Exploring the Formation Kinetics of Octacalcium Phosphate from Alpha-Tricalcium Phosphate: Synthesis Scale-Up, Determination of Transient Phases, Their Morphology and Biocompatibility

Even with decades of research studies behind octacalcium phosphate (OCP), determination
of OCP phase formation has proved to be a cumbersome challenge. Even though obtaining a large
quantity of OCP is important for potential clinical uses, it still remains a hindrance to obtain high
yields of pure OCP. Taking that into consideration, the purpose of this study was to scale-up OCP
synthesis for the first time and to use a multi-technique approach to follow the phase transformation
pathway at multiple time points. In the present study, OCP has been synthesized from -tricalcium
phosphate (-TCP), and subsequently scaled-up tenfold and hundredfold (100 mg ! 10 g). The
hydrolysis mechanism has been followed and described by using XRD and FTIR spectroscopy, as
well as Raman and SEM. Gradual transformation into the OCP phase transpired through dicalcium
phosphate dihydrate (brushite, DCPD, up to ~36%) as an intermediary phase. Furthermore, the
obtained transitional phases and final OCP phases (across all scale-up levels) were tested with
human bone marrow-derived mesenchymal stem cells (hBMSCs), in order to see how different phase
mixtures affect the cell viability, and also to corroborate the safety of the scaled-up product. Twelve
out of seventeen specimens showed satisfactory percentages of cell viability and confirmed the
prospective use of scaled-up OCP in further in vitro studies. The present study, therefore, provides
the first scale-up process of OCP synthesis, an in depth understanding of the formation pathway, and
investigation of the parameters able to contribute in the OCP phase formation.