β-tricalcium phosphate for bone substitution: Synthesis and properties

β-tricalcium phosphate (β-TCP) is one the most used and potent synthetic bone graft substitute. It is not only osteoconductive, but also osteoinductive. These properties, combined with its cell-mediated resorption, allow full bone defects regeneration. Its clinical outcome is sometimes considered to be "unpredictable", possibly due to a poor understanding of β-TCP physico-chemical properties: β-TCP crystallographic structure is not fully uncovered; recent results suggest that sintered β-TCP is coated with a Ca-rich alkaline phase; β-TCP apatite-forming ability and osteoinductivity may be enhanced by a hydrothermal treatment; β-TCP grain size and porosity are strongly modified by the presence of minute amounts of β-calcium pyrophosphate or hydroxyapatite impurities. The aim of the present article is to provide a critical, but still rather comprehensive review of the current state of knowledge on β-TCP, with a strong focus on its synthesis and physico-chemical properties, and their link to the in vivo response. STATEMENT OF SIGNIFICANCE: The present review documents the richness, breadth, and interest of the research devoted to β-tricalcium phosphate (β-TCP). β-TCP is synthetic, osteoconductive, osteoinductive, and its resorption is cell-mediated, thus making it one of the most potent bone graft substitutes. This comprehensive review reveals that there are a number of aspects, such as surface chemistry, crystallography, or stoichiometry deviations, that are still poorly understood. As such, β-TCP is still an exciting scientific playground despite a 50 year long history and > 200 yearly publications.