Mimicking amelogenesis to remineralize enamel through co-assembly of PTL fibrils and CMC/ACP

Abstract

Enamel remineralization has important clinical value for the prevention and minimally invasive treatment of early enamel caries. Enamel matrix proteins (EMPs) are believed to play a key role in amelogenesis to regulate the growth and organization of enamel. Three “key events” of amelogenesis indicated the co-assembly of EMPs composed of amyloid amelogenin (templating protein) and non-amelogenin (non-templating protein) with amorphous calcium phosphate (ACP), followed by the transformation into the crystalline phase with the help of proteolytic enzymes. Herein, a biomimetic microenvironment is constructed, adhesive phase-transited lysozyme fibrils (PTL fibrils) mimicking amelogenin template through amyloid-like lysozyme aggregation, acid carboxymethyl chitosan (CMC) and sodium hypochlorite (NaClO) mimicking non-amelogenin and proteolytic enzymes, respectively. Based on the synchronous self-assembly and mineralization, the full process of the three “key events” of biomineralization were reverted in vitro by slowly raising the pH of the system through dialysis, in-situ regenerating enamel-like crystals with properly oriented structure and mechanical properties that are close to natural enamel independent of additional mineral ions. Especially, the present study proposed the crucial role of the amyloid conformation transition of amelogenin and supported a promising biomimetic strategy for enamel repair.