Ultrasound activated herbal bio-heterojunctions for self-catalytic regulation and bacterial cuproptosis-like death in the treatment of implant infection

Abstract Conventional antibiotic strategies often fail to consistently suppress escaping planktonic bacteria and even induce antibiotic resistance, allowing implant-associated infections (IAIs) to persist. In this study, we demonstrated an antibiotic-free coating engineered with an herbal bioheterojunction featuring a shell-in-shell structure where Cu 2 O forms the core, strontium (Sr) is loaded in the inner shell, and curcumin (Cur) is nucleated in situ at the outer heterointerface (Cu 2 O-Sr/Cur). Ultrasound-triggered reactive oxygen species (ROS) generation by the outer heterostructure (Cu 2 O/Cur), coupled with Cu(I)-induced cuproptosis-like bacterial death, achieved antibacterial rates of 99.56% against S. aureus and 99.43% against E. coli . When ultrasonication ceases, the released Cu(I) undergoes disproportionation reactions to form Cu(II), which can chelate with Cur to form Cu-Cur metal complexes. These complexes exhibit enhanced antioxidative properties through self-catalytic regulation, the scavenging of ROS, and the activation of anti-inflammatory M2 macrophage phenotype. Moreover, strontium release from the inner shell simultaneously suppressed osteoclast activity and promoted osteogenesis, resulting in trabecular number and thickness increases of 129.03% and 56.71%, respectively, compared with those in control group. Therefore, our work establishes a sequential treatment strategy for the antibacterial properties and osteointegration ability of IAIs.