BaTiO3 Doping Enhances Ultrasound-Driven Piezoelectric Bactericidal Effects of Fibrous Poly(L-Lactic Acid) Dressings to Accelerate Septic Wound Healing.

Abstract

Bacterial invasion in infected skin wounds triggers inflammation and impedes healing. Current therapeutic strategies incorporating drug interventions within wound dressings often result in drug resistance and delayed healing. Here, we developed a comprehensive therapeutic modality integrating piezoelectric fibrous dressing with controlled ultrasound stimulation for efficient healing in an infected wound model. The electrospun fibrous dressings composed of barium titanate (BaTiO3) doped poly(L-lactic acid) (PLLA) possess improved piezoelectric properties due to the aligned structure and high crystallinity, which achieved superior bactericidal efficacy upon ultrasound-mechanical-electric conversion that results in the production of reactive oxygen species (ROS). There were 88.72% and 90.43% killing rates of Staphylococcus aureus and Escherichia coli respectively upon ultrasound stimulation without any need for exogenous drugs, and a wound closure rate of 95.5% within 10 days. The in vivo results confirmed that this dressing effectively shortened wound closure time by about 2 days, with a much-improved healing rate of 14% compared with previously reported therapeutic strategies. This was accompanied by reduced inflammation and increased re-epithelialization and angiogenesis. Hence, our synergistic treatment by piezoelectric materials and controlled ultrasound stimulation provides a drug-free alternative approach in regenerative tissue engineering for simultaneously enhancing antibacterial effects and promoting wound healing.