# US 2019/0314554 A1 · Hydrogel precursors having nanoparticles > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2019/0314554 A1 - Document ID: US20190314554A1 - Status: Published application - Kind: A1 - Application number: 16/428,534 - Filed: 2019-05-31 - Published: 2019-10-17 - Earliest claimed: 2013-09-25 - Assignees: University of Kansas - Applicants: The University of Kansas - Inventors: Michael DETAMORE; Emily BECK; Stevin GEHRKE; Cory BERKLAND - Web page: https://patentgrep.com/patent/US20190314554A1 ## CPC - A61L 27/48: with macromolecular fillers - A61L 27/20: Polysaccharides - A61L 27/3817: {Cartilage-forming cells, e.g. pre-chondrocytes} - A61L 27/383: {Nerve cells, e.g. dendritic cells, Schwann cells} - A61L 27/3834: {Cells able to produce different cell types, e.g. hematopoietic stem cells, mesenchymal stem cells, marrow stromal cells, embryonic stem cells} - A61L 27/50: Materials characterised by their function or physical properties {, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials} - A61L 27/52: Hydrogels or hydrocolloids - A61L 27/54: Biologically active materials, e.g. therapeutic substances {(A61L27/227 takes precedence)} - A61L 2430/06: for cartilage reconstruction, e.g. meniscus - A61L 2430/32: for nerve reconstruction - 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) ## Abstract An implantable hydrogel precursor composition can include: a cross-linkable polymer matrix that is biocompatible; and a plurality of polymer particles in the cross-linkable polymer matrix. The cross-linkable polymer matrix can include a cross-linkable hyaluronic acid polymer that has cross-linkable functional groups. The hyaluronic acid polymer can be a methacrylated hyaluronic acid polymer. The methacrylated hyaluronic acid polymer can have a molecular weight from about 500 kDa to about 1.8 MDa. The polymer particles can include a cross-linked hyaluronic acid. The cross-linkable polymer matrix having the polymer particles has a yield stress. The cross-linkable polymer matrix having the polymer particles has shape retention at physiological temperatures. The composition can include live cells in the cross-linkable polymer matrix. The composition can include a biologically active agent in the cross-linkable polymer matrix. ## Claims ### Claim 1 A method of forming a hydrogel implant, comprising: providing an implantable hydrogel precursor composition that has a yield stress at zero shear rate, the implantable hydrogel precursor composition comprising: a cross-linkable polymer matrix that is biocompatible; and a plurality of polymer particles in the cross-linkable polymer matrix; implanting the hydrogel precursor composition into a body of a subject such that the hydrogel precursor composition has a shape and shape retention while in the body; and crosslinking the cross-linkable polymer matrix to form a hydrogel containing the plurality of polymer particles that has the shape. ### Claim 2 (depends on 1) The method of claim 1, further comprising shaping the hydrogel precursor composition to have the shape with shape retention while in the body. ### Claim 3 (depends on 2) The method of claim 2, further comprising: placing the hydrogel precursor in a defect in a tissue in the body; and crosslinking the cross-linkable polymer in the defect. ### Claim 4 (depends on 3) The method of claim 3, wherein while in the defect, the hydrogel precursor composition retains the shape without leaking or flowing out of the defect. ### Claim 5 (depends on 2) The method of claim 2, further comprising shaping the hydrogel precursor composition with an instrument to obtain the shape. ### Claim 6 (depends on 3) The method of claim 3, wherein the defect is in a cartilage tissue, a bone tissue, or a nerve tissue. ### Claim 7 (depends on 1) The method of claim 1, further comprising: placing cells within the hydrogel precursor composition; and performing the crosslinking with the cells within the cross-linking composition. ### Claim 8 (depends on 1) The method of claim 1, further comprising: providing a cross-linkable polymer matrix that is biocompatible; and mixing a plurality of polymer particles into the cross-linkable polymer matrix. ### Claim 9 (depends on 3) The method of claim 3, further comprising forming the defect in the tissue. ### Claim 10 (depends on 8) The method of claim 8, further comprising: providing a bioactive agent; and mixing the bioactive agent into the cross-linkable polymer matrix. ### Claim 11 (depends on 1) The method of claim 1, further comprising: regenerating bone with the hydrogel; regenerating cartilage with the hydrogel; or regenerating nerves with the hydrogel. ### Claim 12 (depends on 11) The method of claim 11, further comprising treating a full or partial thickness cartilage defect with the hydrogel. ### Claim 13 (depends on 1) The method of claim 1, wherein the cross-linkable polymer matrix includes a cross-linkable hyaluronic acid polymer that has cross-linkable functional groups. ### Claim 14 (depends on 13) The method of claim 13, wherein the hyaluronic acid polymer is a methacrylated hyaluronic acid polymer. ### Claim 15 (depends on 14) The method of claim 14, wherein the methacrylated hyaluronic acid polymer has a molecular weight from about 500 kDa to about 1.8 MDa. ### Claim 16 (depends on 1) The composition of claim 1, wherein the polymer particles include a cross-linked hyaluronic acid. ### Claim 17 (depends on 16) The method of claim 16, wherein the hyaluronic acid polymer particles have a molecular weight of about 10 kDa to about 20 kDa. ### Claim 18 (depends on 1) The method of claim 1, wherein the implantable hydrogel precursor composition comprises: a cross-linkable hyaluronic acid polymer having a cross-linkable functional group forming a cross-linkable polymer matrix that is biocompatible; and a plurality of polymer nanoparticles in the cross-linkable polymer matrix, wherein the polymer nanoparticles are cross-linked hyaluronic acid, wherein: the cross-linkable hyaluronic acid polymer is present from about 2% to about 10%; and the polymer nanoparticles are present from about 10% to about 40%. ### Claim 19 (depends on 18) The method of claim 18, wherein: the polymer nanoparticles have a molecular weight of about 10 kDa to about 20 kDa; the polymer nanoparticles have a particle size of about 10 nm to about 500 nm; and a ratio of cross-linkable hyaluronic acid polymer to polymer nanoparticles is from 1:15 to about 2:1. ### Claim 20 (depends on 18) The method of claim 18, wherein the implantable hydrogel precursor composition comprises: live cells; and/or a biologically active agent. ### Claim 21 (depends on 18) The method of claim 18, wherein the implantable hydrogel precursor composition comprises: a non-zero shear stress at a shear rate below 1 s−1; a shear stress of about 500 Pa to about 1000 Pa at 1 s−1 shear rate; a yield stress of at least about 400 Pa to about 800 Pa; and/or a storage modulus: about 400 Pa to about 1100 Pa at an initial phase, about 10 Pa to about 400 Pa at a disruption phase, and about 500 Pa to about 1200 Pa at a recovery phase.