# US 10,119,202 B2 · Method for preparing electro-mechanically stretched hydrogel micro fibers > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,119,202 B2 - Document ID: US10119202B2 - Status: Granted - Kind: B2 - Application number: 14/398,072 - Filed: 2013-04-30 - Published: 2015-04-30 - Granted: 2018-11-06 - Earliest claimed: 2012-04-30 - Assignees: The Johns Hopkins University - Applicants: The Johns Hopkins University - Inventors: Hai-Quan Mao; Shuming Zhang; Xi Liu; Brian Patrick Ginn - Web page: https://patentgrep.com/patent/US10119202B2 ## CPC - D01D 5/003: {the material being a polymer solution or dispersion (D01D5/0053 takes precedence)} - A61L 27/48: with macromolecular fillers - A61L 27/52: Hydrogels or hydrocolloids - A61L 27/54: Biologically active materials, e.g. therapeutic substances {(A61L27/227 takes precedence)} - D01D 5/0046: {the fibre formed by coagulation, i.e. wet electro-spinning} - D01D 5/0076: {characterised by the collecting device, e.g. drum, wheel, endless belt, plate or grid (D01D5/0046 takes precedence)} - D01D 5/06: Wet spinning methods {(D01D5/0046 takes precedence)} - D01D 5/12: Stretch-spinning methods ({D01D5/098 takes precedence} finishing by stretching D02J1/22) - D01F 2/00: Monocomponent artificial filaments or the like of cellulose or cellulose derivatives; Manufacture thereof - D06M 10/001: {Treatment with visible light, infrared or ultraviolet, X-rays} - A61L 2430/00: Materials or treatment for tissue regeneration - D10B 2201/01: Natural vegetable fibres - D10B 2211/01: Natural animal fibres, e.g. keratin fibres - Y10T 428/2967: Synthetic resin or polymer - Y10T 428/298: Physical dimension - D01D: MECHANICAL METHODS OR APPARATUS IN THE MANUFACTURE OF ARTIFICIAL FILAMENTS, THREADS, FIBRES, BRISTLES OR RIBBONS - 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) - D01F: CHEMICAL FEATURES IN THE MANUFACTURE OF ARTIFICIAL FILAMENTS, THREADS, FIBRES, BRISTLES OR RIBBONS; APPARATUS SPECIALLY ADAPTED FOR THE MANUFACTURE OF CARBON FILAMENTS - D06M: TREATMENT, NOT PROVIDED FOR ELSEWHERE IN CLASS D06, OF FIBRES, THREADS, YARNS, FABRICS, FEATHERS OR FIBROUS GOODS MADE FROM SUCH MATERIALS - D10B: INDEXING SCHEME ASSOCIATED WITH SUBLASSES OF SECTION D, RELATING TO TEXTILES - Y10T: TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION ## Abstract The presently disclosed subject matter provides a scalable and electrostretching approach for generating microfibers exhibiting uniaxial alignment from polymer solutions. Such microfibers can be generated from a variety of natural polymers or synthetic polymers. The hydrogel microfibers can be used for controlled release of bioactive agents. The internal uniaxial alignment exhibited by the presently disclosed fibers provides improved mechanical properties to microfibers, contact guidance cues and induces alignment for cells seeded on or within the microfibers. ## Claims ### Claim 1 A method for preparing a hydrogel microfiber having a uniaxial internal alignment, the method comprising: (a) providing at least one starting aqueous solution comprising one or more polymers; (b) applying an electrical potential to the at least one starting aqueous solution sufficient to initiate a jet stream of polymer solution; and (c) mechanically stretching the jet stream of polymer solution during or after collecting the jet stream of polymer solution in a collection bath comprising a stabilizing solution, wherein the collection bath is positioned at a separation distance between about 3 cm to about 6 cm such that the jet stream of polymer solution is collected before it is accelerated by an electrical field created by the applied electrical potential, wherein (i) the collection bath comprises a stationary collection plate, and wherein the jet stream of polymer solution is deposited on the stationary collection plate using a back and forth motion to mechanically stretch the jet stream of polymer solution as it is deposited on the stationary collection plate; or (ii) the collection bath comprises a stationary collection plate, and wherein the jet stream of polymer solution is deposited on the stationary collection plate using a back and forth motion to mechanically stretch the jet stream of polymer solution as it is deposited on the stationary collection plate. ### Claim 2 (depends on 1) The method of claim 1, wherein the one or more polymers comprise a natural polymer. ### Claim 3 (depends on 2) The method of claim 2, wherein the natural polymer is selected from the group consisting of water soluble polysaccharides, proteins, and combinations or blends thereof. ### Claim 4 (depends on 2) The method of claim 2, wherein the natural polymer is selected from the group consisting of one or more of alginate, fibrinogen, gelatin, collagen, hyaluronic acid, chitosan, chondroitin sulfate, dextran sulfate, heparin, heparan sulfate, functionalized derivatives thereof, and combinations or blends thereof. ### Claim 5 (depends on 1) The method of claim 1, wherein the one or more polymers comprise a synthetic polymer. ### Claim 6 (depends on 5) The method of claim 5, wherein the synthetic polymer is selected from the group consisting of a polyester and a polyamide. ### Claim 7 (depends on 6) The method of claim 6, wherein the polyester is selected from the group consisting of polylactic acid and poly(lactic-co-glycolic) acid. ### Claim 8 (depends on 5) The method of claim 5, wherein the synthetic polymer is selected from the group consisting of a polyacrylate, a poly(vinyl alcohol), a poly(ethylene glycol), functionalized derivatives thereof, and combinations or blends thereof. ### Claim 9 (depends on 1) The method of claim 1, wherein the at least one starting aqueous solution further comprises a thickening agent capable of increasing a viscosity of the jet stream of polymer solution. ### Claim 10 (depends on 9) The method of claim 9, wherein the thickening agent comprises polyethylene glycol (PEG). ### Claim 11 (depends on 1) The method of claim 1, further comprising crosslinking the hydrogel microfiber. ### Claim 12 (depends on 11) The method of claim 11, wherein the crosslinking, selected from the group consisting of ionic crosslinking, ultraviolet crosslinking, enzymatic crosslinking, and a chemical crosslinking reaction. ### Claim 13 (depends on 11) The method of claim 11, comprising adding a crosslinking agent to the at least one starting aqueous solution comprising one or more polymers. ### Claim 14 (depends on 11) The method of claim 11, comprising adding a crosslinking agent to the jet stream of polymer solution after the jet stream of polymer solution is initiated by the applied electrical potential. ### Claim 15 (depends on 11) The method of claim 11, comprising adding a crosslinking agent to the collection bath. ### Claim 16 (depends on 1) The method of claim 1, wherein the electrical potential has a range from about 2 kV to about 6 kV. ### Claim 17 (depends on 1) The method of claim 1, wherein the stabilizing solution comprises a solvent in which the jet stream of polymer solution is insoluble and precipitates in the stabilizing solution. ### Claim 18 (depends on 17) The method of claim 17, wherein the jet stream of polymer solution comprises an aqueous solution and one or more water-soluble polymers and the stabilizing solution comprises an organic solvent. ### Claim 19 (depends on 1) The method of claim 1, further comprising elongating the hydrogel microfiber by applying mechanical stress along the uniaxial internal alignment thereof, and drying the hydrogel microfiber. ### Claim 20 (depends on 1) The method of claim 1, further comprising combining multiple hydrogel microfibers to form a fiber bundle. ### Claim 21 (depends on 1) The method of claim 1, wherein: (a) the at least one starting aqueous solution comprises a blend of two different polymers; or (b) two starting aqueous solutions are provided, wherein each starting aqueous solution comprises a different polymer; and the hydrogel microfiber comprises a bicomponent fiber having a core and a sheath. ### Claim 22 (depends on 1) The method of claim 1, further comprising adding one or more bioactive agents to the at least one starting aqueous solution. ### Claim 23 (depends on 1) The method of claim 1, further comprising depositing one or more bioactive agents on the hydrogel microfiber after it is formed. ### Claim 24 (depends on 1) The method of claim 1, further comprising adding one or more cells to the at least one starting aqueous solution. ### Claim 25 (depends on 1) The method of claim 1, further comprising seeding the hydrogel microfiber with one or more cells on a surface of the hydrogel microfiber after it is formed.