Citrate Improves Biomimetic Mineralization Induced by Polyelectrolyte–Cation Complexes Using PAsp‐Ca&Mg Complexes

Magnesium ions are highly enriched in early stage of biological mineralization of hard tissues. Paradoxically, hydroxyapatite (HAp) crystallization is inhibited significantly by high concentration of magnesium ions. The mechanism to regulate magnesium‐doped biomimetic mineralization of collagen fibrils has never been fully elucidated. Herein, it is revealed that citrate can bioinspire the magnesium‐stabilized mineral precursors to generate magnesium‐doped biomimetic mineralization as follows: Citrate can enhance the electronegativity of collagen fibrils by its absorption to fibrils via hydrogen bonds. Afterward, electronegative collagen fibrils can attract highly concentrated electropositive polyaspartic acid‐Ca&Mg (PAsp‐Ca&Mg) complexes followed by phosphate solution via strong electrostatic attraction. Meanwhile, citrate adsorbed in/on fibrils can eliminate mineralization inhibitory effects of magnesium ions by breaking hydration layer surrounding magnesium ions and thus reduce dehydration energy barrier for rapid fulfillment of biomimetic mineralization. The remineralized demineralized dentin with magnesium‐doped HAp possesses antibacterial ability, and the mineralization mediums possess excellent biocompatibility via cytotoxicity and oral mucosa irritation tests. This strategy shall shed light on cationic ions‐doped biomimetic mineralization with antibacterial ability via modifying collagen fibrils and eliminating mineralization inhibitory effects of some cationic ions, as well as can excite attention to the neglected multiple regulations of small biomolecules, such as citrate, during biomineralization process. Citrates absorption endow collagen fibrils with more negative charges. Electrostatic attraction provides a driving force for positively charged PAsp‐Ca&Mg complexes to infiltrate into collagen. Moreover, citrates break the hydration layer of magnesium ions that can reduce the nucleation barrier and thus promote crystallization of Mg‐doped biomimetic dentin mineralization.