Construction of a Ti implant-based responsive OPG release platform for enhanced osteoporotic bone regeneration <i>via</i> programmed regulation of osteogenesis and bone resorption

The potential for persistent and controllable delivery of osteoprotegerin (OPG) under osteoporotic conditions has become an essential property of bone implants to promote osseointegration and osteogenesis. Herein, a microenvironment-responsive surface coating for titanium (Ti) implants by immobilizing metal-organic frameworks (MOFs) loaded with OPG onto alkali heat-treated Ti surfaces <i>via</i> gelatin (Gel) (AHT-MOF@OPG-GEL) was successfully fabricated. In a weakly acidic environment, MOF@OPG can achieve responsive degradation and slow release of zinc ions (Zn²⁺) and OPG, which not only inhibits osteoclast activity and osteoclastic biomarker expressions but also potentiates osteoblast proliferation and differentiation <i>in vitro</i>. Moreover, alkali heat treatment was favorable for the hydrophilicity and cell adhesion of the Ti surface. In addition, <i>in vivo</i> experiments in the osteoporotic bone defect model confirmed that the MOF-based functional coating could promote the generation of new bone around the implant, thereby enhancing the bonding strength between the implant and the surrounding bone tissue and effectively facilitating the osseointegration of the implant with the bone tissue. In conclusion, this study is expected to provide new ideas for improving the osseointegration of implants under osteoporotic conditions.