Silicon Nitride Nanofilm Functionalized Titanium Mesh for Boosting Osseointegration by Macrophage-Related Immunomodulation

Abstract Titanium mesh-supported guided bone regeneration (TM-GBR) has emerged as a clinically effective strategy for alveolar bone augmentation in complex defects, primarily through its ability to preserve osteogenic space and correct bone volume deficiencies. However, due to the inherent biological inertness of titanium mesh (TM), insufficient osteoinductive at the interface of TM remains a pressing issue to be addressed in alveolar bone reconstruction. Herein, silicon nitride nanofilms with low (SiN55), medium (SiN65), and high (SiN75) nitrogen contents were fabricated on TM substrates via reactive magnetron sputtering, exhibiting favorable hydrophilicity, superior corrosion resistance, and antibacterial activity. Moreover, the SiN65 nanofilms significantly promoted the macrophage polarization from the pro-inflammatory M1 phenotype to the pro-regenerative M2 phenotype and enhanced osteogenic differentiation through immune regulation of macrophages in co-culture assays. Mechanistically, RNA-eq analysis revealed that the SiN65 nanofilms modulated macrophage differentially expressed genes and reprogrammed the protein−protein interaction network, accompanied by downregulation of TNF, JAK-STAT, and Toll-like receptor signaling pathways. Additionally, the SiN65 nanofilms promoted bone regeneration in rat calvarial defect models. This study presents the SiN65 nanofilms as a rationally engineered coating integrating immunomodulatory and osteogenic functions, effectively mitigating peri-implant fibrosis and providing a promising strategy to improve the long-term outcomes of TM-GBR.