# US 2019/0167845 A1 · In situ tissue engineering > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2019/0167845 A1 - Document ID: US20190167845A1 - Status: Published application - Kind: A1 - Application number: 16/263,916 - Filed: 2019-01-31 - Published: 2019-06-06 - Earliest claimed: 2014-06-17 - Assignees: Academisch Ziekenhuis Leiden; Xeltis AG; Universiteit Maastricht - Applicants: Academisch Ziekenhuis Leiden; Xeltis B.V.; Universiteit Maastricht - Inventors: Joris Ivo Rotmans; Tonia Caroline Rothuizen; Lorenzo Moroni; Clemens Antoni Van Blitterswijk; Febriyani Fiain Rochel Damanik; Tom Lavrijsen; Martijn Antonius Johannes Cox; Antonius Johannes Rabelink - Web page: https://patentgrep.com/patent/US20190167845A1 ## CPC - A61L 27/34: Macromolecular materials - A61L 27/18: obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds - A61L 27/36: containing ingredients of undetermined constitution or reaction products thereof {, e.g. transplant tissue, natural bone, extracellular matrix (isolated natural compounds, e.g. collagen A61L27/24)} - A61L 27/507: {for artificial blood vessels (apparatus for applying cells on a blood vessel prosthesis A61F2/062)} - A61L 27/54: Biologically active materials, e.g. therapeutic substances {(A61L27/227 takes precedence)} - A61L 27/56: Porous materials, {e.g. foams or sponges} - A61L 27/58: Materials at least partially resorbable by the body - A61L 2300/414: Growth factors - A61L 2400/12: Nanosized materials, e.g. nanofibres, nanoparticles, nanowires, nanotubes; Nanostructured surfaces - A61L 2430/22: for reconstruction of hollow organs, e.g. bladder, esophagus, urether, uterus - A61L 2430/34: for soft tissue 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 The present disclosure relates to in situ tissue engineering, more specifically in situ vascular tissue engineering with the aim of providing a tissue structure which can be used e.g. as a substitute blood vessel or as a blood vessel functioning as cannulation site in hemodialysis. In particular, the disclosure involves tissue structure formation around a subcutaneously implanted synthetic rod. In addition, the disclosure involves a method for producing said synthetic rod. ## Claims ### Claim 1 A device configured to provide for a tissue structure by eliciting a foreign body response, wherein the device comprises a polymer capable of eliciting a foreign body response, wherein a surface of the device has a root mean square roughness (Rq) of at least 100 nm, and wherein the device is not at least partially in a form of a rod. ### Claim 2 (depends on 1) The device according to claim 1, wherein the device is at least partially in a form chosen from the group consisting of sheet, sphere, and form configured to result in a tissue structure resembling a hollow organ. ### Claim 3 (depends on 1) The device according to claim 1, wherein the eliciting of a foreign body response results in encapsulation of the device by the tissue structure. ### Claim 4 (depends on 1) The device according to claim 1, wherein the polymer capable of eliciting a foreign body response is chosen from the group consisting of polyester, polycarbonate, poly(orthoester), polyphosphoester, polyanhydride, polyphosphazene, polyhydroxyalkanoate, polyvinylalcohol, polypropylenefumarate, polyterephtalate or a copolymer of one or more of the group or a poly(ethylene oxide terephthalate)-poly(butylene terephthalate) copolymer. ### Claim 5 (depends on 1) The device according to claim 1, wherein an outer surface of the device has pores. ### Claim 6 (depends on 1) The device according to claim 1, wherein an outer surface of the device has a wettability characterized by a contact angle of at least 75° as measured by captive bubble method. ### Claim 7 (depends on 1) The device according to claim 1, wherein the root mean square roughness (Rq), a wettability, and/or pores are obtainable by exposure to halocarbon solvent or chemical etching. ### Claim 8 (depends on 1) The device according to claim 1, wherein the device comprises a recess within 30 mm of one or both longitudinal ends of the device and/or wherein an edge at one or both longitudinal ends of the device is rounded. ### Claim 9 (depends on 1) The device according to claim 1, wherein the device is bent within 50 mm from one or both longitudinal ends of the device. ### Claim 10 (depends on 1) The device according to claim 1, wherein the device is at least partially coated with an extracellular matrix protein and/or a growth factor. ### Claim 11 (depends on 1) The device according to claim 1, wherein the device has a length of 30-800 mm. ### Claim 12 (depends on 1) The device according to claim 1, wherein the device is suitable for subcutaneous implantation and/or wherein the device is able to elicit a foreign body response when inserted subcutaneously in a human or animal body. ### Claim 13 (depends on 1) A method for producing a device according to claim 1, wherein the method comprises: a) providing an apparatus comprising: a mold cavity which is at least partly in a form of the device according to claim 1, wherein the form is defined by U-shaped or indented inner surfaces of at least two mold parts; b) allowing fluid poly(ethylene oxide terephthalate)-poly(butylene terephthalate) copolymer to fill at least part of the at least one form of the mold cavity; c) allowing the copolymer to solidify; d) separating the at least two mold parts from the solidified copolymer to obtain at least one device in a form of the device according to claim 1; and e) exposing the at least one obtained device to chloroform and/or dichloromethane, wherein the device comprises a poly(ethylene oxide terephthalate)-poly(butylene terephthalate) copolymer, and wherein the surface of the device has a root mean square roughness (Rq) of at least 100 nm. ### Claim 14 (depends on 13) The method according to claim 13, wherein step e) exposes the at least one obtained device 5-15 seconds to chloroform and/or dichloromethane. ### Claim 15 A method for providing a tissue structure, wherein the method comprises the steps of: placing a device comprising a polymer capable of eliciting a foreign body response, wherein the device is not at least partially in a form of a rod, and wherein a surface of the device has a root mean square roughness (Rq) of at least 100 nm, into a subcutaneous space of a human or animal body to allow a tissue structure to form on the device by eliciting a foreign body response. ### Claim 16 (depends on 15) The method according to claim 15, wherein the device is at least partially in a form chosen from the group consisting of sheet, sphere, and form configured to result in a tissue structure resembling a hollow organ. ### Claim 17 (depends on 15) The method according to claim 15, wherein the eliciting of a foreign body response results in encapsulation of the device by the tissue structure. ### Claim 18 (depends on 15) The method according to claim 15, wherein the method comprises a further step of covering the tissue structure with a biodegradable sheet. ### Claim 19 (depends on 15) The method according to claim 15, wherein the method comprises a further step of connecting the tissue structure to a vein, artery and/or artificial kidney. ### Claim 20 (depends on 15) The method according to claim 15, wherein the method comprises a further step of employing the tissue structure as a bladder, ureter, urethra, or blood vessel. ### Claim 21 (depends on 1) The device according to claim 1, wherein the surface of the device has a root mean square roughness (Rq) of at least 150 nm. ### Claim 22 (depends on 4) The device according to claim 4, wherein the polymer is according to a formula A/B/C, wherein A, a molecular weight of an initial polyethylene glycol (PEG) used in the copolymer reaction, is between 200-400; B, a wt. % of poly(ethylene oxide terephthalate) in the copolymer, is 40-70; and C, a wt. % of poly(butylene terephthalate) in the copolymer, is 30-60. ### Claim 23 (depends on 5) The device according to claim 5, wherein a pore density is 10-100 pores per 100 μm2; and/or an average pore diameter is 0.3-2.0 μm. ### Claim 24 (depends on 7) The device according to claim 7, wherein the root mean square roughness (Rq), the wettability and/or the pores are obtainable by chemical etching by exposing the surface of the device to a halocarbon or an organic solvent. ### Claim 25 (depends on 14) The device according to claim 14, wherein the halocarbon or an organic solvent is chloroform and/or dichloromethane. ### Claim 26 (depends on 11) The device according to claim 11, wherein the device has a length of 50-150 mm and/or a diameter of 6-10 mm. ### Claim 27 (depends on 15) The method for producing a device according to claim 15, wherein the surface of the device has a root mean square roughness (Rq) of at least 150 nm. ### Claim 28 (depends on 1, 15) The method for providing a tissue structure according to claim 15, wherein the method comprises the steps of: placing the device according to claim 1 into a subcutaneous space of a human or animal body for a period of 1-6 weeks to allow a tissue structure to form on the device. ### Claim 29 (depends on 9) The device according to claim 9, wherein the device has an S-shape. ### Claim 30 (depends on 22) The device according to claim 22, wherein the molecular weight of the initial polyethylene glycol (PEG) used in the copolymer reaction is between 275-325; wherein the wt. % of poly(ethylene oxide terephthalate) in the copolymer is 50-60; and wherein the wt. % of poly(butylene terephthalate) in the copolymer, is 40-50. ### Claim 31 (depends on 1) The device according to claim 1, wherein the tissue structure forms the basis for a hollow tissue structure. ### Claim 32 (depends on 31) The device according to claim 31, wherein the hollow tissue structure resembles a blood vessel, an ureter, or a bladder. ### Claim 33 (depends on 2) The device according to claim 2, wherein the device as a whole is in a form chosen from the group of sheet, sphere, and form configured to result in a tissue structure resembling a hollow organ. ### Claim 34 (depends on 2) The device according to claim 2, wherein the sheet is of 1-5 mm thickness.