Polysaccharide-based live hydrogels for probiotic intestinal and wound therapy

Probiotics as therapeutic microorganisms have been widely used for gastrointestinal disorders and wound therapy. However, poor viability in wound and gastrointestinal environments limits their efficacy. Polysaccharide-based hydrogels are suitable delivery systems for probiotics to overcome these challenges. These hydrogels by benefiting from their biocompatibility, biodegradability, and non-toxicity can create suitable microenvironments for probiotics. Unlike passive traditional carriers (such as capsules or inert nanoparticles), these "live hydrogels" are dynamic carriers encapsulating viable cells as bioreactors for sustained metabolite production. This review systematically studies the design, fabrication, and application of such live hydrogels for intestinal and wound therapy. Intestinal therapy emphasizes ionic-crosslinking along with co-encapsulation with protective agents (such as prebiotics and antacids) to improve cell viability and pH-responsive release of cells to restore gut microbiota and combat infections. On the other hand, in wound management, the release of probiotics is prevented to avoid the immune responses. Instead, these live hydrogels act as bioreactors for sustained production of release of therapeutic metabolites. New approaches such as antioxidant coatings and genetic engineering can further improve the efficacy of probiotics. However, the long-term viability, biosafety, and clinical translation remain challenges that need to be addressed.