Shirahama Hitomi, Lee Bae Hoon, Tan Lay Poh, Cho Nam-Joon
School of Materials Science and Engineering, Nanyang Technological University, 50 Nanyang Avenue, 639798 Singapore.
School of Chemical and Biomedical Engineering, Nanyang Technological University, 62 Nanyang Drive, 637459 Singapore.
Sci Rep. 2016 Aug 9;6:31036. doi: 10.1038/srep31036.
Gelatin-methacryloyl (GelMA) is one of the most commonly used photopolymerizable biomaterials in bio-applications. However, GelMA synthesis remains suboptimal, as its reaction parameters have not been fully investigated. The goal of this study is to establish an optimal route for effective and controllable GelMA synthesis by systematically examining reaction parameters including carbonate-bicarbonate (CB) buffer molarity, initial pH adjustment, MAA concentration, gelatin concentration, reaction temperature, and reaction time. We employed several analytical techniques in order to determine the degree of substitution (DS) and conducted detailed structural analysis of the synthesized polymer. The results enabled us to optimize GelMA synthesis, showing the optimal conditions to balance the deprotonation of amino groups with minimizing MAA hydrolysis, which led to nearly complete substitution. The optimized conditions (low feed ratio of MAA to gelatin (0.1 mL/g), 0.25 M CB buffer at pH 9, and a gelatin concentration of 10-20%) enable a simplified reaction scheme that produces GelMA with high substitution with just one-step addition of MAA in one pot. Looking forward, these optimal conditions not only enable facile one-pot GelMA synthesis but can also guide researchers to explore the efficient, high methacrylation of other biomacromolecules.
明胶-甲基丙烯酰（GelMA）是生物应用中最常用的可光聚合生物材料之一。然而，GelMA的合成仍不尽人意，因为其反应参数尚未得到充分研究。本研究的目的是通过系统地考察包括碳酸盐-碳酸氢盐（CB）缓冲液摩尔浓度、初始pH调节、甲基丙烯酸（MAA）浓度、明胶浓度、反应温度和反应时间等反应参数，建立一条有效且可控的GelMA合成优化路线。我们采用了多种分析技术来测定取代度（DS），并对合成的聚合物进行了详细的结构分析。结果使我们能够优化GelMA的合成，显示出在使MAA水解最小化的同时平衡氨基去质子化的最佳条件，这导致了几乎完全取代。优化后的条件（MAA与明胶的低进料比（0.1 mL/g）、pH 9的0.25 M CB缓冲液和10-20%的明胶浓度）实现了一个简化的反应方案，只需在一锅法中一步加入MAA就能生产出高取代度的GelMA。展望未来，这些最佳条件不仅能实现简便的一锅法GelMA合成，还能指导研究人员探索其他生物大分子的高效、高甲基丙烯酰化反应。
