LAUSR

Zwitterionic hydrogels with exceptional antifouling properties and biocompatibility have gained widespread attention in biomedical applications. However, achieving robust mechanical performance while maintaining high water content within a single‐network zwitterionic hydrogel remains challenging. Traditional covalent crosslinking strategies often lead to brittleness and irreversible damage. Herein, a novel acylsemicarbazide‐containing carboxybetaine methacrylate (ACBMA) monomer is designed and synthesized that enables the construction of a pure zwitterionic poly(ACBMA) (pACBMA) hydrogel without chemical crosslinkers. The pACBMA hydrogel exhibits high water content exceeding 95% and superior mechanical properties, including compressive fracture stress of 3.92 MPa, compressive strain up to 99% without breaking, and toughness of 212 ± 2.4 kJ m−3, outperforming chemically crosslinked poly(carboxybetaine methacrylate) (pCBMA) hydrogel. Additionally, the pACBMA hydrogel exhibits excellent injectability, moldability, and even recyclability through the preparation of microgels. Through the unique molecular design, the pACBMA hydrogel integrates multiple non‐covalent interactions, including hydrogen bonding, electrostatic interactions, polymer chain entanglement, and steric hindrance of the α‐methyl group. These interactions synergistically contribute to the combination of high hydration, mechanical robustness, and dynamic tunability. These results provide a new design strategy for constructing high‐performance zwitterionic hydrogels with promising potential for diverse biomedical applications.