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.