In Situ Cross-Linkable Hydrogel of Hyaluronan Produced via Copper-Free Click Chemistry

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• 作者：Akira Takahashi ; Yukimitsu Suzuki ; Takashi Suhara ; Kiyohiko Omichi ; Atsushi Shimizu ; Kiyoshi Hasegawa ; Norihiro Kokudo ; Seiichi Ohta ; Taichi Ito
• 刊名：Biomacromolecules
• 出版年：2013
• 出版时间：October 14, 2013
• 年：2013
• 卷：14
• 期：10
• 页码：3581-3588
• 全文大小：501K
• 年卷期：v.14,no.10(October 14, 2013)
• ISSN：1526-4602

文摘

Injectable hydrogels are useful in biomedical applications. We have synthesized hyaluronic acids chemically modified with azide groups (HA鈥揂) and cyclooctyne groups (HA鈥揅), respectively. Aqueous HA鈥揂 and HA鈥揅 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鈥揂 and HA鈥揅 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.