Tuning the Intrafibrillar Collagen Mineralization Rate and Mechanical Properties Through Polyelectrolyte‐Controlled Formation and Crystallization of Amorphous Precursor

Abstract Non‐collagenous proteins (NCPs) play a crucial role in directing intrafibrillar collagen mineralization during hard tissue formation, however, their functions and control mechanisms remain elusive and controversial. Here, employing poly(allylamine hydrochloride) (PAH) as the NCPs analog, the potential correlation between the precursor crystallization process and the intrafibrillar collagen mineralization process controlled by NCPs/NCPs analogs, as well as its effects on kinetics and mechanical properties are systematically investigated. Results demonstrate that liquid–liquid phase separation of PAH and phosphate ions promotes the formation of amorphous calcium phosphate (ACP) liquid precursor and controls their composition, size, and physicochemical properties. These amorphous precursor are not stable at low PAH concentrations and quickly transform into small‐sized hydroxyapatite, while high concentrations prolong phase transition and induce the formation of large aggregated crystals. Interestingly, PAH can infiltrate into collagen fibrils along with ACP, thus oppositely regulating collagen fibrils mineralization rate and mechanical characteristics, where low amounts of PAH mediate rapid intrafibrillar mineralization with qualified hardness and modulus, while high amounts of PAH mediate slow intrafibrillar mineralization with improved mechanical properties. This work provides a dynamic perspective for understanding NCPs‐regulated hard tissue formation and opens new horizons for optimizing biomimetic mineralization materials fabrication and biomimetic repair.