Energy reconversion of ultrasound on a piezoelectric hydrogel promotes ROS/CO generation and wound self-closure for infected chronic wound healing

This work developed a de novo sonosensitizer based on carnosine_zinc piezoelectric metal-organic frameworks (PMOFs) that possesses a prominent reactive oxygen species (ROS)-generating function, biocompatibility, and degradability. Further, the PMOF was modified by a carbon monoxide (CO) donor through a metal complexation reaction to result in a multifunctional CO-PMOF to launch CO/ROS-mediated antimicrobial under ultrasound (US). However, the heat generated during sonodynamic therapy (SDT) may harm wounds. To minimize the waste energy and promote wound self-closure rate, a strong adhesive, and rapid thermal-responsive contraction (52.4%, 4 min), injectable hydrogel was designed to load CO-PMOF. The resulting ultrasonic triple-responsive hydrogel (UTGel) exhibits an effective biofilm destruction capability based on a CO/ROS-mediated antimicrobial therapy. After administration in an infected diabetic skin wound model in mice, UTGel can efficiently harvest the thermal energy by the CO-PMOF under US to trigger a centripetal shrinkage of the hydrogel and guide rapid wound self-closure.