# US 2014/0193477 A1 · Collagen based materials and uses related thereto > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2014/0193477 A1 - Document ID: US20140193477A1 - Status: Published application - Kind: A1 - Application number: 14/052,581 - Filed: 2013-10-11 - Published: 2014-07-10 - Earliest claimed: 2012-10-11 - Assignees: Emory University; Beth Israel Deaconess Medical Center, Inc. - Applicants: Emory University; Beth Israel Deaconess Medical Center, Inc. - Inventors: Elliot Chaikof; Jeffrey Caves; Vivek Ashok Kumar; Adam W. Martinez - Web page: https://patentgrep.com/patent/US20140193477A1 ## CPC - A61L 27/54: Biologically active materials, e.g. therapeutic substances {(A61L27/227 takes precedence)} - A61L 27/24: Collagen - A61L 27/34: Macromolecular materials - A61L 27/46: with phosphorus-containing inorganic fillers - A61L 27/507: {for artificial blood vessels (apparatus for applying cells on a blood vessel prosthesis A61F2/062)} - Y10T 428/249921: Web or sheet containing structurally defined element or component - 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) - Y10T: TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION ## Abstract This disclosure relates to materials fabricated from collagen and uses relates thereto. Typically, layers of collagen are stretched during a curing period and optionally coated or impregnated with an elastin like protein. In certain embodiments, these materials can be used in tissue repair or arranged into cylinders and utilized as a prosthetic vascular graft. ## Claims ### Claim 1 A synthetic material comprising fibril collagen matrix with a collagen density of greater than 600 micrograms per square centimeter and the collagen fibers maintain D-periodicity. ### Claim 2 (depends on 1) The material of claim 1, wherein the collagen fibers are separated on average by greater than 200 nanometers and less than 1 micrometer. ### Claim 3 (depends on 1) The material of claim 1, wherein the collagen matrix has a greater fibril alignment frequency in one direction. ### Claim 4 (depends on 1) The material of claim 1 is in the form of a sheet with a thickness of less than 50 micrometers. ### Claim 5 (depends on 4) The material of claim 4, wherein the sheet has a continuous surface area of greater than 2 square centimeters. ### Claim 6 (depends on 1) The material of claim 1, further comprising an elastic polymer comprising tetrapeptide, pentapeptide, or hexapeptide repeats comprising proline. ### Claim 7 (depends on 6) The material of claim 6, wherein the elastic polymer comprises peptide repeats of [YaaPUaaXaaZaap]n (SEQ ID NO:1) wherein Yaa is glycine, alanine, lucine, isolucine, or valine; P is Pro; Uaa is glycine, alanine, lucine, isolucine, or valine; Xaa is aspartic acid, glutamic acid, glycine, alanine, lucine, isolucine, or valine or any amino acid except Pro; Zaa is glycine, alanine, lucine, isolucine, or valine; p is 0, 1, 2, 3, 4, 5, or 6; and n is 1 to 1000. ### Claim 8 (depends on 7) The material of claim 7 wherein the elastic polymer comprises a protein copolymer comprising at least one hydrophilic block and at least one hydrophobic block, said copolymer having a first hydrophobic end block, a second hydrophobic end block, and a middle hydrophilic block. ### Claim 9 (depends on 8) The material of claim 8 wherein said middle block comprises [YaaPUaaXaaZaap]n (SEQ ID NO:1) wherein Yaa is glycine, alanine, lucine, isolucine, or valine; P is Pro; Uaa is glycine, alanine, lucine, isolucine, or valine; Xaa is, the same or different at each occurrence; aspartic acid, glutamic acid, glycine, alanine, lucine, isolucine, or valine or any amino acid except Pro; Zaa is glycine, alanine, lucine, isolucine, or valine; p is 0, 1, 2, 3, 4, 5, or 6; and n is 1 to 1000. ### Claim 10 (depends on 8) The material of claim 8 wherein said first and second end blocks comprise [YaaPUaaXaaZaap]n (SEQ ID NO:1) wherein Yaa is glycine, alanine, lucine, isolucine, or valine; P is Pro; Uaa is glycine, alanine, lucine, isolucine, or valine; Xaa is, the same or different at each occurrence; glycine, alanine, lucine, isolucine, or valine; Zaa is glycine, alanine, lucine, isolucine, or valine; p is 0, 1, 2, 3, 4, 5, or 6; and n is 1 to 1000. ### Claim 11 (depends on 8) The material of claim 8, wherein the middle block comprises [(VPGAG)pVPGXaaG(VPGAG)q]n (SEQ ID NO:2) wherein Xaa is glutamic acid or aspartic acid, arginine, histidine, lysine, serine, threonine, asparagine, or glutamine; p is 0, 1, 2, or 3; q is 0, 1, 2, or 3; n is 1 to 1000, or n is between 10-100. ### Claim 12 (depends on 8) The material of claim 8, wherein said first and second end blocks comprise [IPAVG]n (SEQ ID NO:3) wherein n is 1 to 200 or 5 to 200. ### Claim 13 (depends on 8) The material of claim 8, wherein the copolymer comprises a peptide sequence comprising lysine between the middle block and the first or second blocks. ### Claim 14 (depends on 6) The material of claim 6, wherein the elastic polymer is within the collagen matrix. ### Claim 15 A method of making a sheet of collagen comprising a) mixing an acid solution comprising acid soluble collagen with a buffer under conditions such that a collagen gel forms; b) incubating the collagen gel in an aqueous buffer solution at a neutral pH for more than one day providing a cured layer of collagen; c) separating the cured layer of collagen from the buffer solution; and d) drying the cured layer of collagen to provide dried collagen. ### Claim 16 (depends on 15) The method of claim 15, wherein the collagen gel is stretched to greater than 1, 5, 10 or 20% of the original length in one direction providing a stretched layer of collagen. ### Claim 17 (depends on 15) The method of claim 15, wherein the collagen gel is stretched in the buffer solution. ### Claim 18 (depends on 15) The method of claim 15, wherein the collagen gel is stretched at a speed of less than 200, 100, 50, 10, or 5 micrometers per second. ### Claim 19 (depends on 16) The method of claim 16, wherein the stretched layer of collagen is dried providing a stretched dried layer of collagen. ### Claim 20 (depends on 19) The method of claim 19, further comprising the step of applying a layer of collagen gel to the stretched dried layer of collagen and drying the collagen gel under conditions such that a coated stretched dried layer of collagen forms. ### Claim 21 (depends on 19) The method of claim 19, further comprising the steps of hydrating the stretched dried layer of collagen providing a hydrated stretched layer of collagen, applying a layer of collagen gel to the hydrated stretched layer of collagen and drying the hydrated stretched collagen gel under conditions such that a coated stretched dried layer of collagen forms. ### Claim 22 (depends on 19) The method of claim 19, wherein hydrating the stretched dried layer of collagen is performed on a cylindrical surface wherein the first stretched direction is parallel to the axis of the cylindrical surface. ### Claim 23 A method of producing a material comprising a layer of collagen and a layer of elastic polymer comprising a) cooling an acid solution to less than 15 degrees Celsius providing a cooled solution comprising, acid soluble collagen, and a protein comprising peptide repeats of [YaaPUaaXaaZaap]n (SEQ ID NO:1) wherein Yaa is glycine, alanine, lucine, isolucine, or valine; P is Pro; Uaa is glycine, alanine, lucine, isolucine, or valine; Xaa is aspartic acid, glutamic acid, glycine, alanine, lucine, isolucine, or valine or any amino acid except Pro; Zaa is glycine, alanine, lucine, isolucine, or valine; p is 0, 1, 2, 3, 4, 5, or 6; and n is 1 to 1000; b) neutralizing the cooled solution such that a collagen layer forms; and c) warming the solution under conditions such that an elastic layer forms. ### Claim 24 (canceled) ### Claim 25 A method of producing a material comprising a) contacting a dried collagen sheet with a solution cooled to less than 15 degree Celsius wherein the cooled solution comprises a protein comprising peptide repeats of [YaaPUaaXaaZaap]n (SEQ ID NO:1) wherein Yaa is glycine, alanine, lucine, isolucine, or valine; P is Pro; Uaa is glycine, alanine, lucine, isolucine, or valine; Xaa is aspartic acid, glutamic acid, glycine, alanine, lucine, isolucine, or valine or any amino acid except Pro; Zaa is glycine, alanine, lucine, isolucine, or valine; p is 0, 1, 2, 3, 4, 5, or 6; and n is 1 to 1000; and b) warming the solution under conditions such that an elastic polymer layer forms over the dried collagen sheet. ### Claim 26 (depends on 15) A material made by the process of claim 15. ### Claim 27 (depends on 1) An artificial vascular prosthesis comprising a material as in claim 1. ### Claim 28 (depends on 1) A method of producing a pattern comprising cutting a material as in claim 1. ### Claim at position 29 29-30. (canceled) ### Claim 31 (depends on 1) A material as in claim 1, further comprising a cell. ### Claim 32 (canceled) ### Claim 33 (depends on 1) A material as in claim 1, further comprising a therapeutic agent. ### Claim 34 (canceled) ### Claim 35 (depends on 1) A material as in claim 1, further comprising bone granules or minerals, calcium phosphates, hydroxyapatite, tricalcium phosphate, or calcium sulphate.