Conductive Microneedles Loaded With Polyphenol‐Engineered Exosomes Reshape Diabetic Neurovascular Niches for Chronic Wound Healing

Abstract

Diabetic wound healing remains a major clinical challenge due to the accumulation of advanced glycation end products (AGEs), reactive oxygen species (ROS), and proinflammatory cytokines under hyperglycemic conditions, which collectively impair neurovascular regeneration. Here, a biological-electrical therapeutic platform is reported by synergizing polyphenol-engineered Saccharina japonica exosomes (CA@Exos)-derived biological signals with electroconductive microneedles (pCNTs-ASA MNs)-delivered electrical cues, achieving a dual-pathway to reshape neurovascular niches during the diabetic wound healing process. CA@Exos serve as bioactive cargo to suppress AGE formation, scavenge ROS, and reverse the inflammatory microenvironment, while their intrinsic bioactivities in modulating angiogenesis and neurotrophic signaling enhanced Schwann cell-vascular endothelial cell crosstalk. Concurrently, the conductive pCNTs-ASA MNs functioned as spatiotemporal bioelectric scaffolds, enhancing exosome uptake and amplifying endogenous wound currents by transmitting exogenous electrical stimulation. This dual-modality strategy synergistically promotes angiogenesis, neural regeneration, and re-epithelialization, achieving full-thickness wound closure in diabetic rats. This work pioneers the therapeutic potential of plant-derived exosomes with conductive MNs-mediated biophysical stimulation, offering a promising therapeutic strategy to disrupt the pathological feedback loop of hyperglycemic microenvironment for diabetic wound healing. The combined strategy, supported by a favorable biosafety profile and high adaptability, demonstrates a bright prospect for clinical translation, offering new hope for patients with chronic diabetic wounds.