Stabilization of Calcium Oxalate Precursors during the Pre- and Post-Nucleation Stages with Poly(acrylic acid)

Abstract

In this work, calcium oxalate (CaOx) precursors were stabilized by poly(acrylic acid) (PAA) as an additive under in vitro crystallization assays involving the formation of pre-nucleation clusters of CaOx via a non-classical crystallization (NCC) pathway. The in vitro crystallization of CaOx was carried out in the presence of 10, 50 and 100 mg/L PAA by using automatic calcium potentiometric titration experiments at a constant pH of 6.7 at 20 °C. The results confirmed the successful stabilization of amorphous calcium oxalate II and III (ACOII and ACO III) nanoparticles formed after PNC in the presence of PAA and suggest the participation and stabilization of polymer-induced liquid-precursor (PILP) in the presence of PAA. We demonstrated that PAA stabilizes CaOx precursors with size in the range of 20–400 nm. PAA additive plays a key role in the in vitro crystallization of CaOx stabilizing multi-ion complexes in the pre-nucleation stage, thereby delaying the nucleation of ACO nanoparticles. Indeed, PAA additive favors the formation of more hydrated and soluble phase of ACO nanoparticles that are bound by electrostatic interactions to carboxylic acid groups of PAA during the post-nucleation stage. These findings may help to a better understanding of the pathological mineralization resulting in urolithiasis in mammals.

Insight on the Role of Poly(acrylic acid) for Directing Calcium Phosphate Mineralization of Synthetic Polymer Bone Scaffolds

“…Since calcium ions that are sequestered by PAA are not detected by the probe, the ion-complexing behavior of the PAA could be measured. As seen in Figure a, the measured free Ca 2+ concentration decreases as the solution concentration of PAA increases, which is consistent with studies of Ca 2+ titration into a PAA-containing solution . Three PAA molecular weights were used for this study (1.8, 100, and ∼250 kDa, abbreviated as PAA 1.8 , PAA 100 , and PAA 250 ).…”

“…As seen in Figure 5a, the measured free Ca 2+ concentration decreases as the solution concentration of PAA increases, which is consistent with studies of Ca 2+ titration into a PAA-containing solution. 46 Three PAA molecular weights were used for this study (1.8, 100, and ∼250 kDa, abbreviated as PAA 1.8 , PAA 100 , and PAA 250 ). For PAA 100 and PAA 250 , more than 50% of available calcium is sequestered when the PAA concentration is 1000 μg/mL.…”

Liquid-Liquid Phase Separation in Nucleation Process of Biomineralization

“…A number of patients suffered from pathological biomineralization such as kidney stones and gallstones, and few useful prevention methods could be applied. Díaz-Soler et al (2021) found that calcium oxalate precursors, which are the main component of kidney stones, could be stabilized by polyacrylic acid (PAA) by forming an LLPS-dependent PILP process. They found that PAA could stabilize the multi-ion complexes, and so that delaying the nucleation process.…”

Elucidating the role of hyaluronic acid in the structure and morphology of calcium oxalate crystals

“…The COD form is often present in the urine of healthy subjects while COM calculi are more prevalent in the urine of recurrent stone formers compared with urine from healthy subjects [14,15]. Thus, recent reports focused on how natural and synthetic additives, for example, amino acids [16][17][18][19], polymers [20,21], lipids [22], proteins [23,24], peptides [25,26], metal ions [27][28][29], and carboxylic acids [30,31], affect the formation of the different forms of CaOx and how they can be leveraged to prevent or treat kidney stones. Various additives show specific binding with different surfaces of the CaOx crystals and can inhibit their growth via various mechanisms [32].…”