title: In situ cross-linkable hydrogel of hyaluronan produced via copper-free click chemistry.
abstract: Injectable hydrogels are useful in biomedical applications. We have synthesized hyaluronic acids chemically modified with azide groups (HA-A) and cyclooctyne groups (HA-C), respectively. Aqueous HA-A and HA-C solutions were mixed using a double-barreled syringe to form a hydrogel via strain-promoted [3 + 2] cycloaddition without any catalyst at physiological conditions. The hydrogel slowly degraded in PBS over 2 weeks, which was accelerated to 9 days by hyaluronidase, while it rapidly degraded in a cell culture media with fetal bovine serum within 4 days. Both HA-A and HA-C showed good biocompatibility with fibroblast cells in vitro. They were administered using the double-barreled syringe into mice subcutaneously and intraperitoneally. Residue of the hydrogel was cleared 21 days after subcutaneous administration, while it was cleared 7 days after intraperitoneal administration. This injectable HA hydrogel is expected to be useful for tissue engineering and drug delivery systems utilizing its orthogonality.
authors.affiliation: Department of Chemical System Engineering, The University of Tokyo , 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Takahashi
authors.forename: Yukimitsu
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Takashi
authors.initials: T
authors.lastname: Suhara
authors.forename: Kiyohiko
authors.initials: K
authors.lastname: Omichi
authors.forename: Atsushi
authors.initials: A
authors.lastname: Shimizu
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Hasegawa
authors.forename: Norihiro
authors.initials: N
authors.lastname: Kokudo
authors.forename: Seiichi
authors.initials: S
authors.lastname: Ohta
authors.forename: Taichi
authors.initials: T
authors.lastname: Ito
mesh_terms: D000480:Alkynes / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D001386:Azides / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D001672:Biocompatible Materials / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D057930:Click Chemistry; D003300:Copper; D003432:Cross-Linking Reagents / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D003500:Cyclization; D034242:Cyclooctanes / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006820:Hyaluronic Acid / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D006821:Hyaluronoglucosaminidase / Q000737:chemistry / Q000378:metabolism; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D015394:Molecular Structure; D041681:NIH 3T3 Cells; D013329:Structure-Activity Relationship
chemical_list: D000480:Alkynes; D001386:Azides; D001672:Biocompatible Materials; D003432:Cross-Linking Reagents; D034242:Cyclooctanes; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D003300:Copper; D006820:Hyaluronic Acid; D006821:Hyaluronoglucosaminidase