Microbial-enabled materials for chronic wound niche engineering: From therapeutic states to adaptive control

Chronic wounds persist within a dysregulated niche in which infection, inflammation, oxidative stress, hypoxia, proteolytic imbalance, metabolic abnormalities, and defective tissue regeneration reinforce one another. Microbial-enabled materials are emerging as a distinct therapeutic platform because microorganisms and microbial-derived products can provide functions that conventional payloads cannot readily reproduce, including sustained biosynthesis, environmental responsiveness, metabolic conversion, and pathogen-dependent amplification. Yet these same properties also introduce variability in dose, persistence, spatial distribution, and safety. The central challenge is to control microbial activity within wound dressings. Here, microbial-enabled wound therapeutics are organized according to biological state, ranging from metabolically active probiotics and photosynthetic microorganisms to cooperative consortia, inactivated microbial preparations, membrane/extracellular vesicles, and host-dependent phages. This classification highlights distinct modes of biological activity and functional dependence that inform state-specific material-control requirements. The microbe-material-host interface governs confinement, molecular exchange, therapeutic flux, pathology-responsive activation, local deployment, and treatment termination. Therapeutic output is assessed over time alongside initial microbial loading. Translational readiness is then examined in terms of disease-relevant validation, biocontainment, potency control, manufacturing, storage, regulatory classification, and clinical workflow. The Review also examines sensing, feedback regulation, self-powered systems, and digital decision support for state-dependent wound therapy. Biomaterial interfaces can help make microbial therapeutic functions reproducible, risk-bounded, and clinically manageable.