Bacterial S-layer protein inspired multifunctional peptide for dentin restoration via intrafibrillar mineralization facilitating.

Abstract

Intrafibrillar mineralization, essential for dentin restoration, necessitates precise coordination of microenvironmental factors. Current research on peptide-mediated collagen mineralization often lacks a comprehensive exploration of multifunctionality, focusing instead on isolated aspects such as self-assembly, nucleation ability, or collagen binding. Bacterial S-layer proteins, with their intrinsic self-assembly, collagen-binding features, and ion-capturing functions, offer a blueprint for integrating multifunctionality. Building on these features, we engineer a multifunctional self-assembly peptide (SlpB-21) that integrates essential capabilities to promote collagen mineralization. This innovative peptide synergistically enhances interactions with Ca²⁺ and type I collagen, driving the biomimetic process of intrafibrillar mineralization, which is critical for dentin restoration. Functioning as an "intermediate gripper", SlpB-21 efficiently assembles onto demineralized dentin collagen fibrils and directs ordered mineral deposition. Utilizing molecular dynamics simulations and stochastic optical reconstruction microscopy, the research systematically investigates the peptide's self-assembly, its mechanisms of interaction with collagen fibrils and Ca²⁺, and its role in mediating intrafibrillar mineralization. In vitro and in vivo experiments demonstrate the potential of SlpB-21 for biomimetic dentin repair. This study highlights SlpB-21 as a pioneering material for dentin restoration, introducing a novel strategy for biomimetic repair and offering promising avenues for treating early dentin caries.