Biodegradable Phosphocholine Cross-Linker With Ion-Pair Design for Tough Zwitterionic Hydrogel

Hydrogels have been widely used in various biomedical applications based on their ability to provide 3D frames with tissue-like elasticity and high water content. However, the role of the cross-linking agents in the hydrogels was undervalued in terms of biocompatibility, mechanical properties, degradability, and hydration of gels. In this study, an innovative zwitterionic dimethacrylate 2-[2-{2-(Methacryloyloxy)ethyldimethylammonium}ethyl-phosphate]ethyl disulfide (MPCSS) for the development of biodegradable and biocompatible hydrogels with entirely bio-inspired PC structure is reported. The MPCSS cross-linker includes the zwitterionic group providing nonfouling properties and a disulfide bond that can be degraded by reducing agents and enzymes. Moreover, MPCSS has an opposite arrangement of charged groups to that in the 2-methacryloyloxyethyl phosphorylcholine (MPC) monomer. The hydrogels developed from MPCSS and MPC allow the stronger mechanical properties upon electrostatic interaction between the oppositely charged groups and the higher water content than the MPC gels with the conventional cross-linker. The biocompatibility and fouling characteristics of MPC/MPCSS hydrogels are systematically investigated. Moreover, the degradation of MPCSS cross-linked hydrogels is evaluated through their weight loss and rheological data. Ultimately, MPC/MPCSS hydrogel is demonstrated to in situ encapsulate NIH-3T3 fibroblasts and provide an excellent 3D environment, facilitating cell remodeling and growth as a tissue scaffold.