The current study compares biocompatibility, cell growth and morphology, pore diameter distribution, and interconnectivity of a novel titanium dioxide (TiO₂) bone graft substitute granules with three different commercially available bone graft granules Natix^®, Straumann^® BoneCeramic, and Bio-Oss^®. Human primary mesenchymal stem cells were cultured on the bone graft substitutes and cell viability and proliferation were evaluated after 1 and 3 days. The microstructural properties of the bone graft substitutes were evaluated by scanning electron microscopy, micro-computed tomography analysis, and mechanical testing. The cell viability and proliferation, porosity, interconnectivity, open pore size, and surface area-to-volume ratio of TiO₂ granules were significantly higher than commercial bone granules (Bio-Oss^® and Straumann ^® BoneCeramic).