Self-Assembled Gel-like Aggregation States of Calcium Phosphate Nanoparticles

We proposed the fabrication of a gel composed primarily of calcium phosphate (CP) nanoparticles (NPs). Here, the additive of citric acid (Citr), which is an organic molecule present in bone tissues that chelates with calcium ions, was investigated during the synthesis of the CP NPs, with a focus on a gel-like aggregation state. As a result, the Citr-coordinated CP NP (Citr/CP NP) sols exhibiting different thermal responses ((1) maintenance of a sol state, (2) formation of a stable gel-like aggregation state, and (3) formation of a thixotropic gel-like aggregation state) were successfully prepared by controlling the nucleation and nanoparticle growth temperatures during the synthesis. Specifically, the sol of the highly anisotropic Citr/CP NP nucleated at 40 °C maintained its sol state after heat at 37.5 °C, whereas the isotropic Citr/CP NP at 4 °C formed the gel-like aggregation state upon the heat. The sol grown at 4 °C formed a stable gel-like aggregation state that was resistant to external force, whereas that at 40 °C exhibited thixotropy, which is a property commonly observed in synovial fluid. The gelation would be attributed to the precipitation of calcium citrate tetrahydrate, which exhibited retrograde solubility and promoted cross-linking among the CP NPs.