Exosome-Biomaterial Platforms for Diabetic Skin Infections: Microenvironment Remodeling, Responsive Delivery, and Clinical Translation.

Diabetic skin infections, particularly diabetic foot ulcers (DFU), remain difficult to treat because infection, biofilm formation, persistent inflammation, oxidative stress, hypoxia, impaired angiogenesis, and extracellular matrix (ECM) disruption coexist within a hostile wound microenvironment. Conventional treatments, including antibiotics, surgical debridement, negative pressure wound therapy, and standard dressings, are indispensable but often fail to simultaneously suppress infection and restore regenerative healing. Exosomes have emerged as promising acellular mediators for diabetic wound repair because they can coordinate immune regulation, angiogenesis, matrix remodeling, and re-epithelialization. However, direct exosome administration is limited by rapid clearance, poor local retention, dilution by wound exudate, dose inconsistency, and manufacturing heterogeneity. Biomaterial platforms, including hydrogels, microneedle patches, membranes, cryogels, porous scaffolds, and responsive nanocomposite systems, provide a rational strategy to protect exosome bioactivity, prolong local retention, and enable sustained or stimulus-responsive release. More importantly, these materials can be engineered to actively regulate infection-associated pathological barriers, including biofilm persistence, excessive oxidative stress, hypoxia, and impaired tissue reconstruction. This review summarizes recent advances in exosome-biomaterial systems for diabetic skin infections, with emphasis on delivery design, microenvironment-responsive release, anti-infective and regenerative mechanisms, platform comparison, and clinical translation. We further discuss key translational challenges, including exosome source selection, dose standardization, potency assays, scalable manufacturing, storage stability, biosafety, regulatory classification, and clinical trial design. Current evidence suggests that exosome-biomaterial systems can improve wound closure, vascularization, collagen deposition, re-epithelialization, and infection control in preclinical models. Nevertheless, high-quality clinical evidence remains limited. Future studies should prioritize clinically relevant infected diabetic wound models, standardized quality-control frameworks, and simplified delivery systems compatible with routine wound care.