Calcium phosphate (CaP) minerals are primarily found in skeletons. In vivo, several compounds from this family have been identified: amorphous calcium phosphate, hydroxyapatite, octacalcium phosphate, to name a few. Ex vivo, many more crystal phases have been synthesized. This ability to obtain synthetic minerals that have a composition close to those found in human bones has led to many successful innovations in bone repair and regeneration. However, not only are the in vivo biomineralization paths still not completely understood, but also current bone repair strategies need to be improved in terms of healing time and bone-mimicking biological and mechanical responses. 

While studying the phase transformation of an amorphous intermediate of CaP, an international team led by Bing-Qiang Lu and Denis Gebauer from the Shanghai Institute of Ceramics, China, and from Leibniz University Hannover, Germany, discovered another metastable form of CaP. This new crystalline form of CaP, dicalcium phosphate monohydrate (DCPM, CaHPO₄, H₂O) transforms into hydroxyapatite—the stable CaP phase found in human bone—within only one hour after immersion in water. This is twice as fast as the dicalcium phosphate dihydrate (DCPD) phase usually used in bone cements today. Also, DCPM can be stabilized by organic molecules such as citrate salts, highly abundant in the human body. Finally, DCPM can adsorb a large quantity of small molecules. These particularities make DCPM interesting for encapsulation and release of drugs, for example to enhance bone healing and remineralization. The researchers reported their discovery in a recent issue of Nature Communications. 

The formation of DCPM was achieved using a mixture of ethanol and water that maintained a low level of hydration and inhibited the formation of DCPD. The crystal structure was revealed by continuously rotating the DCPM crystals and collecting a series of selected-area electron diffraction patterns in a transmission electron microscope (TEM). Tom Willhammar, co-first author of the article, explained that despite the metastability of DCPM,  “the humidity seems to be a crucial factor. In the TEM, we are operating under high vacuum conditions which might help keep DCPM stable.”  Figure (a) shows a TEM image of a DCPM crystal, and Figure b shows the reconstructed crystal structure. 

Although DCPM opens up new questions on biomineralization processes and potential strategies for bone tissue engineering, the next work of the research group is to explore the transformation behavior of DCPM in solution further, before turning to studying the potential roles of the new CaP in vivo. 

Sergio Bertazzo, a lecturer at University College London, UK, and specialist in the study of calcified tissues, who was not part of this study, says that hydroxyapatite, as obtained after conversion of DCPM, “is also the main component of pathological calcifications such as the ones present in cardiac diseases and cancers. In practically all calcific diseases, the formation and origins of the mineral component are unknown. The discovery of DCPM may contribute to a better understanding of the origins and mechanisms of formation of these minerals.” 

Read the article in Nature Communications.