Self‐Aggregation‐Induced Polymerization for Constructing Multifunctional Dynamic Zwitterionic Hydrogels

Zwitterionic hydrogels have attracted considerable attention as advanced biomaterials. However, the fabrication of traditional zwitterionic hydrogels typically relies on harsh polymerization conditions, and their backbone structures are non‐biodegradable. In this study, we develop a self‐aggregation‐induced polymerization (SAIP) mechanism that enables the spontaneous formation of multifunctional zwitterionic hydrogels under mild aqueous conditions, utilizing a rationally designed lipoic acid‐carboxybetaine monomer with lipoic acid‐modified hyaluronic acid (LAHA) crosslinker. This SAIP mechanism is driven by the synergistic interaction between the strongly hydrophilic zwitterionic moieties and hydrophobic 1,2‐dithiolanes, promoting monomer self‐aggregation into high‐concentration reactive microenvironments, thus facilitating efficient ring‐opening polymerization without external catalysts or stimuli. The incorporation of LAHA as a crosslinker results in the formation of a stable zwitterionic hydrogel, distinguished by its mild preparation conditions, rapid spontaneous gelation (116 s), and controlled depolymerization through dynamic disulfide bonds. Furthermore, the resulting hydrogel demonstrates high water content (>76%), robust mechanical properties (compressive stress up to 3.86 MPa), exceptional antioxidant activity (>90% DPPH scavenging), high biocompatibility, and superior living cell encapsulation and protection. This study provides a fundamental understanding of hydrogel formation through the SAIP mechanism and advances the development of zwitterionic hydrogels, making the resulting hydrogel an attractive candidate for biomedical applications.