Abstract

Several studies have shown that conductive particles can enhance the activity of piezoelectric materials, including their piezocatalytic behavior. To exploit this effect in biomedical applications, this study aims to develop and evaluate ultrasound-responsive 3D-printed piezocatalytic scaffolds by enhancing the piezoelectric activity of zinc oxide (ZnO) through conductive thermally reduced graphene oxide (TrGO). Hybrid ZnO/TrGO particles were synthesized and incorporated into a polycaprolactone (PCL) matrix to fabricate 3D-printed scaffolds. Piezocatalytic activity under ultrasound (US) stimulation was first evaluated in particle dispersions using methylene blue degradation. The piezoelectric response of the printed composites was assessed via voltage generation under US, while antibacterial performance against Escherichia coli and Staphylococcus aureus was investigated under static and US-stimulated conditions. Biocompatibility was evaluated using human umbilical cord-derived mesenchymal stem cells (uMSCs). Hybrid ZnO/TrGO particles exhibited significantly higher piezocatalytic activity under US compared to pure ZnO. When embedded into PCL, the hybrid fillers enabled voltage generation under US, reaching peak-to-peak outputs of 111 +/- 1 mV, attributed to synergistic coupling between piezoelectric charge generation and enhanced electron transport. The 3D-printed composites showed reduced bacterial adhesion compared to pure PCL, an effect further enhanced under US stimulation. In bacterial suspension, all materials were effective against E. coli under US, whereas only ternary PCL/ZnO/TrGO scaffolds significantly inhibited S. aureus, highlighting the role of TrGO. All scaffolds demonstrated excellent cytocompatibility, with enhanced uMSC proliferation at day 7 under US stimulation. These results demonstrate that TrGO amplifies ZnO piezocatalytic behavior, enabling the design of multifunctional ultrasound-activated scaffolds for antibacterial biomedical applications.