An ultrasound-responsive hydrogel with piezoelectric-enhanced electrokinetic effect accelerates neurovascular regeneration for diabetic wound healing

Abstract

Diabetic wound healing is hindered by the critical effects of poor local vascularization, peripheral neuropathy, and bacterial infection, which remains a formidable challenge. Available wound dressings suffer from limited therapeutic efficacy owing to the inadequate addressing of neurovascular lesions. Herein, an ultrasound-responsive composite hydrogel composed of a gelatin/polyvinyl alcohol (PVA) interpenetrating polymer network doped with piezoelectric (K,Na)NbO₃ (KNN) nanocrystals and reduced graphene oxide was rationally designed to realize sonoelectric conversion to accelerate diabetic wound healing by facilitating local neurovascular regeneration. The composite hydrogels present exceptional self-healing, skin-adhesive, and conductive properties. More encouragingly, this hydrogel is endowed with excellent sonoelectric conversion performance by piezoelectric-enhanced electrokinetic effect under ultrasound irradiation. The results in vitro and in vivo demonstrate that the composite hydrogel combined with ultrasound irradiation can enhance the angiogenesis of endothelial cells, upregulate the neurotrophic effects of Schwann cells to support neurite growth, and inhibit bacterial activities, resulting in significant local angiogenesis and nerve regeneration in diabetic wounds. This strategy offers an efficacious approach and leads the development of electroactive biomaterials for diabetic wound treatment.