Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)This study evaluated a new approach, named dimethyl sulfoxide (DMSO)-wet bonding, to produce more desirable long-term prospects for the ultrafine interactions between synthetic polymeric biomaterials and the inherently hydrated dentin substrate. Methods. Sound third molars were randomly restored with/without DMSO pretreatment using a total-etch (Scocthbond Multipurpose: SBMP) and a self-etch (Clearfil SE Bond: CF) adhesive systems. Restored teeth (n = 10)/group were sectioned into sticks and submitted to different analyses: micro-Raman determined the degree of conversion inside the hybrid layer (DC); resin dentin microtensile bond strength and fracture pattern analysis at 24 h, 1 year and 2 years of aging; and nanoleakage evaluation at 24h and 2 years. Results. DMSO-wet bonding produced significantly higher 24 h bond strengths for SBMP that were sustained over the two-year period, with significantly less adhesive failures. Similarly, DMSO-treated CF samples presented significantly higher bond strength than untreated samples at two years. Both adhesives had significant less adhesive failures at 2 years with DMSO. DMSO had no effect on DC of SBMP, but significantly increased the DC of CE DMSO-treated SBMP samples presented reduced silver uptake compared to untreated samples after aging. Significance. Biomodification of the dentin substrate by the proposed strategy using DMSO is a suitable approach to produce more durable hybrid layers with superior ability to withstand hydrolytic degradation over time. Although the active role of DMSO on dentin bond improvement may vary according to monomer composition, its use seems to be effective on both self-etch and etch-and-rinse bonding mechanisms. (C) 2016 The Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.321214721481CAPESCNPqAcademy of FinlandCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)