Hierarchical Mineralization Buffer Zone for Dentin Interface Reconstruction via Protein‐Guided Nonclassical Mineralization

ABSTRACT Dentin hypersensitivity is commonly managed by surface‐based tubule occlusion strategies that rely on abrupt mineral precipitation, yet such approaches poorly replicate the graded hard‐soft interfaces that confer mechanical resilience to native dentin. Here, inspired by the hierarchical organization of the dentin mineralization front, we report a biomimetic strategy to reconstruct a graded mineral‐collagen interface on demineralized dentin through protein‐mediated mineralization. Histological and nanomechanical analyses of native dentin reveal a wave‐like transition zone composed of mesoscale mineralized spherules (MSs), coincident with a gradual modulus transition across the hard‐soft boundary. To emulate this architecture, a phosphorylated protein analogue, phosvitin grafted with polyethylene glycol (PV‐PEG), is used to stabilize mineral precursors and guide the nanoscale cross‐fibrillar mineralization that constructed into a continuous MS layer on demineralized dentin. The resulting MS layer serves as a stress buffer zone, facilitating stress redistribution. In vitro and in vivo evaluations demonstrate effective tubule occlusion, recovery of mechanical properties, favorable biocompatibility, and enhanced odontogenic differentiation in pulp‐derived cells. These findings establish a protein‐guided approach for reconstructing a hierarchical mineral‐collagen interface on dentin and define a materials framework for graded interface design relevant to durable dentin repair, with dentin hypersensitivity as a motivating application.