Anion-π Interaction-Triggered Self-Healing Zwitterionic Hydrogel as an Immunocompatible Platform for Injectable Therapies.

Zwitterionic hydrogels have attracted considerable attention for protein stabilization, cell encapsulation, and therapeutic delivery owing to their highly hydrated and bioinert nature. Nevertheless, developing injectable zwitterionic hydrogels that can form under mild and cytocompatible conditions remains a major challenge, especially for the delivery of fragile proteins and living cells. This challenge mainly stems from the weak intrinsic intermolecular interactions and limited reactive groups of zwitterionic polymers, which make it difficult to establish stable hydrogel networks without additional molecular modification or external crosslinking. Here, we report an injectable zwitterionic supramacromolecular hydrogel (SSH) formed by the spontaneous assembly of poly(methacryloyloxyethyl sulfobetaine) (PSBMA) and poly(styrenesulfonate) (PSSNa). Molecular dynamics simulations support the involvement of anion-π interactions in gelation, leading to a self-healing physically crosslinked network. SSH exhibits injectability, self-healing behavior, intrinsic antiadhesive properties, and favorable immunocompatibility. The mild gelation process enables efficient cell encapsulation and injection while maintaining high cell viability. In addition, SSH stabilizes and delivers basic fibroblast growth factor (bFGF), resulting in improved therapeutic efficacy in a diabetic wound-healing model. This work establishes a mild gelation strategy for injectable zwitterionic hydrogels and highlights their potential in biomedical delivery and cell-based therapies.