Lithium-doped brushite bone cements with improved biological performance

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 into brushite has been performed to increase the mechanical and biological performance of bone substitutes.¹ Particularly, lithium (Li⁺) is used to activate Wnt/β‐catenin and to inhibit glycogen synthase kinase-3β signaling pathways, leading to cell proliferation and bone formation. This study aims to develop novel Li⁺-doped brushite cements with enhanced mechanical and osteogenic properties 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 The results showed that the presence of Li⁺ led to a significant improvement of cements physicochemical properties and slightly lower setting time compared to pure cements. Only a minor influence on the cement setting reaction was observed, showing that the hydration reaction of the Li⁺ doped cement is slightly faster at 23ºC than at 37ºC. Still, Li⁺ doping did not affect the resulting phase composition at 37 °C. In vitro assays using human adipose-derived stem cells (hASCs) cultured on the powdered cements showed cell proliferation and osteogenic differentiation. High calcium deposition and alkaline phosphatase staining was evident for cells grown in the cements, cultured under osteogenic differentiation medium. These characteristics make the proposed brushite cements promising for use in orthopedics, namely for filling bone defects.

Acknowledgments: Thanks to the Portuguese Foundation for Science and Technology for FCT/DAAD 2018-2019 project and for the distinctions IF/01285/2015 and CEECIND/03673/2017.