School of Materials Science, Japan Advanced Institute of Science and Technology, 1-1 Asahidai, Nomi, Ishikawa 923-1292, Japan; Department of Chemistry, Faculty of Science, Chulalongkorn University, 254 Phayathai Road, Pathumwan, Bangkok 10330, Thailand.
Advanced NMR Application and Platform Team, NMR Research and Collaboration Group, NMR Science and Development Division, RIKEN SPring-8 Center, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.
Carbohydr Polym. 2019 Jan 15;204:131-141. doi: 10.1016/j.carbpol.2018.09.081. Epub 2018 Oct 3.
The objective of this study is to control and elucidate the mechanism of molecular degradation in a polysaccharide hydrogel. Glycidyl methacrylate (GMA) immobilized dextran (Dex-GMA) was oxidized by periodate to introduce aldehyde groups (oxidized Dex-GMA). The hydrogel was formed by the addition of dithiothreitol to the oxidized Dex-GMA solution through thiol Michael addition with the preservation of the aldehyde group for degradation points. It was experimentally determined that the degradation of this hydrogel can be controlled by the addition of amino groups and the speed of degradation can be controlled independently of mechanical properties because crosslinking and degradation points are different. In addition, the molecular mechanism of the crosslinking between the thiol and aldehyde groups was found to control the degradation of dextran derivatives. It is expected that these results will be beneficial in the design of polymer materials in which the speed of degradation can be precisely controlled. In addition, the cytotoxicity of oxidized Dex-GMA was approximately 3000 times lower than that of glutaraldehyde. The low cytotoxicity of the aldehyde in oxidized Dex-GMA was the likely reason for the harmless functionalized polysaccharide material. Possible future clinical applications include cell scaffolds in regenerative medicine and carriers for drug delivery systems.
本研究的目的是控制和阐明多糖水凝胶中分子降解的机制。通过高碘酸盐将甲基丙烯酰基缩水甘油（GMA）固定化在葡聚糖（Dex-GMA）上，以引入醛基（氧化的 Dex-GMA）。通过将二硫苏糖醇（DTT）添加到氧化的 Dex-GMA 溶液中，通过硫醇迈克尔加成反应形成水凝胶，同时保留醛基作为降解点。实验确定，通过添加氨基可以控制这种水凝胶的降解，并且可以独立于机械性能来控制降解速度，因为交联点和降解点是不同的。此外，还发现了巯基和醛基之间的交联的分子机制，可以控制葡聚糖衍生物的降解。预计这些结果将有助于设计可以精确控制降解速度的聚合物材料。此外，氧化的 Dex-GMA 的细胞毒性比戊二醛低约 3000 倍。氧化的 Dex-GMA 中醛基的低细胞毒性可能是无害功能化多糖材料的原因。可能的未来临床应用包括再生医学中的细胞支架和药物输送系统的载体。
