Abstract
Surface nano-modification has emerged as an effective strategy to enhance osseointegration of titanium (Ti) implants. Despite its promise, rational optimization of surface nanomorphology for ameliorated osseointegration remains a significant challenge. Our research pioneering developed a one-step alkali etching technique to produce a gradient nanowire coating with continuously varied dimensions on Ti surfaces, which was subsequently served as a versatile platform for high-throughput screening of optimal dimensions to enhance osseointegration. The results showed that macrophages (MФs) that mainly governed the initial inflammatory reaction exhibited a polarization tendency towards pro-healing M2 phenotype with decreased nanowire dimension due to nanomorphology-mediated focal adhesion formation and activation of its downstream signaling pathways (typically PI3K-Akt). Simultaneously, small-sized nanowires with diameter of 5.63-14.25 nm and inter-spacing of 29.42-57.97 nm were conductive to angiogenesis of endothelial cells (ECs) and osteogenesis of bone marrow mesenchymal stem cells (BMSCs), which may share similar mechanisms of MФs. The in vivo results well corroborated these in vitro observations. The knowledge gained from the present work not only advance our understanding of the interaction between surface morphology and cells, but also potentially pave the way for efficient and cost-effective design of advanced biomaterial surfaces for better osseointegration.