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

This study establishes a bio‐electroceutical interface by synergizing engineered exosome‐derived biological signals with electroconductive microneedle‐delivered electrical cues, achieving dual‐pathway reprogramming of the diabetic neurovascular niches and accelerating 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. This study establishes a bio-electroceutical interface by synergizing engineered exosome-derived biological signals with electroconductive microneedle-delivered electrical cues, achieving dual-pathway reprogramming of the diabetic neurovascular niches and accelerating 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. Advanced Science, Volume 12, Issue 43, November 20, 2025.