# US 9,750,845 B2 · Biodegradable nanocomposites with enhanced mechanical properties for soft tissue engineering > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 9,750,845 B2 - Document ID: US9750845B2 - Status: Granted - Kind: B2 - Application number: 14/083,071 - Filed: 2013-11-18 - Published: 2014-05-15 - Granted: 2017-09-05 - Earliest claimed: 2005-09-28 - Assignees: Northwestern University - Applicants: Northwestern University - Inventors: Guillermo Ameer; Antonio R. Webb - Web page: https://patentgrep.com/patent/US9750845B2 ## CPC - A61L 27/18: obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds - A61L 27/50: Materials characterised by their function or physical properties {, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials} - A61L 27/58: Materials at least partially resorbable by the body - A61K 9/0024: {Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue (compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L)} - A61K 31/74: Synthetic polymeric materials - A61K 31/765: Polymers containing oxygen - A61K 47/30: Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates - A61K 47/34: Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers (A61K47/10 takes precedence) - A61L 2400/12: Nanosized materials, e.g. nanofibres, nanoparticles, nanowires, nanotubes; Nanostructured surfaces - 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) - 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) ## Abstract The present invention is directed to a novel poly(diol citrates)-based nanocomposite materials created using completely biodegradable and biocompatible polymers that may be used in tissue engineering. More specifically, the specification describes methods and compositions for making and using nanocomposites comprised of citric acid copolymers and polymers including but not limited to poly(L-lactic acid) (PLLA) and poly(lactic-co-glycolic acid) (PLGA). ## Claims ### Claim 1 A method, comprising: (a) combining a poly(diol citrate) pre-polymer solution with a nanostructured poly(L-lactic acid) to form a mixture; (b) polymerizing the mixture to form a nanocomposite comprising polymerized poly(diol citrate) and nanostructured poly(L-lactic acid); (c) hydrolyzing the poly(L-lactic acid) during the polymerization step to form free carboxyl groups on the surface of the nanostructured poly(L-lactic acid); and (d) forming covalent bonds between the free carboxyl groups on the surface of the hydrolyzed poly(L-lactic acid) and the polymerized poly(diol citrate). ### Claim 2 (depends on 1) The method of claim 1 wherein said poly(diol citrate) comprises monomers of citric acid and a linear diol comprising between 2 and 20 carbons. ### Claim 3 (depends on 2) The method of claim 2, wherein said poly(diol citrate) comprises citric acid and 1,8-octanediol monomers. ### Claim 4 (depends on 2) The method of claim 2, wherein said poly(diol citrate) comprises citric acid and 1,10-decanediol monomers. ### Claim 5 (depends on 1) The method of claim 1, further comprising a step of removing solvent and/or water before the polymerizing step. ### Claim 6 (depends on 1) The method of claim 1 wherein said poly(diol citrate) comprises two different linear diol monomers. ### Claim 7 (depends on 1) The method of claim 1, wherein said nanostructured poly(L-lactic acid) is fabricated into nanofibers. ### Claim 8 (depends on 1) The method of claim 1, wherein said nanostructured poly(L-lactic acid) is formulated into nanoparticles. ### Claim 9 (depends on 1) The method of claim 1, further comprising forming mechanically interlocked chains between the polymerized poly(diol citrate) and nanostructured poly(L-lactic acid). ### Claim 10 (depends on 1) The method of claim 1, wherein the nanostructured poly(L-lactic acid) has nanopores and wherein the combining step further comprises impregnating the nanopores with the poly(diol citrate) pre-polymer solution. ### Claim 11 (depends on 10) The method of claim 10, wherein the nanopores are completely filled with the poly(diol citrate) pre-polymer solution. ### Claim 12 (depends on 1) The method of claim 1, wherein said poly(diol citrate) comprises two different linear diol monomers, and wherein the method further comprises controlling the Young's modulus of the formed nanocomposite by varying the ratio of the two different linear diol monomer. ### Claim 13 (depends on 1) A nanocomposite produced by the method of claim 1. ### Claim 14 (depends on 13) A substrate for use in tissue engineering comprising the nanocomposite of claim 13 formulated into a cell culture substrate. ### Claim 15 (depends on 14) The substrate of claim 14, wherein said substrate further comprises a surface modification. ### Claim 16 (depends on 13) A drug delivery device comprising a drug interspersed in the nanocomposite of claim 13.