Microgalvanic and Cuprotosis-like-Mediated Dual Engineered Metabolic Interference Strategy to Combat Implant-Associated Infections.

Abstract

Implant-associated infections have become a persistent threat affecting the success rate of clinical implant surgeries. Existing multitype antimicrobial films for implant surfaces still suffer from such problems as film detachment and erroneous killing of normal cells. Targeting the dual-core processes of the electron transport chain (ETC) and the tricarboxylic acid cycle (TCA) within bacterial energy metabolism networks, this work employs an engineered ion implantation method to sequentially inject copper ions and hydrogen ion onto the surface of the nickel-titanium alloy, developing a nondetachable, interface-free modified layer. Hydrogen ion implantation reduces exposed nickel oxide on the substrate to metallic nickel, forming a Cu-Ni microgalvanic system, which can continuously capture electrons from the bacterial membrane ETC, thereby inhibiting bacterial adenosine triphosphate synthesis. Furthermore, copper ions are intracellularly released via bacterial membrane ion channels, triggering a cuprotosis-like process. This process impairs bacterial metabolism, manifested as reduced iron uptake, diminished heme utilization capability, and inhibition of the TCA cycle. <i>In vivo</i> experiments validate its potent antibacterial effect in the infected subcutaneous tissue of a rat model. Moreover, the film can facilitate rapid surface endothelialization. This engineered dual-pathway interference strategy targeting bacterial energy metabolism provides the theoretical guidance for safely reducing the risk of implant infections.