Department of Chemical System Engineering, The University of Tokyo , 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.
Biomacromolecules. 2013 Oct 14;14(10):3581-8. doi: 10.1021/bm4009606. Epub 2013 Sep 17.
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.
可注射水凝胶在生物医学应用中很有用。我们分别合成了带有叠氮基团（HA-A）和环辛炔基团（HA-C）的化学修饰透明质酸。在生理条件下，使用双筒注射器将透明质酸 A 和透明质酸 C 的水溶液混合，通过应变促进的[3+2]环加成形成水凝胶，无需任何催化剂。水凝胶在 PBS 中缓慢降解，2 周内被透明质酸酶加速至 9 天，而在含胎牛血清的细胞培养基中 4 天内迅速降解。HA-A 和 HA-C 均在体外与成纤维细胞表现出良好的生物相容性。它们通过双筒注射器皮下和腹腔内给药。皮下给药 21 天后，水凝胶的残留被清除，而腹腔内给药 7 天后被清除。这种可注射的 HA 水凝胶有望用于组织工程和药物输送系统，利用其正交性。
