Synthesis of a zwitterionic N-Ser-Ser-C dimethacrylate cross-linker and evaluation in polyampholyte hydrogels

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.

Automated summary

Polyampholyte hydrogels are promising materials for tissue engineering scaffolds, offering nonfouling properties, selective protein delivery, and tunable physical characteristics. A novel dipeptide-based zwitterionic cross-linker, N-Ser-Ser-C dimethacrylate, was synthesized to improve the biocompatibility and cellular adhesion of the hydrogel, showing superior nonfouling performance and enhanced cellular adhesion to fibrinogen.