Surface Stability and Morphology of Calcium Phosphate Tuned by pH Values and Lactic Acid Additives: Theoretical and...

The ubiquitous mineralization of calcium phosphate (CaP) facilitates biological organisms to produce hierarchically structured minerals. The coordination number and strength of Ca²⁺ ions with phosphate species, oxygen-containing additives, and solvent molecules played a crucial role in tuning nucleation processes and the surface stability of CaP under the simulated body fluid (SBF) or aqueous solutions upon the addition of oligomeric lactic acid (LAC, n = 1, 8) and changing pH values. As revealed by ab initio molecular dynamics (AIMD), density functional theory (DFT), and molecular dynamics (MD) simulations as well as high-throughput experimentation (HTE), the binding of LAC molecules with Ca²⁺ ions and phosphate species could stabilize both the pre-nucleation clusters and brushite (DCPD, CaHPO₄·2H₂O) surface through intermolecular electrostatic and hydrogen bonding interactions. When the concentration of Ca²⁺ ions ([Ca²⁺]) is very low, the amount of the formed precipitation decreased with the addition of LAC based on UV-vis spectroscopic analysis due to the reduced chance for the LAC capped Ca²⁺ ions to coordinate with phosphates and the increased solubility in the acid solution. With the increasing [Ca²⁺] concentration, the kinetically stable DCPD precipitation was obtained with high Ca²⁺ coordination number and low surface energy. Morphologies of DCPD precipitation are in plate, needle, or rod, depending on the initial pH values that were tuned by adding NH₃·H₂O, HCl, or CH₃COOH. The prepared samples at pH ≈ 7.4 with different Ca/P ratios exhibited negative zeta potential values, which were correlated with the surface electrostatic potential distributions and potential biological applications.