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MicroRNA-493-5p engineered exosomes delivered via piezoelectric microneedles for epigenetic modulation of macrophages in diabetic wound healing - PubMed

6 hours ago
  • #exosome therapy
  • #diabetic wound healing
  • #epigenetic modulation
  • Diabetic foot ulcers are a global issue with impaired healing due to dysregulated macrophage polarization.
  • A novel exosome-based delivery platform combines miR-493-5p-engineered M2 macrophage exosomes with piezoelectric GelMA microneedles for diabetic wound healing.
  • Engineered EXO@miR-493-5p are embedded in GelMA microneedles and delivered via a ZnO piezoelectric substrate with nanosilver/GOx coating for antibacterial and antioxidant benefits.
  • Ultrasound-induced electrostimulation enhances exosome deposition and endocytic uptake, enabling sustained, localized cargo release.
  • miR-493-5p targets HDAC1 to amplify histone H3K18 lactylation, activating the STAT6 axis and driving metabolic reprogramming toward M2 polarization.
  • In vitro, EXO@miR-493-5p promote M2 markers and angiogenesis.
  • In vivo, they accelerate wound closure, promote re-epithelialization, collagen deposition, and neovascularization while reducing ROS and inflammation.
  • The platform offers a translatable, epigenetic-metabolic strategy for chronic diabetic wounds.