Dong Dianyu, Li Junjie, Cui Man, Wang Jinmei, Zhou Yuhang, Luo Liu, Wei Yufei, Ye Lei, Sun Hong, Yao Fanglian
School of Chemical Engineering and Technology, Tianjin University , Tianjin 300072, China.
Department of Advanced Interdisciplinary Studies, Institute of Basic Medical Sciences and Tissue Engineering Research Center, Academy of Military Medical Sciences , Beijing 100850, China.
ACS Appl Mater Interfaces. 2016 Feb;8(7):4442-55. doi: 10.1021/acsami.5b12141. Epub 2016 Feb 9.
Three-dimensional (3D) cell encapsulation in hydrogel provides superb methods to investigate the biochemical cues in directing cellular fate and behaviors outside the organism, the primary step of which is to establish suitable "blank platform" to mimic and simplify native ECM microenvironment. In this study, zwitterionic starch-based "clickable" hydrogels were fabricated via a "copper- and light- free" Michael-type "thiol-ene" addition reaction between acylated-modified sulfobetaine-derived starch (SB-ST-A) and dithiol-functionalized poly(ethylene glycol) (PEG-SH). By incorporating antifouling SB-ST and PEG, the hydrogel system would be excellently protected from nontarget protein adsorption to act as a "blank platform". The hydrogels could rapidly gel under physiological conditions in less than 7 min. Dynamic rheology experiments suggested the stiffness of the hydrogel was close to the native tissues, and the mechanical properties as well as the gelation times and swelling behaviors could be easily tuned by varying the precursor proportions. The protein and cell adhesion assays demonstrated that the hydrogel surface could effectively resist nonspecific protein and cell adhesion. The degradation study in vitro confirmed that the hydrogel was biodegradable. A549 cells encapsulated in the hydrogel maintained high viability (up to 93%) and started to proliferate in number and extend in morphology after 2 days' culture. These results indicated the hydrogel presented here could be a potential candidate as "blank platform" for 3D cell encapsulation and biochemical cues induced cellular behavior investigation in vitro.
水凝胶中的三维（3D）细胞封装提供了卓越的方法来研究引导细胞在机体外命运和行为的生化线索，其首要步骤是建立合适的“空白平台”以模拟和简化天然细胞外基质（ECM）微环境。在本研究中，两性离子淀粉基“可点击”水凝胶通过酰化改性磺基甜菜碱衍生淀粉（SB-ST-A）与二硫醇官能化聚乙二醇（PEG-SH）之间的“无铜无光照”迈克尔型“硫醇-烯”加成反应制备而成。通过引入具有抗污性能的SB-ST和PEG，水凝胶体系能得到很好的保护，免受非靶向蛋白质吸附，从而充当“空白平台”。该水凝胶在生理条件下能在不到7分钟内快速凝胶化。动态流变学实验表明，水凝胶的刚度接近天然组织，并且通过改变前驱体比例可以轻松调节其力学性能、凝胶化时间和溶胀行为。蛋白质和细胞黏附试验表明，水凝胶表面能有效抵抗非特异性蛋白质和细胞黏附。体外降解研究证实该水凝胶具有生物可降解性。封装在水凝胶中的A549细胞保持了较高的活力（高达93%），在培养2天后开始数量增殖且形态伸展。这些结果表明，本文介绍的水凝胶可能是作为用于3D细胞封装和体外生化线索诱导细胞行为研究的“空白平台”的潜在候选材料。
