The Interplay between Diffusion Barrier and Nucleation Promotion during Noncarbonated and Carbonated Calcium Phosphate Mineralization in Polyacrylamide Hydrogels

Hydrogels serve as biomimetic platforms for studying calcium phosphate mineralization, a process that is essential to bone formation and biomaterial design. This study investigates how variations in the composition of polyacrylamide (pAAm) hydrogels (monomer and cross-linker concentration) influence the mineralization pathway, kinetics, and morphology of calcium phosphate under noncarbonated and carbonated conditions; the latter simulates the presence of carbonate during natural bone formation. Time-resolved scanning electron microscopy (SEM), X-ray diffraction (XRD), and Fourier transform infrared (FTIR) spectroscopy reveal that mineralization follows a consistent pathway across six hydrogel compositions. That is, amorphous calcium phosphate (ACP) initially forms and later transforms to hydroxyapatite (HAP). In carbonated systems, amorphous calcium carbonate (ACC) and sometimes transient vaterite act as precursors to ACP, delaying HAP crystallization due to the preceding ACC-to-ACP transformation and local pH effects. Regardless of the hydrogel composition, HAP exhibits two distinct morphologies: nanoplatelets adhering to the polymer and large hollow spherulites, suggesting two different pathways for the ACP-to-HAP transformation. Increasing the cross-linker concentration slows the onset of HAP crystallization by shifting the process from reaction- to diffusion-controlled. Diffusion-controlled mineralization leads to greater ACP retention, particularly at lower monomer concentrations (higher swelling ratios), while reaction-controlled mineralization accelerates HAP nucleation, increasing the HAP content with higher monomer concentrations. This results in opposite relationships between the mineral content and swelling ratio, offering a high degree of tunability. While the polymer network’s influence on HAP crystallization rate diminishes under carbonated conditions, the tunability still remains. These findings advance our understanding of biomineralization, with implications for diverse areas of inquiry, including pathological mineralization processes as well as biomaterial design for bone tissue engineering and therapeutic approaches to mitigate pathologies.