Osteoimmunomodulation mediating improved osteointegration by OGP-loaded cobalt-metal organic framework on titanium implants with antibacterial property

Bacterial infection and the resulting inflammation response not only affect the functions of osteogenic-relative cells but also lead to the failure of titanium (Ti)-based implantation. It is urgent to develop multifunctional (antimicrobial, anti-inflammation, and pre-osteogenesis) titanium implants to address this tissue. Herein, an osteogenic growth peptide (OGP) loaded zeolitic imidazolate frameworks-67 (ZIF-67) coating was fabricated on titanium dioxide nanotubes (TNTs) to prepare a TNT-ZIF-67@OGP surface. The ZIF-67@OGP coating was rapidly dissolved under an acidic environment with pH-sensitive property. Moreover, the TNT-ZIF-67@OGP displayed a strong antibacterial activity against Escherichia coli (E. coli), Staphylococcus aureus (S. aureus), Streptococcus mutans (S. mutans), and methicillin-resistant Staphylococcus aureus (MRSA) owing to the hydrolysis of ZIF-67 nanoparticles and the formation of an alkaline microenvironment. The implants had good biocompatibility toward mesenchymal stromal cells (MSCs) and macrophages. Notably, the TNT-ZIF-67@OGP could suppress the inflammatory response and simultaneously improve the cellular differentiation of MSCs under an inflammatory environment. In vivo study further revealed that TNT-ZIF-67@OGP implants presented strong antimicrobial and anti-inflammatory properties at the early stage of implantation, thereby enhancing the osteointegration of bone-implant at the late stage. Thus, this multifunctional Ti implant combining osteoimmunomodulatory and antibacterial effects is a promising candidate for implant-associated infectious bone regeneration.