# US 11,110,148 B2 · Silk fibroin materials and use thereof > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 11,110,148 B2 - Document ID: US11110148B2 - Status: Granted - Kind: B2 - Application number: 15/981,981 - Filed: 2018-05-17 - Published: 2019-01-10 - Granted: 2021-09-07 - Earliest claimed: 2003-01-07 - Assignees: Trustees of Tufts College; Massachusetts Institute of Technology - Applicants: Trustees of Tufts College; Massachusetts Institute of Technology - Inventors: David L. Kaplan; Rina Sears; Gordana Vunjak-Novakovic; Lorenz Meinel - Web page: https://patentgrep.com/patent/US11110148B2 ## CPC - A61K 38/1825: {Fibroblast growth factor [FGF]} - A61K 38/1841: {Transforming growth factor [TGF]} - A61K 47/42: Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein (oligopeptides having up to five amino acids {A61K47/183}; polyamino acids A61K47/34) - A61L 27/227: {Other specific proteins or polypeptides not covered by A61L27/222, A61L27/225 or A61L27/24} - A61L 27/26: Mixtures of macromolecular compounds - A61L 27/3604: {characterised by the human or animal origin of the biological material, e.g. hair, fascia, fish scales, silk, shellac, pericardium, pleura, renal tissue, amniotic membrane, parenchymal tissue, fetal tissue, muscle tissue, fat tissue, enamel} - A61L 27/3847: {Bones} - A61L 27/3852: {Cartilage, e.g. meniscus} - A61L 27/3895: {using specific culture conditions, e.g. stimulating differentiation of stem cells, pulsatile flow conditions} - A61L 27/56: Porous materials, {e.g. foams or sponges} - D01D 5/00: Formation of filaments, threads, or the like - D01F 4/02: from fibroin - A61L 2430/02: for reconstruction of bones; weight-bearing implants - Y10T 428/29: Coated or structually defined flake, particle, cell, strand, strand portion, rod, filament, macroscopic fiber or mass thereof - 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) - 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) - D01D: MECHANICAL METHODS OR APPARATUS IN THE MANUFACTURE OF ARTIFICIAL FILAMENTS, THREADS, FIBRES, BRISTLES OR RIBBONS - D01F: CHEMICAL FEATURES IN THE MANUFACTURE OF ARTIFICIAL FILAMENTS, THREADS, FIBRES, BRISTLES OR RIBBONS; APPARATUS SPECIALLY ADAPTED FOR THE MANUFACTURE OF CARBON FILAMENTS - Y10T: TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION ## Abstract The present invention provides processes for producing porous silk fibroin scaffold material. The porous silk fibroin scaffold can be used for tissue engineering. The porosity of the silk fibroin scaffolds described herein can be adjusted as to mimic the gradient of densities found in natural tissue. Accordingly, methods for engineering of 3-dimensional tissue, e.g. bone and cartilage, using the silk fibroin scaffold material are also provided. ## Claims ### Claim 1 A three-dimensional body comprising silk fibroin having interconnected pores, wherein the pores have an average diameter between 50 microns and 100 microns, and wherein total porosity of the three-dimensional body is at least 80%. ### Claim 2 (depends on 1) The three-dimensional body of claim 1, wherein the silk fibroin is in a beta-sheet conformation. ### Claim 3 (depends on 1) The three-dimensional body of claim 1, wherein the three-dimensional body comprises from 5% (w/v) to 35% (w/v) of the silk fibroin. ### Claim 4 (depends on 1) The three-dimensional body of claim 1, wherein the porosity is at least 90%. ### Claim 5 (depends on 1) The three-dimensional body of claim 1, wherein the porosity is at least 95%. ### Claim 6 (depends on 1) The three-dimensional body of claim 1, wherein the silk fibroin is substantially free of sericin. ### Claim 7 (depends on 1) The three-dimensional body of claim 1, wherein the three-dimensional body is an article for tissue engineering or tissue guided regeneration application. ### Claim 8 (depends on 1) The three-dimensional body of claim 1, wherein the three-dimensional body further comprises an additive. ### Claim 9 (depends on 7) The three-dimensional body of claim 7, wherein the additive is selected from peptides, antibodies, DNA, RNA, modified RNA/protein composites, glycogens or other sugars and alcohols. ### Claim 10 (depends on 7) The three-dimensional body of claim 7, wherein the additive is a biologically active or pharmaceutically active compound. ### Claim 11 (depends on 7) The three-dimensional body of claim 7, wherein the additive is an agent that enhances proliferation or differentiation of a cell. ### Claim 12 (depends on 7) The three-dimensional body of claim 7, wherein the additive is a bone morphogenetic protein, a basic fibroblast growth factor, an epidermal growth factor, a platelet-derived growth factor, an insulin-like growth factor or a transforming growth factor. ### Claim 13 (depends on 7) The three-dimensional body of claim 7, wherein the additive is selected from the group consisting of collagen, elastin, fibronectin, vitronectin, laminin and proteoglycans. ### Claim 14 (depends on 1) The three-dimensional body of claim 1, wherein the silk fibroin is selected from the group consisting of silks from silkworms, silks from spiders, silks from genetically engineered cells, silks from transgenic plants and animals, silks from cultured cells, native silk, silk from cloned full or partial sequences of native silk genes, and silk from synthetic genes encoding silk. ### Claim 15 (depends on 1) The three-dimensional body of claim 1, wherein the three-dimensional body comprises a cell. ### Claim 16 A three-dimensional silk fibroin body comprising interconnected pores having an average diameter between 50 microns and 100 microns, wherein the porosity is at least 80%, the silk fibroin body further comprising a biodegradable polymer selected from the group consisting of collagens, polylactic acid or its copolymers, polyglycolic acid or its copolymers, polyanhydrides, elastin, glycosaminoglycans, polysaccharides, and any combinations thereof.