Living Hydrogels: Harnessing Microorganism-Material Synergy for Next-Generation Therapeutics

Microorganism-based therapies, particularly those utilizing probiotics, have emerged as a powerful biomedical strategy owing to their inherent living functionalities. These living systems can dynamically interact with host environments and self-regulate their activity, offering superior adaptability, prolonged functionality, and microenvironmental responsiveness compared to conventional non-living therapeutic platforms. Despite these advantages, the direct administration of probiotics faces several challenges, such as poor viability, limited retention at target sites, and the inability to control therapeutic effects in a spatiotemporally precise manner. To address these challenges, embedding probiotics within hydrogel matrices has proven effective in enhancing microbial stability, prolonging in vivo retention, and enabling precise and sustained therapeutic delivery through synergistic interactions between the hydrogels and living microorganisms. This review provides a comprehensive overview of the materials and design strategies employed in the construction of living microorganism-encapsulated hydrogels (living hydrogels), with particular emphasis on the dynamic interactions and synergistic mechanisms of hydrogel-microorganism systems. We further illustrate how these mechanisms can achieve various biomedical applications, such as modulating gut microbiota to treat gastrointestinal disease and accelerate wound healing, or leveraging microbial-induced immune regulation for effective cancer therapy. Finally, the current challenges and future directions associated with the clinical translation of living hydrogels are highlighted. Therefore, the unique multifunctionality and therapeutic promise of living hydrogels position them as compelling candidates for the development of next-generation biomaterials with unprecedented therapeutic potential.