Tricalcium phosphate doped with Mg2+ and combinations of Mn2+, Zn2+ and Fe3+: A DoE study on sintering, mechanical, microstructural and biological properties

Bioactive ceramics such as tricalcium phosphate (TCP) doped with metal ions are often used to replace natural bone in orthopedic and dental function, both in structural and coating applications. Although the addition of different ions to TCP has been correlated with improved mechanical performance, as well as pro-osteogenic and osteointegrative biological activities, the effect of combining different ions in single biomaterial formulations is poorly described. Here, design of experiments (DoE) was used to assess the effect of the addition of three metallic ions - Mn2+, Zn2+ and Fe3+ - to TCP doped with 10 mol% Mg2+, in combinations comprising one, two and three ions with varying ratios. Our results showed that the TCP could be doped by combinations of metallic ions and β-TCP and hydroxyapatite constitute the main crystalline phases. Additionally, the simultaneous effect of metal ions influenced the structural and physical properties of the TCP composite. Overall, for up 1 mol% of Mn2+, up to 3.75 mol% of Zn2+ and more than 2 mol% of Fe3+, compositions 2 and 6, a dense microstructure and good defined grain boundaries improve the mechanical properties. Furthermore, the ion-doped TCP composites, namely the one prepared from equal amounts of substituting ions besides Mg2+, did not elicit a cytotoxic effect indicating that these materials could be of interest for tissue engineering applications published