Silk Fibroin-Based Hydrogel Desensitizer Achieving 660 μm Dentin Tubule Occlusion for Dentin Hypersensitivity Treatment

Abstract

Dentin hypersensitivity (DH) causes sharp pain due to external stimuli transmitted through narrow dentinal tubules (DTs) in exposed dentin. Current desensitizers struggle to provide sufficient DT occlusion depth and density, limiting long-term effectiveness under daily erosion and friction. Inspired by fish schooling behavior, we introduce an adaptive hydrogel desensitizer (STU) composed of “sardines” (tannic acid and silk fibroin) and “predators” (urea). The “sardines” form a tightly packed hydrogel "shoal" through hydrogen bonds, while the “predators” disrupt these bonds, transforming STU into a fluid form that quickly infiltrates DTs upon application. As urea diffuses in saliva, hydrogen bonds rapidly re-form, reassembling the hydrogel “shoal” to securely bond DT walls and achieve stable, dense occlusion up to 660 μm deep -- approximately 3 times greater than the current best. This occlusion remains effective under extended in vitro and in vivo erosion and friction, restoring dentin hardness to healthy levels without noticeable mucosal damage in the rat cavity. Deep occlusion and biocompatibility were further validated in a rabbit model with significantly smaller DTs. Along with its long shelf life (> 10 m in dehydrated form) and ease of application, this natural desensitizer offers a promising clinical solution for instant, permanent relief from DH.