Dentin hypersensitivity (DH) originates from collagen exposure and dentinal tubules (DTs) patency caused by mechanical abrasion or demineralization. For an effective long-term therapeutic desensitizing agent, the ability to achieve deep tubular occlusion, stable remineralization, and satisfactory biocompatibility simultaneously is essential. In this study, we designed a novel α-hairpin peptide, TKH, engineered by incorporating a flexible GKG linker into an α-helical template, and provide an analysis of its liquid-liquid phase separation (LLPS) and self-assembly properties. TKH effectively stabilized amorphous calcium phosphate and facilitated intrafibrillar mineralization within collagen fibrils. In vitro and in vivo remineralization studies combined with molecular dynamics (MD) simulations demonstrated that TKH promoted the peptide self-assembly through LLPS, hydroxyapatite (HA) adsorption, and amorphous calcium phosphate (ACP) stabilization, ultimately achieving intrafibrillar and extrafibrillar mineralization to seal DTs, alongside excellent biosafety. These findings highlight the potential of TKH as a promising peptide-based biomaterial for dentin remineralization and the treatment of dentin hypersensitivity.
Ou et al. (Thu,) studied this question.