Phase-Tunable Calcium Phosphate Biomaterials Synthesis and Application in Protein Delivery

Calcium phosphates (CaP) are important biomaterials used in tissue engineering and drug delivery, due to their biocompatibility, low toxicity, and osteoconductivity. However, controlling the phase of CaP, especially tricalcium phosphate (TCP), is very challenging under mild conditions, particularly when using one preparation protocol for all CaP phases. It is also crucial to produce these biomaterials economically and reproducibly. Herein, three of the most commonly employed CaP, including beta-tricalcium phosphate (β-TCP), dicalcium phosphate anhydrous (DCPA), and hydroxyapatite (HA) were, for the first time, successfully synthesized by altering the reaction solvent, using calcium acetate monohydrate as a precursor and a rapid microwave-assisted synthetic method. A variety of CaP particle morphologies were obtained, including elliptical and plate-shaped with different porosities. Compared with conventional heating, CaP biomaterials synthesized using microwave heating showed greater reproducibility, higher yields, and shorter reaction time. By varying the reaction solvents, morphologies and phases of CaP were controlled, leading to an enhanced protein bovine serum albumin (BSA) loading, with a higher BSA absorption observed according to the trend DCPA> β-TCP > HA. Furthermore, the phase, specific surface area, and pore size were shown to play decisive roles in protein desorption with a higher release amount observed according to the trend DCPA > β-TCP > HA. Finally, it is found that larger pores are also beneficial to BSA adsorption.