Additively manufactured titanium scaffolds and osteointegration - meta-analyses and moderator-analyses of in vivo biomechanical testing

INTRODUCTION: Maximizing osteointegration potential of three-dimensionally-printed porous titanium (3DPPT) is an ongoing focus in biomaterial research. Many strategies are proposed and tested but there is no weighted comparison of results. METHODS: We systematically searched Pubmed and Embase to obtain two pools of 3DPPT studies that performed mechanical implant-removal testing in animal models and whose characteristics were sufficiently similar to compare the outcomes in meta-analyses (MAs). We expanded these MAs to multivariable meta-regressions (moderator analysis) to verify whether statistical models including reported scaffold features (e.g., “pore-size”, “porosity”, “type of unit cell”) or post-printing treatments (e.g., surface treatments, adding agents) could explain the observed differences in treatment effects (expressed as shear strength of bone-titanium interface). RESULTS: “Animal type” (species of animal in which the 3DPPT was implanted) and “type of post-treatment” (treatment performed after 3D printing) were moderators providing statistically significant models for differences in mechanical removal strength. An interaction model with covariables “pore-size” and “porosity” in a rabbit subgroup analysis (the most reported animal model) was also significant. Impact of other moderators (including “time” and “location of implant”) was not statistically significant. DISCUSSION/CONCLUSION: Our findings suggest a stronger effect from porosity in a rat than in a sheep model. Additionally, adding a calcium-containing layer does not improve removal strength but the other post-treatments do. Our results provide overview and new insights, but little narrowing of existing value ranges. Consequent reporting of 3DPPT characteristics, standardized comparison, and expression of porosity in terms of surface roughness could help tackle these existing dilemmas. GRAPHICAL ABSTRACT: [Image: see text]