# US 11,898,055 B2 · PEM layer-by-layer systems for coating substrates to improve bioactivity and biomolecule delivery > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 11,898,055 B2 - Document ID: US11898055B2 - Status: Granted - Kind: B2 - Application number: 17/495,543 - Filed: 2021-10-06 - Published: 2022-02-10 - Granted: 2024-02-13 - Earliest claimed: 2013-04-03 - Assignees: University of Pittsburgh—Of the Commonwealth System of Higher Education - Applicants: University of Pittsburgh—of the Commonwealth System of Higher Education - Inventors: Prashant N. Kumta; Sangeetha Kunjukunju; Nicole J. Ostrowski; Abhijit Roy; Boeun Lee; Madhumati Ramanathan - Web page: https://patentgrep.com/patent/US11898055B2 ## CPC - C09D 177/04: Polyamides derived from alpha-amino carboxylic acids (C09D177/10 takes precedence) - A61F 2/02: Prostheses implantable into the body - A61L 27/04: Metals or alloys - A61L 27/34: Macromolecular materials - A61L 27/54: Biologically active materials, e.g. therapeutic substances {(A61L27/227 takes precedence)} - A61L 27/58: Materials at least partially resorbable by the body - B05D 7/58: {No clear coat specified} - C09D 105/04: Alginic acid; Derivatives thereof - C09D 167/04: Polyesters derived from hydroxycarboxylic acids, e.g. lactones (C09D167/06 takes precedence) - A61F 2210/0076: multilayered, e.g. laminated structures - A61F 2310/00976: Coating or prosthesis-covering structure made of proteins or of polypeptides, e.g. of bone morphogenic proteins BMP or of transforming growth factors TGF - A61L 2300/608: having two or more layers - A61L 2420/08: Coatings comprising two or more layers - C09D: COATING COMPOSITIONS, e.g. PAINTS, VARNISHES OR LACQUERS; FILLING PASTES; CHEMICAL PAINT OR INK REMOVERS; INKS; CORRECTING FLUIDS; WOODSTAINS; PASTES OR SOLIDS FOR COLOURING OR PRINTING; USE OF MATERIALS THEREFOR (cosmetics A61K; processes for applying liquids or other fluent materials to surfaces, in general, B05D; staining wood B27K5/02; glazes or vitreous enamels C03C; natural resins, French polish, drying-oils, driers, turpentine, per se, C09F; polishing compositions other than French polish, ski waxes C09G; adhesives or use of materials as adhesives C09J; materials for sealing or packing joints or covers C09K3/10; materials for stopping leaks C09K3/12; processes for the electrolytic or electrophoretic production of coatings C25D) - A61F: FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS (dental prosthetics A61C) - 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) - B05D: PROCESSES FOR APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL (conveying articles or workpieces through baths of liquid B65G, e.g. B65G49/02) ## Abstract The invention relates to polyelectrolyte multilayer coatings and, methods for their preparation and application to substrates to enhance the bioactivity and corrosion protection of the substrates' surface. The invention is particularly suitable for coating substrates employed for medical applications, such as but not limited to medical implant devices for drug and/or biologics delivery in a patient. The substrate has a positive or negative charge. The polyelectrolyte multilayer coatings include at least a first polymer layer and a second polymer layer. The first polymer and second polymer have opposite charges. Each of the polymer layers is individually applied using a layer-by-layer such that an alternating charge multilayer coating is formed. ## Claims ### Claim 1 A coated medical implant device, comprising: a substrate selected from the group comprising magnesium metal, magnesium alloy, iron metal, iron alloy, ferrous metal and ferrous alloy; a pretreatment agent selected from the group consisting of alkali metal hydroxide, hydrogen fluoride, alkali metal carbonates, and mixtures thereof, applied to a surface of the substrate to form a charged substrate having a positive charge or a negative charge; a polyelectrolyte multilayer coating deposited on the charged substrate, comprising: a plurality of interfacing, individual polymer layers, comprising: at least one polymer layer comprising a first polymer and having a positive charge; and at least one polymer layer comprising a second polymer and having a negative charge; wherein an initial polymer layer of the plurality of interfacing, individual polymer layers is deposited on the charged substrate and has a charge opposite the charged substrate, and wherein an outer polymer layer of the plurality of interfacing, individual polymer layers forms an exterior surface of the charged substrate; fibronectin immobilized on the exterior surface; and an active substance, in addition to the fibronectin, deposited on the exterior surface of the charged substrate. ### Claim 2 (depends on 1) The device of claim 1, wherein the charged substrate is degradable. ### Claim 3 (depends on 1) The device of claim 1, wherein the first polymer and the second polymer are each selected from the group consisting of natural polymer, synthetic polymer and mixtures thereof. ### Claim 4 (depends on 1) The device of claim 1, wherein the first polymer and the second polymer are each selected from the group consisting of alginate, poly-L-lysine, poly(lactic-co-glycolic acid), polycaprolactone, poly(allylamine hydrochloride), polyacrylic acid, heparin, hyaluronic acid, polystyrene sulfonate, poly-L-glutamic acid, chitosan, polyethyleneimine, polydiallyldimethylammonium chloride and, mixtures and combinations thereof. ### Claim 5 (depends on 4) The device of claim 4, wherein the first polymer and the second polymer are each selected from the group consisting of alginate and a mixture of poly-L-lysine and poly(lactic-co-glycolic acid). ### Claim 6 (depends on 4) The device of claim 4, wherein the first polymer and the second polymer are each selected from the group consisting of polycaprolactone and poly(allylamine hydrochloride). ### Claim 7 (depends on 1) The device of claim 1, wherein the first polymer and the second polymer are each in the form of a solution and deposition of the polyelectrolyte multilayer coating on the charged substrate comprises individually dipping the charged substrate into each of the first polymer solution and the second polymer solution. ### Claim 8 (depends on 1) The device of claim 1, wherein the active substance is selected from the group consisting of drugs, biologic materials, growth factors, DNA, transfecting agents, living molecules and combinations thereof. ### Claim 9 (depends on 1) The device of claim 1, wherein the active substance is deposited on one or more of the plurality of interfacing, individual polymer layers in addition to being deposited on the exterior surface of the charged substrate. ### Claim 10 A coated medical implant device, comprising: a substrate selected from the group comprising magnesium metal, magnesium alloy, iron metal, iron alloy, ferrous metal and ferrous alloy; a pretreatment agent selected from the group consisting of alkali metal hydroxide, hydrogen fluoride, alkali metal carbonates, and mixtures thereof, applied to a surface of the substrate to form a charged substrate having a positive charge or a negative charge; a polyelectrolyte multilayer coating deposited on the charged substrate, comprising: a plurality of interfacing, individual polymer layers, comprising: one or more polymer layers having a positive charge; and one or more polymer layers having a negative charge, wherein an initial layer of the plurality of interfacing, individual polymer layers is deposited on the charged substrate and has a charge opposite the charged substrate, and wherein the plurality of interfacing, individual polymer layers has alternating layers of the one or more polymer layers having a positive charge and the one or more polymer layers having a negative charge; a chemical cross-linking agent deposited on an outer polymer layer forming a modified outer surface; fibronectin immobilized on the modified outer surface; and an active substance, in addition to the fibronectin, deposited on the modified outer surface. ### Claim 11 A method of preparing a coating medical implant device, comprising: selecting a substrate from the group comprising magnesium metal, magnesium alloy, iron metal, iron alloy, ferrous metal and ferrous alloy; applying a pretreatment agent selected from the group consisting of alkali metal hydroxide, hydrogen fluoride, alkali metal carbonates, and mixtures thereof, to a surface of the substrate to form a charged substrate having a positive charge or negative charge; and depositing a plurality of interfacing, individual polymer layers on the charged substrate to form a polyelectrolyte multilayer coating, comprising: depositing at least one polymer layer comprising a first polymer and having a positive charge; and depositing at least one polymer layer comprising a second polymer and having a negative charge, wherein an initial polymer layer of the plurality of interfacing, individual polymer layers is deposited on the charged substrate and has a charge opposite the charged substrate, and wherein an outer polymer layer of the plurality of interfacing, individual polymer layers forms an exterior surface of the charged substrate; immobilizing fibronectin on the exterior surface; and depositing an active substance, in addition to the fibronectin, on the exterior surface of the charged substrate. ### Claim 12 (depends on 11) The method of claim 11, wherein the depositing a plurality of interfacing, individual polymer layers comprises individually dipping the charged substrate into each of a first polymer solution and a second polymer solution. ### Claim 13 (depends on 11) The method of claim 11, further comprising depositing the active substance on one or more of the plurality of interfacing, individual polymer layers in addition to depositing on the exterior surface of the charged substrate. ### Claim 14 (depends on 11) The method of claim 11, further comprising depositing a chemical cross-linking agent on the outer polymer layer forming a modified exterior outer surface. ### Claim 15 (depends on 14) The method of claim 14, further comprising immobilizing the fibronectin on the modified exterior surface, in addition to the active substance.