Micro/nanometer-sized porous structure of zinc phosphate incorporated Ti(HPO4)2 hydrate bioceramic induces osteogenic gene expression and enhances osteoporotic bone regeneration

• Bio-actuated Ti(HPO 4 ) 2 /Zn 3 (PO 4 ) 2 (0.1).nH 2 O bioceramic was synthesized. • Bone-mimicking structure of phosphate-rich bioceramic improved bone cells proliferation. • Controlled released of Zn ++ stimulates cells for up-regulation of osteogenic genes expression. • Osteoinduction of the bioceramic increased bone mineralization and new bone formation. In this work, we describe the synthesis of an ideal bioceramic to which cells can easily respond that has geometry and composition that are similar to those of bone-like apatite. The successful preparation of bone-inspired titanium hydrate phosphate with an optimized weight percentage (∼1.1 wt.%) of zinc in (Ti(HPO 4 ) 2 /Zn 3 (PO4) 2 .nH 2 O) bioceramic could represent a potential regenerative framework for bone defect repair and bone void filler that would be useful for various clinical approaches. We have for the first time demonstrated the detailed physicochemical and biological characterizations of the bioceramic required to achieve a biocompatible and porous architecture that is similar to hydroxyapatite. In vitro studies have shown that the phosphate-rich titanium and zinc nanocomposite promote bone regeneration after stimulating MC3T3−E1 and hBM-MSCs cells activity. The metallic ions and phosphate had the effects of enhancing the cell viability and osteogenic differentiation of the cells, as confirmed by the expression of bone-related markers that included ALP, Col1a1, RUNX2, OPN/Spp1, and OCN through qRT-PCR, Western blotting, and immunocytochemistry. Moreover, the bioceramic has been shown to significantly improves new bone growth in critical size calvarial defect in rat model. The findings of the present work are the first that show the bone regeneration effect of bioceramic, which could be crucial for subsidies of Ca–P-based artificial bone implant materials. Our results provide insight into the Ti(HPO 4 ) 2 /Zn 3 (PO4) 2 (0.1).nH 2 O bioceramic in osteogenesis which can help to establish a therapeutic strategy in bone tissue regenerative medicine.