How to build a bone? - Hydroxyapatite or Posner’s clusters as bone minerals

For decades, hydroxyapatite has been considered the main mineral phase of mammalian tooth enamel and bone that crystallizes from a precursor phase, amorphous calcium phosphate. Amorphous calcium phosphate, in turn, is proposed to be made from small clusters of ions known as Posner’s clusters, with a size of 0.95 ​nm and chemical formula of Ca9(PO4)6. In isolation, Posner’s clusters are extremely unstable and spontaneously aggregate and nucleate to the thermodynamically stable phase of hydroxyapatite within a few seconds. In this critical review, we will discuss the progress made in identifying the role of Posner’s clusters in the bone mineralization process, visualization of the clusters and associated challenges, and potential pathways to utilize them in bone tissue engineering strategies. We hypothesize, based on collective data in the literature and our recent experimental data, that Posner’s cluster agglomerates and amorphous calcium phosphate particles are in fact the main mineral component of bone, and hydroxyapatite crystals are, in part, artefacts of sample processing.