Strontium-zinc phosphate chemical conversion coating improves the osseointegration of titanium implants by regulating macrophage polarization

•PCC coatings were verified to reduce inflammatory reaction and promote osteogenesis.•Sr-Zn-P B has an optimal topography and element composition for osteogenesis.•Cytokine-cytokine receptor interaction pathway may be the possible mechanism. The immune response of peri-titanium (Ti) implants, which is mainly determined by the surface properties of the Ti implant, may lead to a prolonged healing period and even implantation failure. The phosphate chemical conversion (PCC) technique is an effective method for simultaneously regulating the crystallographic morphological and elemental compositions of Ti implant surfaces. However, whether the PCC coating induces an immune response or further affects osteogenesis is unclear. In this study, we prepared three kinds of PCC-coated Ti implants, i.e., Sr-Zn-P A (strontium zinc phosphate with rectangular blocky crystals), Sr-Zn-P B (strontium zinc phosphate with lamellar crystals) and Sr-Ca-P (calcium strontium phosphate), which were composed of different phosphate crystals or had different morphologies. Although all PCC-coated Ti implants showed good biocompatibility with both rat bone marrow mesenchymal stem cells (rBMMSCs) and rat macrophages, different effects on rBMMSC osteogenesis and macrophage polarization were found in this study: 1) Sr-Zn-P B preferentially induced rBMMSC osteogenesis and M2 polarization to a greater extent than the other implants because of its surface morphology and ion release; 2) under three culture conditions (coculture, transwell and conditioned medium), Sr-Zn-P B was found to enhance the production of anti-inflammatory and pro-osteogenic factors via M2 polarization; 3) characterization of the osteogenesis and immune response in rat subcutaneous models and rat femoral defect models revealed that Sr-Zn-P B could perform well in osteoimmunomodulation in vivo; and 4) through RNA sequencing analysis, the up-/downregulation of several signaling pathways was identified as a potential reason for M2 polarization on Sr-Zn-P B. In conclusion, this study demonstrates that Sr-Zn-P B is a promising scaffold for osteoimmunomodulation and provides new insight into bone defect repair.