ECM-Mimetic Biomineralized Ti Implant Coating Mediates Quiescence of Osteoclast Precursor Cells to Restore Osteogenesis-Angiogenesis Coupling for Accelerating Osteoporotic Fracture Repair.

Titanium (Ti) implants are widely used for treating bone fractures, but their clinical success is often limited by high failure rates due to the excessive osteoclastogenic activation of osteoclast precursor cells (OPCs) at the implantation site, particularly in patients with osteoporosis. Notably, the excessive osteoclastic differentiation of OPCs potently disrupts the osteogenesis-angiogenesis coupling to promote osteoclast-mediated osteolysis while dismantling the pro-osteogenic type H vascular niches, resulting in elevated risk of implant destabilization. To address this issue, here we report a biomineralization-tuned extracellular matrix (ECM)-mimetic biomineralized coating (TCC@Har-CaG) to enable redox rewiring of OPCs for promoting new bone formation. Specifically, we employed collagen-I as the substrate material to fabricate the stimuli-responsive biomineralized coating for the cooperative delivery of antioxidative gallic acid (GA) and osteoclast precursor cell inhibitor Harmine. The TCC@Har-CaG coating could sustainably release GA after implantation to effectively relieve reactive oxygen species (ROS) stress at the osteoporotic bone defects, which could synergize with Harmine to efficiently induce OPC quiescence and restore osteogenesis-angiogenesis coupling, thus cooperatively promoting new bone generation. This study presents a potential tactic for addressing osteoporotic bone fractures in clinical settings.