active materials, e.g. therapeutic substances {(A61L27/227 takes precedence)} - C12N 5/0068: {General culture methods using substrates (for specific animal cell type C12N5/06)} - C12N 5/0662: {Stem cells} - A61F 2/30767: {Special external or bone-contacting surface, e.g. coating for improving bone ingrowth} - A61F 2/3094: {Designing or manufacturing processes} - A61F 2/32: for the hip - A61F 2/36: Femoral heads {; Femoral endoprostheses} - A61F 2/38: for elbows or knees - A61F 2/44: for the spine, e.g. vertebrae or spinal discs - A61F 2/4644: {Preparation of bone graft, bone plugs or bone dowels, e.g. grinding or milling bone material (bone material A61F2/28; disintegrating or milling devices B02C)} - A61F 2002/0086: {for preferentially controlling or promoting the growth of specific types of cells or tissues} - A61F 2002/2817: {Bone stimulation by chemical reactions or by osteogenic or biological products for enhancing ossification, e.g. by bone morphogenetic or morphogenic proteins [BMP] or by transforming growth factors [TGF]} - A61F 2002/2835: {Bone graft implants for filling a bony defect or an endoprosthesis cavity, e.g. by synthetic material or biological material} - A61F 2002/30199: {Three-dimensional shapes} - A61F 2002/30225: {Flat cylinders, i.e. discs} - A61F 2002/30677: {Means for introducing or releasing pharmaceutical products, e.g. antibiotics, into the body} - A61F 2002/3093: {for promoting ingrowth of bone tissue} - A61F 2002/4648: {Means for culturing bone graft} - A61F 2230/0063: Three-dimensional shapes - A61F 2230/0069: cylindrical - A61F 2310/00161: Carbon; Graphite - A61F 2310/00293: containing a phosphorus-containing compound, e.g. apatite - A61F 2310/00341: Coral, e.g. aragonite, porite - A61F 2310/00491: Coating made of niobium or Nb-based alloys - A61F 2310/00544: Coating made of tantalum or Ta-based alloys - A61F 2310/00976: Coating or prosthesis-covering structure made of proteins or of polypeptides, e.g. of bone morphogenic proteins BMP or of transforming growth factors TGF - A61F 2310/00982: Coating made of collagen - A61L 2300/222: Steroids, e.g. corticosteroids - A61L 2300/252: Polypeptides, proteins, e.g. glycoproteins, lipoproteins, cytokines - A61L 2300/606: Coatings - A61L 2300/64: Animal cells - A61L 2400/18: Modification of implant surfaces in order to improve biocompatibility, cell growth, fixation of biomolecules, e.g. plasma treatment - A61L 2430/00: Materials or treatment for tissue regeneration - 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) - 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) - C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00) ## Abstract Adult autologous stem cells cultured on a porous, three-dimensional tissue scaffold-implant for bone regeneration by the use of a hyaluronan and/or dexamethasone to accelerate bone healing alone or in combination with recombinant growth factors or transfected osteogenic genes. The scaffold-implant may be machined into a custom-shaped three-dimensional cell culture system for support of cell growth, reservoir for peptides, recombinant growth factors, cytokines and antineoplastic drugs in the presence of a hyaluronan and/or dexamethasone alone or in combination with growth factors or transfected osteogenic genes, to be assembled ex vivo in a tissue incubator for implantation into bone tissue. ## Claims ### Claim 1 (canceled) ### Claim 2 A method of generating tissue, comprising: providing or obtaining a tissue scaffold implant comprising a shaped, porous three-dimensional tissue scaffold with an inert biocompatible metal film present on surfaces of the porous three-dimensional tissue scaffold and with living cells in pores of the porous three-dimensional tissue scaffold, said porous three-dimensional tissue scaffold having an interconnected porosity for facilitating nutrient diffusion and media circulation throughout the porous three-dimensional tissue scaffold; and placing said tissue scaffold implant in an ex-vivo bioreactor for generating tissue on said porous three-dimensional tissue scaffold. ### Claim 3 (depends on 2) The method of claim 2, wherein said tissue scaffold implant is shaped and sized as an acetabular cup implant. ### Claim 4 (depends on 2) The method of claim 2, wherein said porous three-dimensional tissue scaffold has a porosity of 50% to 90%. ### Claim 5 (depends on 2) The method of claim 2, wherein said inert biocompatible metal film is a chemical vapor deposited metal film. ### Claim 6 (depends on 2) The method of claim 2, wherein said living cells comprise mesenchymal stem cells. ### Claim 7 (depends on 2) The method of claim 2 further comprising at least one substance on surfaces of the inert biocompatible metal film that is present on surfaces of the porous three-dimensional tissue scaffold with said living cells on said at least one substance, said at least one substance selected from the group consisting of a hyaluronan, dexamethasone, protein, peptide, transcript factor, cytokine, therapeutic agent, chitosan, polymer, osteogenic gene and growth factor. ### Claim 8 (depends on 2) The method of claim 2, wherein said porous three-dimensional tissue scaffold is a porous three-dimensional metallic tissue scaffold. ### Claim 9 (depends on 2) The method of claim 2 further comprising at least one substance having been applied ex-vivo with said living cells, said at least one substance selected from the group consisting of a hyaluronan, dexamethasone, protein, peptide, transcript factor, cytokine, therapeutic agent, chitosan, polymer, osteogenic gene and growth factor. ### Claim 10 A tissue scaffold implant for implantation in a patient, comprising: a shaped, porous three-dimensional tissue scaffold that is effective to receive tissue ingrowth upon implantation in a patient; an inert biocompatible metal film present on surfaces of the porous three-dimensional tissue scaffold; and ex-vivo applied, living cells in pores of the porous three-dimensional tissue scaffold. ### Claim 11 (depends on 10) The tissue scaffold implant of claim 10 shaped and sized as an acetabular cup implant. ### Claim 12 (depends on 10) The tissue scaffold implant of claim 10, wherein said inert biocompatible metal film is a chemical vapor deposited metal film. ### Claim 13 (depends on 10) The tissue scaffold implant of claim 10, wherein said living cells comprise mesenchymal stem cells. ### Claim 14 (depends on 10) The tissue scaffold implant of claim 10, wherein said porous three-dimensional tissue scaffold has a porosity of 50% to 90%. ### Claim 15 (depends on 10) The tissue scaffold implant of claim 10 further comprising at least one substance on surfaces of the inert biocompatible metal film that is present on surfaces of the porous three-dimensional tissue scaffold with said living cells on said at least one substance, said at least one substance selected from the group consisting of a hyaluronan, dexamethasone, protein, peptide, transcript factor, cytokine, therapeutic agent, chitosan, polymer, osteogenic gene and growth factor. ### Claim 16 (depends on 10) The tissue scaffold implant of claim 10, wherein said porous three-dimensional tissue scaffold is a porous three-dimensional metallic tissue scaffold. ### Claim 17 (depends on 10) The tissue scaffold implant of claim 10 further comprising at least one substance having been applied ex-vivo with said living cells, said at least one substance selected from the group consisting of a hyaluronan, dexamethasone, protein, peptide, transcript factor, cytokine, therapeutic agent, chitosan, polymer, osteogenic gene and growth factor. ### Claim 18 A tissue scaffold implant for implantation in a patient, comprising: a shaped, porous three-dimensional tissue scaffold fabricated as a single implant piece and effective to receive tissue ingrowth upon implantation in a patient, said porous three-dimensional tissue scaffold having an interconnected porosity for facilitating nutrient diffusion and media circulation throughout the porous three-dimensional tissue scaffold; and ex-vivo cultured tissue on the porous three-dimensional tissue scaffold. ### Claim 19 (depends on 18) The tissue scaffold implant of claim 18 further comprising an inert biocompatible metal film present on surfaces of the porous three-dimensional tissue scaffold. ### Claim 20 (depends on 19) The tissue scaffold implant of claim 19, wherein said inert biocompatible metal film is a chemical vapor deposited metal film. ### Claim 21 (depends on 18) The tissue scaffold implant of claim 18, wherein the tissue scaffold implant is shaped and sized as an acetabular cup implant. ### Claim 22 A method of implantation, comprising: providing or obtaining a tissue scaffold implant that is effective to receive tissue ingrowth upon implantation in a patient, said tissue scaffold implant comprising a shaped, porous three-dimensional tissue scaffold with ex-vivo cultured tissue on the porous three-dimensional tissue scaffold; and implanting said tissue scaffold implant in a patient. ### Claim 23 (depends on 22) The method of claim 22, wherein tissue scaffold implant further comprises an inert biocompatible metal film present on surfaces of the porous three-dimensional tissue scaffold. ### Claim 24 (depends on 23) The method of claim 23, wherein said inert biocompatible metal film is a chemical vapor deposited metal film.