Department of Chemistry, University of Idaho, Moscow, ID 83844, USA.
Department of Chemical and Biological Engineering, University of Idaho, Moscow, ID 83844, USA.
Biomater Sci. 2021 Aug 21;9(16):5508-5518. doi: 10.1039/d1bm00603g. Epub 2021 Jul 7.
Polyampholyte hydrogels are attractive materials for tissue engineering scaffolds as they offer a wide variety of features including nonfouling, selective protein delivery, and tunable physical characteristics. However, to improve the potential performance of these materials for in vivo applications, there is a need for a higher diversity of zwitterionic cross-linker species to replace commonly used ethylene glycol (EG) based chemistries. Towards this end, the synthesis of a dipeptide based zwitterionic cross-linker, N-Ser-Ser-C dimethacrylate (S-S) from N-Boc-l-serine is presented. The strategy utilized a convergent coupling of methacrylated serine partners followed by careful global deprotection to yield the zwitterionic cross-linker with good overall yields. This novel cross-linker was incorporated into a polyampholyte hydrogel and its physical properties and biocompatibility were compared against a polyampholyte hydrogel synthesized with an EG-based cross-linker. The S-S cross-linked hydrogel demonstrated excellent nonfouling performance, while promoting enhanced cellular adhesion to fibrinogen delivered from the hydrogel. Therefore, the results suggest that the S-S cross-linker will demonstrate superior future performance for in vivo applications.
聚两性电解质水凝胶作为组织工程支架材料具有很大的吸引力，因为它们具有多种特性，包括非粘性、选择性蛋白质输送和可调物理特性。然而，为了提高这些材料在体内应用中的潜在性能，需要更高多样性的两性离子交联剂种类来取代常用的乙二醇（EG）基化学物质。为此，本研究从 N-Boc-l-丝氨酸合成了一种二肽基两性离子交联剂 N-Ser-Ser-C 二甲基丙烯酸酯（S-S）。该策略利用了 methacrylated 丝氨酸伴侣的会聚偶联，然后进行仔细的全局脱保护，以得到具有良好总收率的两性离子交联剂。将这种新型交联剂掺入聚两性电解质水凝胶中，并将其物理性质和生物相容性与用 EG 基交联剂合成的聚两性电解质水凝胶进行了比较。S-S 交联水凝胶表现出优异的抗污染性能，同时促进了从水凝胶中输送的纤维蛋白原的细胞粘附增强。因此，结果表明 S-S 交联剂将在体内应用中表现出优异的性能。
