Unravelling Doped Biphasic Calcium Phosphate: Synthesis to Application

Among synthetic biomaterials, calcium phosphate (CaP)-based bioceramics, specifically hydroxyapatite (HA) and tricalcium phosphate (TCP) as well as biphasic calcium phosphate (BCP), are widely investigated in the biomedical community. The arrangement of different ions in the CaP crystal structure allows one to dope with metal ions, while tailoring the properties. The present article reviews some of the multifaceted research in the field of (multi)-ion-doped BCP, particularly on the aspects of biomedical applications. After summarizing different synthesis methods, a brief overview of experimental techniques and results to probe the dopant site and local structure surrounding the dopants has been provided, with an emphasis on the XRD-based Rietveld refinement and EXAFS (extended X-ray absorption fine structure) method. The effect of ion substitution on the functional properties, such as dielectric and magnetic behavior, of BCP has also been discussed. Importantly, in vitro and in vivo biocompatibility of doped BCP has been elucidated along with in silico studies on the biomaterial-biomolecule interaction. Toward the end, the results of the published clinical trial study and limited commercialization efforts will be illustrated.