Spatially Controlled Supersaturation of Calcium Phosphate for Controlled Crystal Nucleation and Self-Healing Precipitates

Crystal nucleation and growth are widely studied phenomena due to their relevance to a range of disciplines including material science, process engineering, and biology. In order to obtain desirable crystal forms or crystallization dynamics, it is essential to tune parameters like nucleation time, nucleation rate, and growth rate. Supersaturation of material in the crystallizing solution is the first step in the crystallization process, and impacts all these parameters, hence controlling supersaturation is crucial to controlling the overall process of crystallization (1). Some common methods to achieve supersaturation include subjecting a solution to: evaporation, cooling (for materials with temperature-dependent solubility), the addition of antisolvents, and pH change (for materials with pH-dependent solubility). These methods typically result in supersaturation within the primary solution. However, in some systems such as biomineralization or studies probing nucleation dynamics, nucleation is required at specific locations, often outside the region where the primary solution composition can be easily actively controlled. This motivates the development of strategies to create localized supersaturated conditions.<br/>In this study, we present a straightforward approach that enables spatially controlled deposition of precipitated material between two primary solutions (2). Our experimental setup focuses on calcium phosphate (CAP) as a prototypical system, taking advantage of its pH-dependent solubility. By connecting two saturated solutions at different pHs using a gel that allows ion diffusion, we establish a concentration gradient along the gel. The diffusion and reaction of H⁺ and OH^- create a characteristic pH profile along the length of the gel, causing the diffusing calcium and phosphate to become supersaturated and precipitate. Over time, the precipitated band grows denser and forms a barrier that restricts further transport through the gel. We show how this band spontaneously recovers from perturbation, automatically resealing any damage. In addition to experiments, we perform quantitative analysis taking into consideration the diffusion dynamics of all the relevant ions, chemical equilibria, and reaction parameters, to predict the location of the precipitated bands. This work provides a simple physical strategy for creating self-healing precipitates that may be useful in civil engineering, restorative dentistry, and enhancing our understanding of mineral deposit formation in the abiotic and living world.<br/><br/><b>References:</b><br/>(1) Mullin, J.W. Crystallization, Fourth Edition, p. 315, 2001.<br/>(2) Wagner M.; Hess, T.; Zakowiecki, D.; Studies on the pH-Dependent Solubility of Various Grades of Calcium Phosphate-based Pharmaceutical Excipients, J. Pharm. Sci, 2022.