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

Enamel remineralization has important clinical value for the prevention and minimally invasive treat-ment of early enamel caries. Enamel matrix proteins (EMPs) are believed to play a key role in ameloge-nesis 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 hypochlo-rite (NaClO) mimicking non-amelogenin and proteolytic enzymes, respectively. Based on the syn-chronous 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 pro-posed the crucial role of the amyloid conformation transition of amelogenin and supported a promising biomimetic strategy for enamel repair.(c) 2023 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).