Hydrogel-Based Microneedles for Diabetic Wound Repair: Translational Requirements for Diabetic Foot Ulcer Therapy

Diabetic foot ulcers (DFUs) arise from interacting neuropathic, biomechanical, vascular, and infectious processes that are incompletely reproduced by experimental diabetic wound models. Hydrogel-based microneedles (HBMNs) offer opportunities for localized therapeutic delivery, but their clinical value depends on whether tissue penetration provides advantages over appropriately formulated topical treatments. This critical narrative review examines HBMN architectures, therapeutic strategies, and barriers to clinical translation in DFU management. HBMN systems are distinguished by their hydration-dependent behavior, with direct therapeutic evidence limited to microneedle platforms containing a functional hydrogel component. Preclinical studies have explored approaches targeting infection and biofilms, persistent inflammation, oxidative stress, impaired oxygenation, and defective tissue regeneration. Recent developments include polymicrobial biofilm targeting, metabolic modulation, and extracellular-vesicle delivery. Preset release, stimulus-responsive delivery, and emerging feedback-informed approaches are discussed in relation to their distinct capabilities and limitations. Despite promising experimental findings, important uncertainties remain regarding the intended wound interface, delivered dose, cargo stability and potency, compatibility with offloading, and safety in ischemic or infected tissue. We propose a staged translational framework linking intended clinical indications to relevant disease models, appropriate comparators, reproducible product quality, and patient-important outcomes. HBMNs should be developed as adjuncts to multidisciplinary DFU care, with priority given to demonstrating clinically meaningful advantages over simpler delivery systems rather than increasing the functional complexity of experimental prototypes.