Abstract: Three-dimensional (3D) printing is serving as the most promising approach to fabricate personalized titanium (Ti) implants for the precise treatment of complex bone defects. However, the bio-inert nature of Ti material limits its capability for rapid osseointegration and thus influences the implant lifetime in vivo. Despite the macroscale porosity for promoting osseointegration, 3D-printed Ti implant surface morphologies at the nanoscale have gained considerable attention for their potential to improve specific outcomes. To evaluate the influence of nanoscale surface morphologies on osseointegration outcomes of 3D-printed Ti implants and discuss the available strategies, we systematically searched evidence according to the PRISMA on PubMed, Embase, Web of Science, and Cochrane (until June 2022). The inclusion criteria were in vivo (animal) studies reporting the osseointegration outcomes of nanoscale morphologies on the surface of 3D-printed Ti implants. The risk of bias (RoB) was assessed using the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE’s) tool. The quality of the studies was evaluated using the Animal Research: Reporting of In Vivo Experiments (ARRIVE) guidelines. (PROSPERO: CRD42022334222). Out of 119 retrieved articles, 9 studies met the inclusion criteria. The evidence suggests that irregular nano-texture, nanodots and nanotubes with a diameter of 40– 105nm on the surface of porous/solid 3D-printed Ti implants result in better osseointegration and vertical bone ingrowth compared to the untreated/polished ones by significantly promoting cell adhesion, matrix mineralization, and osteogenic differentiation through increasing integrin expression. The RoB was low in 41.1% of items, unclear in 53.3%, and high in 5.6%. The quality of the studies achieved a mean score of 17.67. Our study demonstrates that nanostructures with specific controlled properties on the surface of 3D-printed Ti implants improve their osseointegration. However, given the small number of studies, the variability in experimental designs, and lack of reporting across studies, the results should be interpreted with caution.
Keywords: nano-pattern, 3D-printed, titanium implant, surface modification, osseointegration