Effects of the Dental Implant Surface Topography and Macrophage Polarisation on Osteogenesis and Angiogenesis

INTRODUCTION AND AIMS: We aimed to investigate the effects of micro-nano surface of titanium (Ti) implant on macrophage polarisation, osteogenesis and angiogenesis in the peri-implant microenvironment, and to explore the underlying mechanism. METHODS: Ti disks with a micro-nano hybrid topography were characterised using scanning electron microscopy (SEM). Cell viability of macrophages was detected by CCK-8 assay. Macrophage polarisation was assessed on these surfaces via quantitative reverse transcription PCR (RT-qPCR) and immunofluorescence. The osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) and angiogenic capacity of human umbilical vein endothelial cells (HUVECs) were evaluated using conditioned medium from macrophages cultured on the Ti disks. Finally, the osteoimmunomodulatory effects of the micro-nano Ti implants were validated in a rat alveolar bone defect model, with bone formation and inflammatory response analysed by micro-CT and histology. RESULTS: Surface characterisation confirmed the successful fabrication of a hybrid micro-nano topography. This specific topography of the Ti disk promoted the M2 polarisation of macrophages, as evidenced by the upregulation of CD206/Arg1 and downregulation of iNOS/TNF-α/IL-6. Conditioned medium from these M2 macrophages enhanced the osteogenic differentiation of BMSCs and boosted the migration and tube formation of HUVECs. Consistently, in vivo implantation led to increased new bone formation and a reduced inflammatory response. Mechanistically, the micro-nano surface topography mediated macrophage polarisation via the YAP/Piezo1/AKT/ERK signalling axis. CONCLUSIONS: The micro-nano surface topography of Ti implants can promote M2 polarisation of macrophages and potentially promote osteogenic differentiation of BMSCs and angiogenesis of HUVECs, which may be related to the activation of YAP/Piezo1/AKT/ERK signalling axis. CLINICAL RELEVANCE: This study presents a promising strategy for improving osseointegration and angiogenesis in clinical dental implant applications. By promoting M2 polarisation of macrophages and reducing inflammation, micro,nano-surefced implants may minimise implant failure rate and enhance long-term functional outcomes, particularly for patients with bone deficiency.