RRC ID 44627
Author Takahashi A, Suzuki Y, Suhara T, Omichi K, Shimizu A, Hasegawa K, Kokudo N, Ohta S, Ito T.
Title In situ cross-linkable hydrogel of hyaluronan produced via copper-free click chemistry.
Journal Biomacromolecules
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.
Volume 14(10)
Pages 3581-8
Published 2013-10-14
DOI 10.1021/bm4009606
PMID 24004342
MeSH Alkynes / chemistry Alkynes / metabolism Alkynes / pharmacology Animals Azides / chemistry Azides / metabolism Azides / pharmacology Biocompatible Materials / chemistry Biocompatible Materials / metabolism Biocompatible Materials / pharmacology Cell Survival / drug effects Click Chemistry* Copper Cross-Linking Reagents / chemical synthesis* Cross-Linking Reagents / metabolism Cross-Linking Reagents / pharmacology Cyclization Cyclooctanes / chemistry Cyclooctanes / metabolism Cyclooctanes / pharmacology Dose-Response Relationship, Drug Fibroblasts / drug effects Fibroblasts / metabolism Hyaluronic Acid / chemistry* Hyaluronic Acid / metabolism Hyaluronic Acid / pharmacology Hyaluronoglucosaminidase / chemistry Hyaluronoglucosaminidase / metabolism Hydrogel, Polyethylene Glycol Dimethacrylate / chemical synthesis Hydrogel, Polyethylene Glycol Dimethacrylate / chemistry* Hydrogel, Polyethylene Glycol Dimethacrylate / metabolism Hydrogel, Polyethylene Glycol Dimethacrylate / pharmacology Injections, Intraperitoneal Injections, Subcutaneous Male Mice Mice, Inbred ICR Molecular Structure NIH 3T3 Cells Structure-Activity Relationship
IF 5.667
Times Cited 71
Human and Animal Cells