Lotus leaf-inspired radially aligned PHBV dressing with herbal delivery and ultrasound-responsive piezoelectricity for infected diabetic wound healing

Abstract

Diabetic wounds are frequently complicated by persistent infection, excessive inflammation, and impaired tissue regeneration, which collectively hinder effective wound healing. Developing multifunctional dressings that simultaneously provide topographical guidance, infection control, and regenerative support therefore remains an important challenge. Lotus leaf-inspired radially aligned poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) nanofiber dressings were fabricated using a self-designed electrospinning device and loaded with Salvia miltiorrhiza Bunge-Radix Puerariae herbal compound (SRHC). The radial architecture guided cell migration from wound edges toward the center, while SRHC incorporation improved hydrophilicity and was associated with enhanced antimicrobial, anti-inflammatory, and hemostatic performance. PHBV dressings generated detectable ultrasound-responsive piezoelectric outputs, confirming their electromechanical activity. Under ultrasound activation, SRHC-loaded PHBV dressings enhanced cell proliferation and collagen-related gene expression. In a Staphylococcus aureus-infected diabetic wound model, the combined treatment achieved an antibacterial rate exceeding 99.9%, nearly complete wound closure by day 15, enhanced collagen deposition and increased hair follicle regeneration. Transcriptomic analysis revealed an integrated wound-tissue response involving keratinization and pathways related to IL-17, TNF, MAPK, PI3K-Akt, and fluid-shear-stress responses. These findings demonstrate the potential of integrating bio-inspired topographical guidance, local herbal compound delivery, and ultrasound-responsive electromechanical functionality within a single nanofibrous dressing for infected diabetic wound repair.