Probiotic-hydrogel systems for microbiome-associated diseases: design principles, preclinical evidence, and translational challenges

The human microbiome provides a robust ecosystem for mucosal barrier function, immune regulation, metabolism, and resistance to pathogen infection. Dysbiosis causes inflammatory bowel disease, oral inflammation, wound damage, skin disease, and cancer-related immune dysregulation. Current probiotic therapy is limited by low survival during storage and administration, low oral bioavailability, short retention time, and insufficient targeting. Probiotic-hydrogel systems combine viable microorganisms with natural or synthetic polymer networks to promote probiotic protection, local retention, and controlled release. They can also incorporate prebiotics, engineered bacteria, oxygen-releasing agents, antioxidants, growth factors, drugs, or advanced manufacturing techniques such as microfluidics and 3D printing. Recent preclinical studies suggest that probiotic-hydrogel can modulate local microbes, suppress pathogens, control inflammation, support barrier repair, and promote tissue regeneration. However, most evidence is far from clinical, and human data are limited to a small number of oral and periodontal applications. In this review, we summarize the design strategies, encapsulation approaches, mechanistic frameworks, disease-based evidence, and translational challenges of probiotic-hydrogel. In particular, we paid attention to evidence level, safety, manufacturing, regulatory classification, product stability, clinical trial design. Such issues need to be well understood before probiotic-hydrogel can move from experimental platforms to clinically applicable microbiome treatments.