School of Chemical Engineering and Technology, Tianjin University , Tianjin 300072, P. R. China.
Tianjin Key Laboratory of Biomedical Materials, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences & Peking Union Medical College , Tianjin 300192, P. R. China.
ACS Appl Mater Interfaces. 2016 Jun 22;8(24):15710-23. doi: 10.1021/acsami.6b03098. Epub 2016 Jun 13.
In this work, a novel starch-based zwitterionic copolymer, starch-graft-poly(sulfobetaine methacrylate) (ST-g-PSBMA), was synthesized via Atom Transfer Radical Polymerization. Starch, which formed the main chain, can be degraded completely in vivo, and the pendent segments of PSBMA endowed the copolymer with excellent protein resistance properties. This ST-g-PSBMA copolymer could self-assemble into a physical hydrogel in normal saline, and studies of the formation mechanism indicated that the generation of the physical hydrogel was driven by electrostatic interactions between PSBMA segments. The obtained hydrogels were subjected to detailed analysis by scanning electron microscopy, swelling ratio, protein resistance, and rheology tests. Toxicity and hemolysis analysis demonstrated that the ST-g-PSBMA hydrogels possess excellent biocompatibility and hemocompatibility. Moreover, the cytokine secretion assays (IL-6, TNF-α, and NO) confirmed that ST-g-PSBMA hydrogels had low potential to trigger the activation of macrophages and were suitable for in vivo biomedical applications. On the basis of these in vitro results, the ST-g-PSBMA hydrogels were implanted in SD rats. The tissue responses to hydrogel implantation and the hydrogel degradation in vivo were determined by histological analysis (Hematoxylin and eosin, Van Gieson, and Masson's Trichrome stains). The results presented in this study demonstrate that the physical cross-linking, starch-based zwitterionic hydrogels possess excellent protein resistance, low macrophage-activation properties, and good biocompatibility, and they are a promising candidate for an in vivo biomedical application platform.
在这项工作中，通过原子转移自由基聚合合成了一种新型的基于淀粉的两性离子共聚体，淀粉接枝聚（磺基甜菜碱甲基丙烯酸酯）（ST-g-PSBMA）。作为主链的淀粉可以在体内完全降解，而 PSBMA 的支链赋予共聚物优异的抗蛋白质性质。这种 ST-g-PSBMA 共聚物可以在生理盐水中自组装成物理水凝胶，形成机制的研究表明，物理水凝胶的产生是由 PSBMA 段之间的静电相互作用驱动的。通过扫描电子显微镜、溶胀比、抗蛋白质性和流变学测试对获得的水凝胶进行了详细分析。毒性和溶血分析表明，ST-g-PSBMA 水凝胶具有优异的生物相容性和血液相容性。此外，细胞因子分泌测定（IL-6、TNF-α 和 NO）证实 ST-g-PSBMA 水凝胶具有低的激活巨噬细胞的潜力，适用于体内生物医学应用。基于这些体外结果，将 ST-g-PSBMA 水凝胶植入 SD 大鼠体内。通过组织学分析（苏木精和伊红、Van Gieson 和 Masson 三色染色）确定水凝胶植入物的组织反应和体内水凝胶降解。本研究结果表明，物理交联的基于淀粉的两性离子水凝胶具有优异的抗蛋白质性质、低的巨噬细胞激活特性和良好的生物相容性，是体内生物医学应用平台的有前途的候选物。
