Objective The objective was to examine the effect of a solvent dimethyl sulfoxide (DMSO) on resin-dentin bond durability, as well as potential functional mechanisms behind the effect. Methods Microtensile bond strength (μTBS) was evaluated in extracted human teeth in two separate experiments. Dentin specimens were acid-etched and assigned to pre-treatment with 0.5 mM (0.004%) DMSO as additional primer for 30 s and to controls with water pre-treatment. Two-step etch-and-rinse adhesive (Scotchbond 1XT, 3M ESPE) was applied and resin composite build-ups were created. Specimens were immediately tested for μTBS or stored in artificial saliva for 6 and 12 months prior to testing. Additional immediate and 6-month specimens were examined for interfacial nanoleakage analysis under SEM. Matrix metalloproteinase (MMP) inhibition by DMSO was examined with gelatin zymography. Demineralized dentin disks were incubated in 100% DMSO to observe the optical clearing effect. Results The use of 0.5 mM DMSO had no effect on immediate bond strength or nanoleakage. In controls, μTBS decreased significantly after storage, but increased significantly in DMSO-treated group. The control group had significantly lower μTBS than DMSO-group after 6 and 12 months. DMSO also eliminated the increase in nanoleakage seen in controls. 5% and higher DMSO concentrations significantly inhibited the gelatinases. DMSO induced optical clearing effect demonstrating collagen dissociation. Significance DMSO as a solvent may be useful in improving the preservation of long-term dentin-adhesive bond strength. The effect may relate to dentinal enzyme inhibition or improved wetting of collagen by adhesives. The collagen dissociation required much higher DMSO concentrations than the 0.5 mM DMSO used for bonding. © 2013 Academy of Dental Materials.291010551062Pashley, D.H., Tay, F.R., Breschi, L., Tjäderhane, L., Carvalho, R.M., Carrilho, M., State of the art etch-and-rinse adhesives (2011) Dental Materials, 27, pp. 1-16De Munck, J., Mine, A., Poitevin, A., Van Ende, A., Cardoso, M.V., Van Landuyt, K.L., Meta-analytical review of parameters involved in dentin bonding (2012) Journal of Dental Research, 91, pp. 351-357Tjäderhane, L., Nascimento, F.D., Breschi, L., Mazzoni, A., Tersariol, I.L.S., Geraldeli, S., Optimizing dentin bond durability: Control of collagen degradation by matrix metalloproteinases and cysteine cathepsins (2013) Dental Materials, 29, pp. 116-135Marren, K., Dimethyl sulfoxide: An effective penetration enhancer for topical administration of NSAIDs (2011) The Physician and Sportsmedicine, 39, pp. 75-82Yeh, A.T., Choi, B., Nelson, J.S., Tromberg, B.J., Reversible dissociation of collagen in tissues (2003) Journal of Investigative Dermatology, 121, pp. 1332-1335Zimmerley, M., McClure, R.A., Choi, B., Potma, E.O., Following dimethyl sulfoxide skin optical clearing dynamics with quantitative nonlinear multimodal microscopy (2009) Applied Optics, 48, pp. 79-D87Vishnyakov, A., Lyubartsev, A.P., Laaksonen, A., Molecular dynamics simulations of dimethyl sulfoxide and dimethyl sulfoxide-water mixture (2001) The Journal of Physical Chemistry A, 105, pp. 1702-1710Geurtsen, W., Lehmann, F., Spahl, W., Leyhausen, G., Cytotoxicity of 35 dental resin composite monomers/additives in permanent 3T3 and three human primary fibroblast cultures (1998) Journal of Biomedical Materials Research, 41, pp. 474-480Thonemann, B., Schmalz, G., Hiller, K.A., Schweikl, H., Responses of L929 mouse fibroblasts, primary and immortalized bovine dental papilla-derived cell lines to dental resin components (2002) Dental Materials, 18, pp. 318-323Xu, X., Wang, Y., Lauer-Fields, J.L., Fields, G.B., Steffensen, B., Contributions of the MMP-2 collagen binding domain to gelatin cleavage. Substrate binding via the collagen binding domain is required for hydrolysis of gelatin but not short peptides (2004) Matrix Biology, 23, pp. 171-181Carrilho, M.R., Carvalho, R.M., De Goes, M.F., Di Hipólito, V., Geraldeli, S., Tay, F.R., Chlorhexidine preserves dentin bond in vitro (2007) Journal of Dental Research, 86, pp. 90-94Carrilho, M.R., Geraldeli, S., Tay, F., De Goes, M.F., Carvalho, R.M., Tjäderhane, L., In vivo preservation of the hybrid layer by chlorhexidine (2007) Journal of Dental Research, 86, pp. 529-533Klein-Júnior, C.A., Zander-Grande, C., Amaral, R., Stanislawczuk, R., Garcia, E.J., Baumhardt-Neto, R., Evaporating solvents with a warm air-stream: Effects on adhesive layer properties and resin-dentin bond strengths (2008) Journal of Dentistry, 36, pp. 618-625Kato, M.T., Leite, A.L., Hannas, A.R., Oliveira, R.C., Pereira, J.C., Tjäderhane, L., Effect of iron on matrix metalloproteinase inhibition and on the prevention of dentine erosion (2010) Caries Research, 44, pp. 309-316Bui, A.K., McClure, R.A., Chang, J., Stoianovici, C., Hirshburg, J., Yeh, A.T., Revisiting optical clearing with dimethyl sulfoxide (DMSO) (2009) Lasers in Surgery and Medicine, 41, pp. 142-148Steffensen, B., Wallon, U.M., Overall, C.M., Extracellular matrix binding properties of recombinant fibronectin type II-like modules of human 72-kDa gelatinase/type IV collagenase. High affinity binding to native type i collagen but not native type IV collagen (1995) Journal of Biological Chemistry, 270, pp. 11555-11566Kupai, K., Szucs, G., Cseh, S., Hajdu, I., Csonka, C., Csont, T., Matrix metalloproteinase activity assays: Importance of zymography (2010) Journal of Pharmacological Methods, 61, pp. 205-209Toth, M., Sohail, A., Fridman, R., Assessment of gelatinases (MMP-2 and MMP-9) by gelatin zymography (2012) Methods in Molecular Biology, 878, pp. 121-135Vargas, G., Chan, E.K., Barton, J.K., Rylander III, H.G., Welch, A.J., Use of an agent to reduce scattering in skin (1999) Lasers in Surgery and Medicine, 24, pp. 133-141Hirshburg, J., Choi, B., Nelson, J.S., Yeh, A.T., Collagen solubility correlates with skin optical clearing (2006) Journal of Biomedical Optics, 11, pp. 0405011-405013Walton, R.E., Outhwaite, W.C., Pashley, D.P., Magnification - An interesting optical property of dentin (1976) Journal of Dental Research, 55, pp. 639-642Kienle, A., Michels, R., Hibst, R., Magnification - A new look at a long-known optical property of dentin (2006) Journal of Dental Research, 85, pp. 955-959Liu, K., Cruzan, J.D., Saykally, R.J., Water clusters (1996) Science, 271, pp. 929-933Gregory, J.K., Clary, D.C., Liu, K., Brown, M.G., Saykally, R.J., The water dipole moment in water clusters (1997) Science, 275, pp. 814-817Luzar, A., Chandler, D., Structure and hydrogen bond dynamics of water-dimethyl sulfoxide mixtures by computer simulations (1993) Journal of Chemical Physics, 98, pp. 8160-8173Venkataramanan, N.S., Microsolvation of DMSO: Density functional study on the structure and polaraizabilities (2012) International Journal of Quantum Chemistry, 112, pp. 2599-2606Catalán, J., Díaz, C., García-Blanco, F., Characterization of binary solvent mixtures of DMSO with water and other cosolvents (2001) Journal of Organic Chemistry, 66, pp. 5846-5852Vaisman, I.I., Berkowitz, M.L., Local structural order and molecular associations in water-DMSO mixtures. Molecular dynamics study (1992) Journal of the American Chemical Society, 114, pp. 1889-1896Mehtälä, P., Agee, K., Breschi, L., Pashley, D.H., Tjäderhane, L., Proprietary solvent enhances dentin wettability (2010) Dental Materials, 26 (SUPPL. 1), pp. 12-e13. , [Abstr. No. 25]Hirshburg, J.M., Ravikumar, K.M., Hwang, W., Yeh, A.T., Molecular basis for optical clearing of collagenous tissues (2010) Journal of Biomedical Optics, 15, pp. 055002-55011Bertassoni, L.E., Orgel, J.P., Antipova, O., Swain, M.V., The dentin organic matrix - Limitations of restorative dentistry hidden on the nanometer scale (2012) Acta Biomaterialia, 8, pp. 2419-2433Sea, J., Teichman, J.M., Paediatric painful bladder syndrome/interstitial cystitis: Diagnosis and treatment (2009) Drugs, 69, pp. 279-296Bianchi, L., Carrilho, M., Tjäderhane, L., De Souza Costa, C.A., Hebling, J., Cytotoxicity of different concentrations of dimethyl sulfoxide on odontoblast-like cells (2012) Journal of Dental Research, 91 (SPEC ISS B). , http://www.dentalresearch.org/, Abstr. 1700 ()Bianchi, L., Basso, F.G., Carrilho, M.R.O., Tjäderhane, L., De Souza Costa, C.A., Hebling, J., Effects of dimethyl sulfoxide (DMSO) on odontoblast-like cells activity (2012) Dental Materials, 28 (SUPPL. 1), p. 4. , [Abstr. No. 7]Schweikl, H., Spagnuolo, G., Schmalz, G., Genetic and cellular toxicology of dental resin monomers (2006) Journal of Dental Research, 85, pp. 870-877Goldberg, M., In vitro and in vivo studies on the toxicity of dental resin components: A review (2008) Clinical Oral Investigations, 12, pp. 1-8Lanza, C.R., De Souza Costa, C.A., Furlan, M., Alécio, A., Hebling, J., Transdentinal diffusion and cytotoxicity of self-etching adhesive systems (2009) Cell Biology and Toxicology, 25, pp. 533-543Harpham, M.R., Levinger, N.E., Ladanyi, B.M., An investigation of water dynamics in binary mixtures of water and dimethyl sulfoxide (2008) Journal of Physical Chemistry B, 112, pp. 283-293