Objectives The biomodification of dentin is a biomimetic approach, mediated by bioactive agents, to enhance and reinforce the dentin by locally altering the biochemistry and biomechanical properties. This review provides an overview of key dentin matrix components, targeting effects of biomodification strategies, the chemistry of renewable natural sources, and current research on their potential clinical applications. Methods The PubMed database and collected literature were used as a resource for peer-reviewed articles to highlight the topics of dentin hierarchical structure, biomodification agents, and laboratorial investigations of their clinical applications. In addition, new data is presented on laboratorial methods for the standardization of proanthocyanidin-rich preparations as a renewable source of plant-derived biomodification agents. Results Biomodification agents can be categorized as physical methods and chemical agents. Synthetic and naturally occurring chemical strategies present distinctive mechanism of interaction with the tissue. Initially thought to be driven only by inter- or intra-molecular collagen induced non-enzymatic collagen cross-linking, multiple interactions with other dentin components are fundamental for the long-term biomechanics and biostability of the tissue. Oligomeric proanthocyanidins show promising bioactivity, and their chemical complexity requires systematic evaluation of the active compounds to produce a fully standardized intervention material from renewable resource, prior to their detailed clinical evaluation. Significance Understanding the hierarchical structure of dentin and the targeting effect of the bioactive compounds will establish their use in both dentin-biomaterials interface and caries management.

Objectives-To characterize the properties of dentin matrix treated with two proanthocyanidin rich cross-linking agents and their effect on dentin bonded interfaces.Methods-Sound human molars were cut into 0.5 mm thick dentin slabs, demineralized and either treated with one of two cross-linking agents (grape seed -GSE and cocoa seed -COE extracts) or left untreated. The modulus of elasticity of demineralized dentin was assessed after 10 or 60 min and the swelling ratio after 60 min treatment. Bacterial collagenase was also used to assess resistance to enzymatic degradation of samples subjected to ultimate tensile strength. The effect of GSE or COE on the resin-dentin bond strength was evaluated after 10 or 60 min of exposure time. Data were statistically analyzed at a 95% confidence interval.Results-Both cross-linkers increased the elastic modulus of demineralized dentin as exposure time increased. Swelling ratio was lower for treated samples when compared to control groups. No statistically significant changes to the UTS indicate that collagenase had no effect on dentin matrix treated with either GSE or COE. Dentin-resin bonds significantly increased following treatment with GSE regardless of the application time or adhesive system used.Significance-Increased mechanical properties and stability of dentin matrix can be achieved by the use of PA-rich collagen cross-linkers most likely due to the formation of a PA-collagen complex. The short term dentin-resin bonds can be improved after 10 minutes dentin treatment.

Objectives To characterize the interaction of 1-Ethyl-3-[3-dimethylaminopropyl] carbodiimide Hydrochloride (EDC) with dentin matrix and its effect on the resin-dentin bond. Methods Changes to the stiffness of demineralized dentin fragments treated with EDC/N-hydroxysuccinimide (NHS) in different solutions were evaluated at different time points. The resistance against enzymatic degradation was indirectly evaluated by ultimate tensile strength (UTS) test of demineralized dentin treated or not with EDC/NHS and subjected to collagenase digestion. Short- and long-term evaluations of the strength of resin-dentin interfaces treated with EDC/NHS for 1 hour were performed using microtensile bond strength (µTBS) test. All data (MPa) were individually analyzed using ANOVA and Tukey HSD tests (α=0.05). Results The different exposure times significantly increased the stiffness of dentin (p<0.0001, control - 5.15 and EDC/NHS - 29.50), while no differences were observed among the different solutions of EDC/NHS (p=0.063). Collagenase challenge did not affect the UTS values of EDC/NHS group (6.08) (p>0.05), while complete degradation was observed for the control group (p=0.0008, control - 20.84 and EDC/NHS - 43.15). EDC/NHS treatment did not significantly increase resin-dentin µTBS, but the values remained stable after 12 months water storage (p<0.05). Conclusions Biomimetic use of EDC/NHS to induce exogenous collagen cross-links resulted in increased mechanical properties and stability of dentin matrix and dentin-resin interfaces.