Self-assembled Cu-alendronate nanoneedle sonozymes promoting infected bone regeneration via synergistic sonodynamic...

The high-efficiency treatment of infected bone defects necessitates the concurrent antibacterial and osteogenic activities of biocompatible scaffold materials. However, traditional clinical treatment modalities frequently suffer from antibiotic resistance, stubborn biofilm formation, and insufficient bone differentiation activity. Herein, we present a self-assembly strategy based on the coordination between Cu ions and Alendronate (ALN) to boost both antibacterial and osteogenic activities for the repair of infected bone defects. The self-assembly of ALN into a carrier-free drug delivery system can be induced by Cu ions, not only endowing ALN with excellent sonodynamic and chemodynamic activities for high-efficiency antibacterial therapy but also resulting in improved bioavailability and avoiding the possible carrier dilemma of low loading efficiency and poor stability. Moreover, Cu/ALN nanoneedles can selectively release Cu⁺, Cu²⁺, and ALN in bacterial microenvironment (BME) by breaking the Cu-N/Cu-O coordination bond under acidic conditions. The presence of Cu²⁺ in Cu/ALN provides effective glutathione peroxidase (GSH-px)-mimic catalytic activity for depleting glutathione (GSH) in BME, thereby avoiding the consumption of chemodynamic therapy (CDT)-generated reactive oxygen species (ROS) and achieving cascade amplification of ROS generation. Finally, the injectable Cu/ALN/GelMA hydrogels are fabricated through a single-step photochemical crosslinking process to examine the in vivo antibacterial efficacy and bone-regenerative potential of Cu/ALN. As a result, Cu/ALN-incorporated Gelatin Methacryloyl (GelMA) hydrogels significantly promote the healing of infected bone defects after implanting for one month through the ALN-facilitated osteogenic differentiation and Cu-ion-mediated cascade amplification of antibacterial activity. Overall, this work presents a novel perspective on the self-assembly multifunctional nanoplatforms with concurrent antibacterial and osteogenic activities for the treatment of infected bone defects.