A Drop‐By‐Drop Self‐Assembled All‐Natural Hydrogel as a Desensitizer for Rapid and Enduring Management of Dentin Hypersensitivity

Abstract Dentin hypersensitivity (DH) is a prevalent dental condition arising from the exposure of dentin tubules (DTs), leading to discomfort upon external stimuli. However, achieving swift and profound occlusion of these exposed DTs for immediate and enduring relief remains challenging due to the intricate dentin structure and oral environment. Herein, a pioneering and facile drop‐by‐drop strategy involving an in situ generated natural supramolecular hydrogel formed by self‐assembling silk fibroin (SF) and tannic acid (TA) within the narrow DT space is proposed. When SF and TA aqueous solutions are applied successively to exposed dentin, they penetrate deeply within DTs and coassemble into compact gels, robustly adhering to DT walls. This yields a rapid and compact occlusion effect with an unprecedented depth exceeding 250 µm, maintaining stable occlusion efficacy even under rigorous in vitro and in vivo erosion and friction conditions for no less than 21 days. Furthermore, the biocompatibility and effective occlusion properties are verified through cell studies in simulated oral settings and an in vivo rabbit model. This study, for the first time, demonstrates the translational potential of hydrogel‐based desensitizers in treating DH with prompt action, superior occlusion depth and enduring treatment benefits, holding promise as clinical‐friendly restorative solutions for delicate‐structured biosystems.