occluding resins, dentin adhesives, [3] mineral nanoparticles, or remineralization coatings, such as commercially available Green Or, Hybrid Coat, Gluma Desensitizer, and Duraphat, as well as polyphenol-based coatings, have been proposed for DH treatment. [4][5][6] Unfortunately, the majority of existing desensitizers fail to obtain satisfactory results for treating DH because they only seal orifices within 10 Âľm of DTs instead of a deep occlusion, and these sealers tend to peel off due to mechanical friction (such as tooth brushing). With the mineralizing adhesives as example, they typically seal the dentin surface instead of in-depth of DTs. Moreover, the leaching of unpolymerized monomers from adhesives has been implicated in hypersensitivity, cytotoxicity, genotoxicity, estrogenicity, and alteration of immune responses. [7] On the other hand, the antifouling property has been ignored for a long time in existing desensitizing products, and as a result, oral bacteria easily adhere onto the salivary acquired pellicle (SAP)-coated mineral layer to form a biofilm, [8] which produce toxins and even cause chronic diseases such as pulpitis. To overcome the drawbacks of current products, developing a rapid and convenient occlusion technique in deep DTs combining antifouling and easy remineralization is necessary but challenging to treat DH with long-term curing stability.Recently, our work demonstrated that lysozyme could undergo a fast amyloid-like aggregation in physiological conditions through the rapid reduction of its intramolecular disulfide bonds by tris(2-carboxyethyl)phosphine (TCEP). [9] In this process, the high-energy Îą-helix structure of native lysozyme is unfolded and aggregates into β-sheet stacking-based oligomers. A protein nanofilm, also called phase-transitioned lysozyme (PTL), is then formed in â2 h through the agglomeration of the oligomers at the liquid/solid interface, offering a robust, multifunctional, biocompatible and colorless transparent coating on flat or porous macroscopic substrates as well as micro/nanoparticles. [10,11] In the present study, we report a greatly deep occlusion of DTs by coating DTs with antifouling amyloid-like lysozyme oligomer aggregates and occluding with in situ formation of a biomimetic hydroxyapatite (HAp) layer on the coating. We demonstrate that the oligomer species, Exposure of dentinal tubules (DTs) leads to the transmission of external stimuli within the DTs, causing dental hypersensitivity (DH). To treat DH, various desensitizers have been developed for occluding DTs. However, most desensitizers commercially available or in development are only able to seal the orifices, rather than the deep regions of the DTs, thus lacking long-term stability. Herein, it is shown that the fast amyloid-like aggregation of lysozyme (lyso) conjugated with poly(ethylene glycol) (PEG) (lyso-PEG) can afford a robust ultrathin nanofilm on the deep walls of DTs through a rapid one-step aqueous coating process (in 2 min). The resultant nanofilm provides a highly effective antifoul...