Osteoimmunomodulatory properties of a magnesium-doped phase-transited lysozyme coating on titanium

Abstract

The inflammation aroused by implants is the main cause of implant failure. Therefore, the design paradigm of implants has changed from “inertia” to “immunomodulatory”. Although multiple bioactive ions exert effects on osteogenesis, how magnesium ions (Mg2+) manipulate immune response via inducing macrophage polarization and subsequently promote osteogenesis needs further investigation. In this study, phase-transited lysozyme (PTL) is deposited onto the surface of titanium (Ti) to construct a functional coating and magnesium chloride solution at 2.5 mM, 5 mM and 10 mM was utilized to produce PTL coatings with different concentrations of Mg2+ (PTL-Mg2.5, PTL-Mg5 and PTL-Mg10). The characterization of the magnesium-doped PTL coatings (PTL-Mg) was tested by scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX) and inductively coupled plasma atomic emission spectroscopy (ICP-AES). In addition, we utilized a co-culture system of macrophages and rat bone merrow mesenchymal stem cells (BMSCs) to investigate the osteoimmunomodulatory effects of PTL-Mg coatings. The results showed that compared with other groups, PTL-Mg5 group can create a favorable osteoimmune microenvironment by regulating macrophages polarization and release of inflammatory cytokines, then promote adhesion, proliferation and osteogenic differentiation of BMSCs. The in vivo results further verified the most excellent osteointegration ability of PTL-Mg5 in rat femur lateral condyle defects. This work indicates a promising way for design paradigm of implants with immunomodulatory properties by inducing PTL-Mg5 coating on Ti, providing a new strategy for implants surface modification.