# US 2013/0157360 A1 · Biomimetic tissue scaffold and methods of making and using same > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2013/0157360 A1 - Document ID: US20130157360A1 - Status: Published application - Kind: A1 - Application number: 13/806,225 - Filed: 2011-06-24 - Published: 2013-06-20 - Earliest claimed: 2010-06-25 - Assignees: Cornell University - Inventors: John C. March; Jiajie Yu; Jong Hwan Sung - Web page: https://patentgrep.com/patent/US20130157360A1 ## CPC - A61L 27/14: Macromolecular materials - B29C 33/3857: {by making impressions of one or more parts of models, e.g. shaped articles and including possible subsequent assembly of the parts} - B29C 33/424: {Moulding surfaces provided with means for marking or patterning (for injection moulding B29C45/372)} - B29K 2083/00: Use of polymers having silicon, with or without sulfur, nitrogen, oxygen, or carbon only, in the main chain, as moulding material - 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) - B29C: SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING (making preforms B29B11/00; making laminated products by combining previously unconnected layers which become one product whose layers will remain together B32B37/00 - B32B41/00) - B29K: INDEXING SCHEME ASSOCIATED WITH SUBCLASSES B29B, B29C OR B29D, RELATING TO MOULDING MATERIALS OR TO MATERIALS FOR {MOULDS, } REINFORCEMENTS, FILLERS OR PREFORMED PARTS, e.g. INSERTS ## Abstract Three-dimensional biomimetic tissue scaffolds, as well as methods of manufacture of these scaffolds. The method is fully customizable to create a biomimetic tissue scaffold with shapes, densities, and geometries similar or identical to the tissue it imitates. For example, physiologically realistic collagen/PEG villi created using the method are designed to have a high-aspect ratio and curvature similar to villi found in the human small intestine. Accordingly, the biomimetic tissue scaffolds serve as an improved in vitro model for a wide variety of physiological research, as well as pharmacological testing and drug, compound, and/or metabolite uptake by cells growing on the scaffold, among many other uses. ## Claims ### Claim 1 A method for making a three-dimensional biomimetic scaffold capable of supporting growth of a cell, the method comprising the steps of: forming a first three-dimensional shape in a first mold; filling at least a portion of the three-dimensional shape in the first mold with a first polymerizable compound; causing said first polymerizable compound to polymerize to form a three-dimensional scaffold, wherein said three-dimensional scaffold is complementary to said three-dimensional shape; and removing said three-dimensional scaffold from said first mold. ### Claim 2 (depends on 1) The method of claim 1, wherein said first mold comprises a plastic. ### Claim 3 (depends on 1) The method of claim 1, wherein said three-dimensional shape is formed using laser ablation. ### Claim 4 (depends on 1) The method of claim 1, wherein said first mold comprises a plurality of three-dimensional indentations. ### Claim 5 (depends on 4) The method of claim 4, wherein each of said plurality of indentations has a maximum height and a maximum width, and further wherein for a majority of said plurality of indentations the maximum height of said indentation is greater than the maximum width of said indentation. ### Claim 6 (depends on 5) The method of claim 5, wherein a majority of said plurality of indentations have a conical shape. ### Claim 7 (depends on 1) The method of claim 1, wherein said first polymerizable compound comprises a silicone. ### Claim 8 (depends on 7) The method of claim 7, wherein said first polymerizable compound comprises polydimethylsiloxane. ### Claim 9 (depends on 1) The method of claim 1, further comprising the step of seeding said first polymerizable compound with a cell at some point prior to the step of causing said first polymerizable compound to polymerize to form a three-dimensional scaffold. ### Claim 11 A method for making a three-dimensional biomimetic scaffold capable of supporting growth of a cell, the method comprising the steps of: filling at least a portion of a three-dimensional shape formed in a first mold with a first polymerizable compound; causing said first polymerizable compound to polymerize to form a second mold, wherein at least a portion of said second mold comprises a first structure, said first structure being complementary to said three-dimensional shape; removing said second mold from said first mold; using said second mold to form a third mold from a second polymerizable compound; removing said third mold from said second mold; and using said third mold to form a three-dimensional scaffold from a third polymerizable compound, wherein said three-dimensional scaffold is complementary to said three-dimensional shape. ### Claim 12 (depends on 11) The method of claim 11, further comprising the step of: removing the third mold away from the three-dimensional scaffold. ### Claim 13 (depends on 11) The method of claim 11, wherein said first mold comprises a plastic. ### Claim 14 (depends on 11) The method of claim 11, wherein said first mold comprises poly (methyl methacrylate). ### Claim 15 (depends on 11) The method of claim 11, further comprising the step of: forming the first three-dimensional shape in the first mold. ### Claim 16 (depends on 15) The method of claim 15, wherein said three-dimensional shape is formed using laser ablation. ### Claim 17 (depends on 11) The method of claim 11, wherein said first mold comprises a plurality of three-dimensional indentations. ### Claim 18 (depends on 17) The method of claim 17, wherein each of said plurality of indentations has a maximum height and a maximum width, and further wherein for a majority of said plurality of indentations the maximum height of said indentation is greater than the maximum width of said indentation. ### Claim 19 (depends on 18) The method of claim 18, wherein a majority of said plurality of indentations have a conical shape. ### Claim 20 (depends on 11) The method of claim 11, wherein said first polymerizable compound comprises a silicone. ### Claim 21 (depends on 20) The method of claim 20, wherein said first polymerizable compound comprises polydimethylsiloxane. ### Claim 22 (depends on 11) The method of claim 11, wherein said second polymerizable compound comprises alginate. ### Claim 23 (depends on 11) The method of claim 11, wherein the step of removing the third mold away from the three-dimensional scaffold comprises addition of a chelator. ### Claim 24 (depends on 23) The method of claim 23, wherein said chelator is ethylenediaminetetraacetic acid. ### Claim 25 (depends on 11) The method of claim 11, wherein said second polymerizable compound is selected from the group consisting of a hydrogel, alginate, gelatin, chitosan, collagen, poly-N-isopropylacrylamide, a polysaccharide-based polymer, poly(ethylene glycol), poly(ethylene glycol)diacrylate, and combinations thereof. ### Claim 26 (depends on 11) The method of claim 11, wherein said third polymerizable compound comprises a hydrogel. ### Claim 27 (depends on 26) The method of claim 26, wherein said hydrogel is selected from the group consisting of gelatin, chitosan, collagen, poly-N-isopropylacrylamide, a polysaccharide-based polymer, poly(ethylene glycol), poly(ethylene glycol)diacrylate, laminin, fibronectin, entactin, and combinations thereof. ### Claim 28 (depends on 11) The method of claim 11, wherein said third polymerizable compound further comprises a basement membrane protein. ### Claim 29 (depends on 11) The method of claim 11, further comprising the step of seeding said third polymerizable compound with a cell at some point prior to the step of using said third mold to form said three-dimensional hydrogel scaffold. ### Claim 30 (depends on 11) The method of claim 11, further comprising the steps of seeding the three-dimensional scaffold with a cell; and incubating the cell. ### Claim 31 (depends on 11) The method of claim 11, further comprising the step of: using said three-dimensional scaffold for pharmacological testing. ### Claim 32 (depends on 11) The method of claim 11, further comprising the step of: using said three-dimensional scaffold to examine a biological process. ### Claim 33 (depends on 11) The method of claim 11, further comprising the step of: using said three-dimensional scaffold for toxicological testing. ### Claim 34 A system for making a three-dimensional biomimetic scaffold capable of supporting growth of a cell, the system comprising: a first mold comprising a three-dimensional shape; a second mold formed from said first mold using a first polymerizable compound; and a third mold formed from said second mold using a second polymerizable compound, wherein said third mold is configured to form a three-dimensional scaffold complementary to said three-dimensional shape. ### Claim 35 (depends on 34) The system of claim 34, wherein the polymerization of said second polymerizable compound is reversible. ### Claim 36 (depends on 34) The system of claim 34, wherein said first mold comprises a plurality of three-dimensional indentations. ### Claim 37 (depends on 36) The system of claim 36, wherein each of said plurality of indentations has a maximum height and a maximum width, and further wherein for a majority of said plurality of indentations the maximum height of said indentation is greater than the maximum width of said indentation. ### Claim 38 (depends on 34) The system of claim 34, wherein said second polymerizable compound is selected from the group consisting of a hydrogel, alginate, gelatin, chitosan, collagen, poly-N-isopropylacrylamide, a polysaccharide-based polymer, poly(ethylene glycol), poly(ethylene glycol)diacrylate, and combinations thereof. ### Claim 39 (depends on 34) The system of claim 34, wherein said third polymerizable compound comprises a hydrogel. ### Claim 40 (depends on 39) The system of claim 39, wherein said hydrogel is selected from the group consisting of gelatin, chitosan, collagen, poly-N-isopropylacrylamide, a polysaccharide-based polymer, poly(ethylene glycol), poly(ethylene glycol)diacrylate, laminin, fibronectin, entactin, and combinations thereof. ### Claim 41 (depends on 34) The system of claim 34, wherein said third polymerizable compound further comprises a basement membrane protein. ### Claim 42 (depends on 34) The system of claim 34, further comprising: a cell seeded on or in said three-dimensional scaffold. ### Claim 43 (depends on 1) A three-dimensional scaffold formed by the method of claim 1. ### Claim 44 (depends on 43) The three-dimensional scaffold of claim 43, wherein said scaffold comprises a polymerized hydrogel. ### Claim 45 (depends on 43) The three-dimensional scaffold of claim 43, further comprising: a cell seeded on or in said scaffold. ### Claim 46 (depends on 43) The three-dimensional scaffold of claim 43, wherein said scaffold comprises a plurality of three-dimensional shapes. ### Claim 47 (depends on 46) The three-dimensional scaffold of claim 46, wherein each of said plurality of three-dimensional shapes comprises a high-aspect ratio of height to width. ### Claim 48 A method for making an intestinal reactor, the method comprising the steps of: forming a biomimetic scaffold comprising a plurality of villi; seeding at least one of said villi with a cell; and forming a hollow tube from said seeded biomimetic scaffold, said hollow tube having an interior surface and an exterior surface. ### Claim 49 (depends on 48) The method of claim 48, wherein said villi are located on the interior surface of said hollow tube. ### Claim 50 (depends on 48) The method of claim 48, wherein said villi are located on the exterior surface of said hollow tube. ### Claim 51 (depends on 48) The method of claim 48, further comprising the step of: adding a microorganism to said intestinal reactor. ### Claim 52 (depends on 48) The method of claim 48, further comprising the step of: adding nutrients to said intestinal reactor. ### Claim 53 (depends on 48) The method of claim 48, further comprising the step of: using said intestinal reactor for pharmacological testing. ### Claim 54 (depends on 48) The method of claim 48, further comprising the step of: using said intestinal reactor to examine an intestinal process. ### Claim 55 (depends on 48) An intestinal reactor formed by the method of claim 48.