Piezoelectric dual-network tough hydrogel with on-demand thermal contraction and sonopiezoelectric effect for promoting infected-joint-skin-wound healing via FAK and AKT signaling pathways

ABSTRACT The dynamic and whole stage management of infected wound healing throughout the entire repair process, including intelligent on-demand wound closure and the regulation of the transition from bactericidal to reparative phases, remains a major challenge. This study develops sonopiezoelectric-effect-mediated on-demand reactive-oxygen-species release by incorporating piezoelectric barium titanate modified with gold nanoparticles and a thermally responsive dual-network tough hydrogel dressing with a physical network structure based on ureidopyrimidinone-modified gelatin crosslinked by multiple hydrogen bonds, and with a chemical network structure based on N-isopropylacrylamide and methacryloyl gelatin formed via radical polymerization. This hydrogel exhibits temperature-sensitive softening, on-demand thermal contraction performance, high mechanical strength, good tissue adhesion, outstanding piezoelectricity, tunable sonopiezoelectric behavior, regulatable photothermal properties and desirable biocompatibility. The tunable sonopiezoelectric effect enables the hydrogel to eliminate wound bacteria in the short term, and effectively promote human fibroblast proliferation and migration over the long term. The hydrogel dressing actively contracts to close wound edges and further promotes the healing of MRSA-infected skin defects in the neck of mice by promoting fibroblast migration, enhancing collagen deposition and facilitating angiogenesis via up-regulating the FAK and AKT signaling pathways, providing a novel design strategy for developing dressings targeting chronic joint-skin wounds.