R&D Center for Membrane Technology and Department of Chemical Engineering, Chung Yuan Christian University, Jhong-Li, Taoyuan 320, Taiwan.
Biomacromolecules. 2010 Apr 12;11(4):1101-10. doi: 10.1021/bm100093g.
This work describes a novel tunable bioadhesive hydrogel of thermoresponsive N-isopropylacrylamide (NIPAAm) containing zwitterionic sulfobetaine methacrylate (SBMA). This novel hydrogel highly regulates general bioadhesive foulants through the adsorption of plasma proteins, the adhesion of human platelets and cells, and the attachment of bacteria. In this investigation, nonionic hydrogels of polyNIPAAm, zwitterionic hydrogels of polySBMA, and three copolymeric hydrogels of NIPAAm and SBMA (poly(NIPAAm-co-SBMA)) were prepared. The copolymeric hydrogels exhibited controllable temperature-dependent swelling behaviors and showed stimuli-responsive phase characteristics in the presence of salts. The interactions of these hydrogels with biomolecules and microorganisms were demonstrated by protein adsorption, cell adhesion, and bacterial attachment, which allowed us to evaluate their bioadhesive properties. An enzyme-linked immunosorbent assay (ELISA) with monoclonal antibodies was used to measure different plasma protein adsorptions on the prepared hydrogel surfaces. At a physiological temperature, the high content of the nonionic polyNIPAAm in poly(NIPAAm-co-SBMA) hydrogel exhibits a high protein adsorption due to the interfacial exposure of polyNIPAAm-rich hydrophobic domains. A relatively high content of polySBMA in poly(NIPAAm-co-SBMA) hydrogel exhibits reduced amounts of protein adsorption due to the interfacial hydration of polySBMA-rich hydrophilic segments. The attachment of platelets and the spreading of cells were only observed on polyNIPAAm-rich hydrogel surfaces. Interestingly, the incorporation of zwitterionic SBMA units into the polyNIPAAm gels was found to accelerate the hydration of the cell-cultured surfaces and resulted in more rapid cell detachment. Such copolymer gel surface was shown to be potentially useful for triggered cell detachment. In addition, the interactions of hydrogels with bacteria were also evaluated. The polySBMA-rich hydrogels exhibited evident antimicrobial properties when they were incubated with Gram-positive bacteria ( S. epidermidis ) and Gram-negative bacteria ( E. coli ). This work shows that the bioadhesive properties of poly(NIPAAm-co-SBMA) hydrogels can be effectively controlled via regulated nonionic and zwitterionic molar mass ratios. The tunable-bioadhesive behavior of temperature-sensitive poly(NIPAAm-co-SBMA) makes this biocompatible hydrogel appropriate for biomedical applications.
这项工作描述了一种新型的、可调节的温敏水凝胶，它由 N-异丙基丙烯酰胺（NIPAAm）和两性离子磺酸甜菜碱甲基丙烯酰胺（SBMA）组成。这种新型水凝胶可以通过吸附血浆蛋白、黏附人血小板和细胞以及附着细菌，对一般的生物黏附污染物进行高度调节。在这项研究中，制备了非离子型聚 N-异丙基丙烯酰胺（polyNIPAAm）水凝胶、两性离子型聚 SBMA 水凝胶和 NIPAAm 和 SBMA 的三种共聚水凝胶（poly（NIPAAm-co-SBMA））。共聚水凝胶表现出可控的温敏性溶胀行为，并在盐存在下表现出刺激响应的相特性。通过蛋白质吸附、细胞黏附和细菌附着来证明这些水凝胶与生物分子和微生物的相互作用，这使我们能够评估它们的生物黏附特性。用单克隆抗体进行酶联免疫吸附试验（ELISA），测量在制备的水凝胶表面上不同的血浆蛋白吸附。在生理温度下，由于富含 NIPAAm 的疏水性畴的界面暴露，高含量的非离子型聚 N-异丙基丙烯酰胺（polyNIPAAm）在 poly（NIPAAm-co-SBMA）水凝胶中表现出高蛋白质吸附。由于富含 SBMA 的亲水性段的界面水合作用，poly（NIPAAm-co-SBMA）水凝胶中相对高含量的 polySBMA 表现出减少的蛋白质吸附量。血小板的附着和细胞的铺展仅观察到在富含 NIPAAm 的水凝胶表面。有趣的是，将两性离子 SBMA 单元掺入聚 N-异丙基丙烯酰胺凝胶中被发现能加速细胞培养表面的水合作用，从而导致更快的细胞脱落。这种共聚物凝胶表面显示出潜在的有用的用于触发细胞脱落。此外，还评估了水凝胶与细菌的相互作用。当与革兰氏阳性菌（表皮葡萄球菌）和革兰氏阴性菌（大肠杆菌）孵育时，富含 polySBMA 的水凝胶表现出明显的抗菌性能。这项工作表明，通过调节非离子和两性离子摩尔质量比，可以有效地控制 poly（NIPAAm-co-SBMA）水凝胶的生物黏附特性。温度敏感的 poly（NIPAAm-co-SBMA）的可调生物黏附行为使这种生物相容性水凝胶适用于生物医学应用。
