Ultrasound-Responsive Microneedles Eradicate Deep-Layered Wound Biofilm Based on TiO₂ Crystal Phase Engineering

Wound biofilm infection has an inherent resistance to antibiotics, requiring physical debridement combined with chemical reagents or antibiotics in clinical treatment, but it is invasive and may exist as incomplete debridement. So, a new type of noninvasive and efficient treatment is needed to address this problem. Here, the crystal phase engineering of TiO₂ is presented to explore the sonocatalytic properties of TiO₂ nanoparticles with different phases, and find that the anatase-brookite TiO₂  (AB) has the best antibacterial efficiency of 99.94% against S. aureus under 15 min of ultrasound (US) irradiation. The type II homojunction of AB not only enhances the adsorption and decreases the activation energy of O₂ , respectively, but also has a great interfacial charge transfer efficiency under US, which can produce more reactive oxygen species than other types of TiO₂ . The microneedles (MN) penetrate the biofilm in wound tissue and quickly disperse the loaded AB into the biofilm because the ultrasonic cavitation accelerates the dissolution of microneedles, which non-invasively and efficiently eradicates the deep-layered biofilm under US. This work explores the relationship between the phase composition of TiO₂ and sonocatalytic property for the first time, and provides a new treatment strategy for wound biofilm infection through US-assisted microneedles therapy.