Ag-containing high-entropy nitride coatings promote bone regeneration by mediating the MAPK/ERK signaling pathway

Bone defect repair presents a significant clinical challenge in oral and maxillofacial surgery and orthopedics. Implant-associated infection and insufficient osseointegration often compromise clinical outcomes, while traditional repair materials still struggle to simultaneously provide mechanical support, antibacterial activity, and osteogenic efficacy. This study employed magnetron sputtering to fabricate high-entropy nitride (HEN) coatings with varying silver (Ag) contents. Among these, the stable single-phase solid solution (TiZrNbHfTaAg)N coating with 5.7 at. percentage (at%) Ag exhibited outstanding comprehensive properties. This coating combines favorable biocompatibility with potent antibacterial activity, exhibiting antibacterial rates of 90.6% and 97.1% against common oral pathogens F. nucleatum and P. gingivalis, respectively. It also promotes osteoblast differentiation and mineralization by activating the MAPK/ERK signaling pathway, thereby upregulating the expression of genes and proteins associated with osteogenesis. In vivo validation using a rabbit tibia defect model showed that implantation of the (TiZrNbHfTaAg)N coating significantly improved indicators of bone regeneration and osseointegration strength. This coating offers a novel surface modification approach to address bone defect repair challenges through its "antibacterial-osteogenic" synergistic effect and bone regeneration mechanism mediated by the MAPK/ERK pathway, demonstrating considerable potential for clinical translation.