# US 8,772,456 B2 · Fibrous protein fusion and use thereof in the formation of advanced organic/inorganic composite materials > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 8,772,456 B2 - Document ID: US8772456B2 - Status: Granted - Kind: B2 - Application number: 13/934,828 - Filed: 2013-07-03 - Published: 2014-05-22 - Granted: 2014-07-08 - Earliest claimed: 2005-01-14 - Assignees: Trustees of Tufts College - Applicants: Trustees of Tufts College; University of Illinois at Chicago - Inventors: David L. Kaplan; Jia Huang; Cheryl Wong Po Foo; Rajesh Naik; Anne George - Web page: https://patentgrep.com/patent/US8772456B2 ## CPC - A61L 27/48: with macromolecular fillers - A61L 27/446: {with other specific inorganic fillers other than those covered by A61L27/443 or A61L27/46} - A61L 27/46: with phosphorus-containing inorganic fillers - A61L 27/54: Biologically active materials, e.g. therapeutic substances {(A61L27/227 takes precedence)} - C07K 14/43518: {from spiders} - C07K 14/51: Bone morphogenetic factor; Osteogenins; Osteogenic factor; Bone-inducing factor - C07K 14/78: Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin or cold insoluble globulin [CIG] - A61L 2430/00: Materials or treatment for tissue regeneration - C07K 2319/00: Fusion polypeptide - 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) - C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00) ## Abstract The claimed invention provides a fusion polypeptide comprising a fibrous protein domain and a mineralization domain. The fusion is used to form an organic-inorganic composite. These organic-inorganic composites can be constructed from the nano- to the macro-scale depending on the size of the fibrous protein fusion domain used. In one embodiment, the composites can also be loaded with other compounds (e.g., dyes, drugs, enzymes) depending on the goal for the materials, to further enhance function. This can be achieved during assembly of the material or during the mineralization step in materials formation. ## Claims ### Claim 1 An organic-inorganic composite material comprising: (i) a fusion polypeptide comprising a fibrous protein domain comprising the amino acid sequence as set forth in SEQ ID NO: 1 or 3 and a mineralizing domain, wherein the mineralizing domain is capable of inducing mineralization, and is obtained from dentin matrix protein 1 (DMP1), bone sialoprotein (BSP), silaffin-1 (Sil1) protein, or functional fragments thereof; and (ii) an inorganic material. ### Claim 2 (depends on 1) The organic-inorganic composite material of claim 1, wherein the fibrous protein domain is obtained from silk, collagens, coiled-coiled leucine zipper proteins, elastins, keratins, actins, or tubulins. ### Claim 3 (depends on 1) The organic-inorganic composite material of claim 1, wherein the fibrous protein domain comprises an amino acid sequence from the silk protein Spidroin 1. ### Claim 4 (depends on 1) The organic-inorganic composite material of claim 1, wherein the fibrous protein domain comprises an amino acid sequence as set forth in SEQ ID NO: 4 or SEQ ID NO: 5. ### Claim 5 (depends on 1) The organic-inorganic composite material of claim 1, wherein the fusion polypeptide is crystallized. ### Claim 6 (depends on 1) The organic-inorganic composite material of claim 1, wherein the mineralizing domain induces the formation of hydroxyapatite, silica, cadmium sulfide or magnetite. ### Claim 7 (depends on 1) The organic-inorganic composite material of claim 1, wherein the mineralization domain comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 6, 8, and 17-21. ### Claim 8 (depends on 7) The organic-inorganic composite material of claim 7, wherein the mineralization domain comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 7, 22, and 23. ### Claim 9 (depends on 1) The organic-inorganic composite material of claim 1, wherein the fusion polypeptide comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 9-12, 24, and 25. ### Claim 10 (depends on 1) The organic-inorganic composite material of claim 1, wherein the inorganic material is hydroxyapatite or silica. ### Claim 11 (depends on 1) The organic-inorganic composite material of claim 1, wherein the organic-inorganic composite material further comprises an active agent. ### Claim 12 (depends on 11) The organic-inorganic composite material of claim 11, wherein the agent is selected from the group consisting of naturally derived or genetically engineered proteins, polysaccharides, glycoproteins, lipoproteins, peptides, nucleic acids, PNAs, aptamers, antibodies, small molecules, and cells. ### Claim 13 (depends on 11) The organic-inorganic composite material of claim 11, wherein the agent is a therapeutic agent, a cell attachment mediator, a hormone, a chemoattractant, or a growth factor. ### Claim 14 (depends on 13) The organic-inorganic composite material of claim 13, wherein the cell attachment mediator comprises an integrin binding amino acid sequence. ### Claim 15 (depends on 13) The organic-inorganic composite material of claim 13, wherein the therapeutic agent is selected from the group consisting of anti-infectives; chemotherapeutic agents; anti-rejection agents; analgesics and analgesic combinations; and anti-inflammatory agents. ### Claim 16 (depends on 13) The organic-inorganic composite material of claim 13, wherein the growth factor is selected from the group consisting of bone morphogenic proteins, bone morphogenaic-like proteins, epidermal growth factors, fibroblast growth factors, platelet derived growth factor (PDGF), insulin like growth factors, transforming growth factors, and vascular endothelial growth factor (VEGF). ### Claim 17 (depends on 1) The organic-inorganic composite material of claim 1, wherein the organic-inorganic composite material is in a form selected from a fiber, a film, a sponge, a gel, a foam, and a micropatterned foam. ### Claim 18 (depends on 1) A tissue engineered scaffold comprising an organic-inorganic composite material of claim 1.