Biomimetic control of hydroxyapatite crystallization by chondroitin sulfate for enamel remineralization

Chondroitin sulfate mediates the amorphous calcium phosphate ordered assembly. • Chondroitin sulfate directs the oriented crystallization of the hydroxyapatite. • Biomimetic restores the enamel hierarchical structure and mechanical properties. • Hydrogel mineralization system demonstrates significant efficacy for enamel repair. Objectives This study aims to develop a biomimetic mineralization strategy using chondroitin sulfate (CS) to reconstruct the intricate hierarchical structure of enamel and restore its mechanical properties. Methods Demineralized enamel was remineralized in a CS-containing artificial saliva (AS). The crystallization of hydroxyapatite (HAP) in AS was investigated using transmission electron microscopy (TEM) and atomic force microscopy (AFM)-infrared spectroscopy. Enamel repair efficacy was systematically evaluated via scanning electron microscopy (SEM) and AFM to characterize the microstructure and repair thickness, while nanoindentation was employed to quantify the mechanical properties. In addition, acid resistance was evaluated using a 50 mM HCl solution. Furthermore, an AS-hydrogel mineralization system was developed to evaluate its efficacy in restoring demineralized enamel under biologically relevant conditions. Results The results demonstrate that CS-modified ACP successfully assembles into chain-like precursors via anisotropic forces, which simultaneously regulate the oriented crystallization of HAP. This strategy resulted in a newly formed mineralized layer that effectively reconstructs the hierarchical architecture and recovers mechanical properties, including hardness, elastic modulus, and coefficient of friction, to near-native levels. In addition, the repaired enamel exhibits an acid resistance level comparable to that of native enamel. Significance This study establishes a new, mechanism-driven strategy for enamel remineralisation that is mediated by CS, and a corresponding hydrogel mineralization system, which can be translated into practice, offering a promising approach to future clinical enamel restoration. Download: Download high-res image (411KB) Download: Download full-size image