Double Bionic Deformable DNA Hydrogel Microneedles Loaded with Extracellular Vesicles to Guide Tissue Regeneration of Diabetes Ulcer Wound

Abstract Due to the high blood glucose and low oxygen environment in diabetes wounds, complex pathological problems arise, such as failure to upregulate healing factors, biological barriers generation, microvascular lesions, and skin neuropathy. Inspired by nature and traditional Chinese paper‐cutting technology, polypeptide deoxyribonucleic acid (DNA) hydrogel microneedles (MNs) (P‐DNA gel MNs) are prepared. The obtained P‐DNA gel MNs possess optimized structure and large deformability, providing excellent clamping, stability, skin penetration, large deformation, tissue adhesion, and antibacterial properties. By incorporating extracellular vesicles (EVs) extracted under hypoxia (H‐EVs‐hypoxia), P‐DNA gel MNs can regulate tissue microenvironment, scavenge free radicals, and reduce inflammation. Notably, P‐DNA gel MNs integration system activates immune regulation and beneficial pathways, promoting neurogenesis and angiogenesis, reducing pathological pain, and achieving high‐quality healing. Overall, P‐DNA gel MNs system presents a fundamental mechanism for clinical transformation in treating diabetes wounds.