Single-Atom-Engineered Implant Materials with Lactate Dehydrogenase-Like Activity for Sustainable Bone Repair and Regeneration.

Abstract

Fractures represent a major clinical burden, frequently leading to substantial impairment and heightened risks of disability and mortality, but current fixation materials exhibit limited osteoinductive capacity. Lactate dehydrogenase (LDH) cooperates with NADH oxidase (NOX) to drive metabolic reprogramming that enhances osteogenic differentiation and regeneration. Herein, we developed a single-atom-engineered implant with superior LDH-like activity and sustainable bioactivity, which effectively promotes the transition from the reparative to remodeling phase during fracture healing in mouse and rabbit models. During the inflammatory phase, downregulation of CTX-1 suppresses bone resorption, whereas upregulation of Sox9 enhances chondrocyte conversion. In the subsequent repair phase, CTX-1 upregulation facilitates bone remodeling. After 5 weeks of implantation, the single-atom-engineered implant promotes calcium influx through the mechanosensitive Piezo1 channel, establishing a favorable redox microenvironment for osteogenesis. This new generation of single-atom-engineered implants presents a promising advance in fracture fixation by combining sustained biocatalytic function with enhanced bone regeneration.