Mimicking Amelogenesis To Remineralize Enamel Through Cmc/Acp@Ptl Fibrils

Dental caries remains a global health challenge, affecting 60–90% of children and most adults. Existing biomimetic remineralization strategies fail to fully mimic the three "key events" of enamel formation, particularly neglecting the β-sheet structure and template function of amelogenin. This study aims to develop a novel strategy that mimics these key processes to achieve in-situ enamel remineralization with structural and mechanical properties comparable to natural enamel. Amyloid protein phase transited lysozyme fibrils were designed to mimic the role of amelogenin template, while acid carboxymethyl chitosan and sodium hypochlorite were utilized to simulate the role of non-amelogenin and proteolytic enzyme, respectively. A synchronous self-assembly and mineralization approach was employed to reconstruct the three "key events" of amelogenesis in vitro. In vivo experiments assessed biocompatibility and validity. The strategy successfully replicated the full process of the three "key events" of amelogenesis, achieving oriented enamel-like structures with mechanical properties close to natural enamel. In vitro remineralization occurred without external mineral ion supplementation. In vivo experiments confirmed the non-toxicity and biocompatibility of the material. Notably, amyloid conformation transition of amelogenin was identified critical for remineralization. This study presents a a promising and economical strategy for enamel regeneration that restores structural hierarchy and biomechanics, addressing limitations of current methods. By emphasizing amyloid-like templating and enzymatic regulation, it offers a non-invasive solution suitable for public health emergencies and special populations. The findings advance the understanding of mimicking amelogenesis and provide a clinically viable approach to combat dental caries.