Brushite cements are recognized for excellent osteoconductivity and rapid resorption rate, with improved bone regeneration capacity compared to hydroxyapatite-forming cements. Doping of biologically relevant ions in brushite has been performed to increase the mechanical and biological performance of bone substitutes.¹ Particularly, lithium (Li⁺) is a promising trace element to encourage the migration and proliferation of adipose-derived stem cells (hASCs) and the osteogenic differentiation-related gene expression, important for the osteogenesis. This study aims to investigate the osteogenic performance of new brushite cements obtained from Li⁺-doped β-tricalcium phosphate as a promising strategy for bone regeneration. The cements containing 5 mol.% Li⁺ were prepared with 3 wt.% phytic acid as setting retarder using liquid-to-powder ratio of 0.3 mL/g.² In-situ X-ray diffraction and in-situ 1H-nuclear magnetic resonance measurements proved the precipitation of brushite and monetite, indicating that Li⁺ favoured the formation of monetite under certain conditions. Li⁺ was detected in the remaining pore solution in significant amounts after completion of hydration. Isothermal calorimetry results showed an accelerating effect of Li⁺ with increasing setting retarder concentration. A decrease of initial and final setting times with increasing amount of Li⁺ and setting times could be well adjusted by means of varying the setting retarder concentration. In vitro assays using hASCs cultured on the powdered cements showed normal metabolic and proliferative levels. The immunodetection and gene expression profile of osteogenic-related markers highlights the incorporation of Li⁺ for increasing the in vivo bone density. Overall, the tunable properties of the developed Li⁺-doped brushite cements and its osteogenic potential evidenced by the significant up-regulation of Col I⍺ gene expression and ALP, show the promising benefits of these materials for bone regeneration, namely for filling bone defects.

References

1. K. Hurle, et al. Acta Biomaterialia, 123: 51-71, 2021. 

2. K Hurle, et al. Acta Biomaterialia, 80: 378, 2018.

Acknowledgments: Thanks to the Portuguese Foundation for Science and Technology and the German Academic Exchange Service for the transnational cooperation FCT/DAAD 2018-2019. Thanks to the Transitional Rule DL 57/2016 (CTTI-57/18-I3BS(5)), Junior Researcher contracts (POCI-01-0145-FEDER-031367; POCI-01-0145-FEDER-029139) under the projects Fun4TE project (PTDC/EMD-EMD/31367/2017) and B-Liver (PTDC/EMD-EMD/29139/2017), and for the distinctions IF/01285/2015 and CEECIND/03673/2017, attributed by FCT.