Injectable zwitterionic hydrogels for biomedical applications: design strategies and emerging trends

Zwitterionic hydrogels have been extensively utilized in the biomedical field owing to their biocompatibility and immunocompatibility. The zwitterionic polymers that constitute these hydrogels possess electrically neutral yet highly polar structures, which facilitate the formation of a stable hydration layer via ionic solvation. This robust hydration layer imparts effective antifouling properties and low immunogenicity, making zwitterionic hydrogels highly suitable for in vivo applications, particularly in tissue repairing and drug/cell delivery applications. Conventional zwitterionic hydrogels typically require invasive surgical implantation and often exhibit poor integration with surrounding tissues. Injectable zwitterionic hydrogels (IZHs) have demonstrated advantages in overcoming these limitations, but their design remains challenging. This review outlines the structural features, design strategies, and biomedical applications of IZHs. Current challenges and future directions are also discussed to advance the clinical translation of this next-generation hydrogel platform. STATEMENT OF SIGNIFICANCE: This Review provides a systematic overview of injectable zwitterionic hydrogels (IZHs), focusing on their design principles, material properties, and potential biomedical applications. Unlike previous reviews on non-injectable hydrogels, it concentrates on IZHs, a rapidly emerging class of biomaterials that combine the intrinsic advantages of zwitterionic polymers-low immunogenicity, good biocompatibility, and antifouling performance-with features such as in situ gelation, conformal integration with irregular tissues, and minimally invasive delivery. By connecting fundamental polymer design to practical biomedical applications, this Review addresses a gap in the literature and highlights the translational potential of IZHs for both research and clinical use.