Improvement of antibacterial, anti-inflammatory, and osteogenic properties of OGP loaded Co-MOF coating on titanium implants for advanced osseointegration

Abstract

The bacterial infection, especially for methicillin-resistant Staphylococcus aureus (MRSA), and the associated severe inflammatory response could extremely limit the crosstalk of RAW264.7 cells and mesenchymal stem cells (MSCs) and lead to the undesirable osseointegration of peri‑implants. It is highly demanded to modify the surface of titanium (Ti) implant to improve its anti-bacterial and anti-inflammatory properties and facilitate its disabled osseointegration. Herein, in our study, a multifunctional coating of zeolitic imidazolate frameworks-67 encapsulated osteogenic growth peptide (OGP) (ZO) was fabricated on titanium dioxide nanotubes (TNT) substrates (TNT-ZO) via the electrophoresis deposition (EPD) approach. The TNT-ZO substrates exhibited excellent antibacterial activity indicated by the reactive oxygen species (ROS) generation, outer membrane (OM) and inner membrane (IM) permeabilization change, adenosine triphosphate (ATP) decrease, and intracellular compounds (DNA/RNA) leakage. Importantly, the regulation effects of TNT-ZO coating modified titanium substrates on the RAW264.7-MSCs crosstalk could induce the anti-inflammatory and osteogenic microenvironment via multiple paracrine signaling of Runx2, BMP2, VEGF, and TGF-β1. The promoted effects of coating structure were investigated in vivo, including antibacterial effect, osteogenic differentiation of mesenchymal stem cells, and anti-inflammation of RAW264.7 cells, as well as infected bone regeneration and repair in bone defect transplantation model. The results demonstrated that MRSA was effectively eliminated by the hydrolysis of ZIF-67 nanoparticles on TNT-ZO substrates. Furthermore, the excellent osseointegration of peri‑implants was realized simultaneously by modulating the crosstalk of RAW264.7-MSCs. This study could provide a novel approach to designing a multifunctional coating on the Ti implants for infected bone regeneration in orthopedic applications.