Abstract

Nanomesh topology-mediated physical interlock on Ti implants can simultaneously enhance soft tissue seal and osseointegration • Physical interlocking can activate YAP/TAZ mechanotransduction cascade, further enhancing cell osteogenic differentiation • Surface modification achieves synergistic optimization with enhanced soft tissue seal, osseointegration and low inflammation Peri-implant inflammation caused by poor soft tissue sealing remains the major cause of titanium (Ti) implant failure. Inspired by Sharpey's fibers in natural periodontal tissues, developing new strategies that could mimic such anchorage structures merely through physical surface topography remains a key challenge. Herein, we fabricated the nanosheet, nanowire, and nanomesh structures on Ti surfaces by alkali etching under different reaction times. Unlike conventional biochemical modifications, we functionalized the Ti substrates simply through microstructural modification. The results displayed that the nanomesh structure exhibited the highest macroscopic roughness, which is beneficial for forming stable gingival fibroblast adhesion via macrostructure-mediated physical interlocking, as evidenced by the upregulated expression of integrin β4/α6, along with evaluated levels of plectin and laminin α3, confirming coordinated assembly of hemidesmosomal adhesion complexes. Further analysis revealed that such interlocked cellular adhesion could activate the YAP/TAZ mechanotransduction signaling pathway and enhance the nuclear accumulation of YAP protein, thus providing important molecular basis for initiating downstream cellular processes such as proliferation and differentiation. Simultaneously, this mechanotransduction cascade could also enhance the osteogenic differentiation of MC3T3-E1 cells. Compared with other surface structure, the in vivo experimental results further demonstrated that the nanomesh structured Ti implants exhibited the tightest soft tissue integration with the peri-implant at th