Osteogenic lithium-doped brushite cements for bone regeneration

K. Hurle*, F. R. Maia, V. P. Ribeiro, S. Pina, J. M. Oliveira, F. Goetz-Neunhoeffer, R. L. Reis

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)


This study investigated the osteogenic performance of new brushite cements obtained from Li+-doped β-tricalcium phosphate as a promising strategy for bone regeneration. 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, essential for osteogenesis. In-situ X-ray diffraction (XRD) and in-situ 1H nuclear magnetic resonance (1H NMR) measurements proved the precipitation of brushite, as main phase, and monetite, indicating that Li+ favored the formation of monetite under certain conditions. Li+ was detected in the remaining pore solution in significant amounts after the completion of hydration. Isothermal calorimetry results showed an accelerating effect of Li+, especially for low concentration of the setting retarder (phytic acid). A decrease of initial and final setting times with increasing amount of Li+ was detected and setting times could be well adjusted by varying the setting retarder concentration. The cements presented compressive mechanical strength within the ranges reported for cancellous bone. In vitro assays using hASCs showed normal metabolic and proliferative levels. The immunodetection and gene expression profile of osteogenic-related markers highlight the incorporation of Li+ for increasing the in vivo bone density. The osteogenic potential of Li-doped brushite cements may be recommended for further research on bone defect repair strategies.

Original languageEnglish
Pages (from-to)403-417
Number of pages15
JournalBioactive Materials
Publication statusPublished - Oct 2022
Externally publishedYes


  • Alkaline phosphatase activity
  • Bone regeneration
  • Brushite cements
  • Collagen expression
  • Lithium doping
  • Osteogenic expression
  • β-tricalcium phosphate


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