Decoration of Porous TiO₂ Implants With Metal-Organic Composites Enables Synergistic Therapy for Osteoporotic Fracture Healing.

Abstract

Osteoporotic fracture healing is trapped in a vicious cycle where multiple pathological factors, including persistent oxidative stress, inadequate vascular supply, and an imbalance bone remodeling process that favors resorption, combine to form a hostile niche for regeneration. The intricate interaction of these pathologies highlights the need to transform titanium implants from inert devices into active platforms for bone regeneration. In this study, a multifunctional coating where titanium dioxide nanotubes (TNT) are decorated with metal-organic networks (TNT@EZCA) is developed for coordinated regulation of pathological processes. The metal-organic network, composed of EGCG, Zn² ⁺, Ca² ⁺, and ALN, is engineered to orchestrate a pro-regenerative microenvironment that concurrently targets oxidative stress, angiogenesis, and bone homeostasis. In vitro studies confirm that the coating effectively scavenges reactive oxygen species, promotes endothelial cell functions, and re-establishes the balance between osteoblast and osteoclast. In an osteoporotic fracture model, TNT@EZCA significantly accelerates bone regeneration, improves bone microstructure and callus vascularization, and exerts a systemic osteoprotective effect. This study demonstrates that a multifunctional and integrated regulatory strategy effectively drives a systemic osteoprotective effect involving vascular network reconstruction and bone homeostasis restoration, offering a potential therapeutic strategy for improving the healing of osteoporotic fractures.