Adaptive Intelligent Microneedles for Sustained Wound Healing: Translating Microenvironment Signals into Stage-Specific Therapeutic Responses.

Background: Chronic wounds are a complex of interconnected issues, including biofilm-associated infection, persistent inflammation, oxidative stress, altered pH, metabolic dysfunction, proteolytic imbalance, hypoxia, vascular impairment and poor tissue regeneration. These anomalies encourage endogenous activation of smart microneedles (MNs) and prevent healing. MNs can transition from passive local medication delivery to adaptive therapy, which adjusts to the biological changes in chronic wounds. Methods: This review introduces an adaptive wound-interface framework to evaluate smart MN strategies for chronic wound healing. A pathology-driven approach links wound-associated cues to responsive materials, activation mechanisms, therapeutic functions, healing stages, and translational requirements. It examines ROS-, pH-, glucose-, enzyme-, bacteria-, and hypoxia-responsive systems; advanced MN architectures; and their integration with infection control, immunomodulation, vascular restoration, tissue regeneration, and stage-specific therapy. Results: The evidence shows a clear progression from simple drug-loaded MNs to systems in which pathological signals actively tune material degradation, catalytic activity, therapeutic release, or sequential therapy. Biofilm, chronic inflammation, vascular dysfunction, and impaired regeneration are common therapeutic targets. Endogenous triggers could be ROS, pH, glucose, and disease-related enzymes. Antibiofilm therapy, redox normalization, immune reprogramming, oxygen regulation, angiogenesis, re-epithelialization, extracellular matrix remodeling, and scar control are increasingly coordinated by compartmentalized or sequential architectures and responsive chemistries in advanced platforms. Clinically relevant activation thresholds, stimulus-response reproducibility, polymicrobial biofilms, irregular wound mechanics, sterilization, nanomaterial stability and safety, manufacturing scale-up, and regulatory translation are major challenges as functional complexity increases. Conclusion: Smart MNs are evolving from localized drug-delivery devices to physiologically educated therapeutic interfaces that may manage therapy time, location, and manner using the chronic wound microenvironment. Not the most responsive components, clinically viable systems will feature biologically meaningful sensing, temporally appropriate therapy, repeatable fabrication, and demonstrable benefit over current wound care. Instead of wound closure, future development should include clinically established stimulus ranges, stage-adaptive therapeutic programming, translationally practical designs, and enduring functional tissue restoration.