A Bioinspired Approach to Mechanically Reinforce Collagen‐Rich Tissues Using Modularly Defined Stilbenoids

Natural products, particularly plant-derived compounds, have long inspired the development of novel dental biomaterials. This study explored the modularity and bioactivity of natural stilbenoids as dental tissue biomodulators, focusing on their ability to reinforce dentin mechanically through interactions with type I collagen. Mid-coronal dentin specimens from human molars were demineralized and treated with 1% solutions of modularly defined stilbenoids (MoDS): a monomer (resveratrol), dimers (ε-viniferin, ampelopsin A), and tetramers (vitisin A, vitisin B). Dynamic mechanical analysis (DMA) assessed viscoelastic properties (E', E″, E*, tan δ) over 6 months, while Fourier-transform infrared spectroscopy (FTIR) evaluated biochemical changes, and cell viability assays determined biocompatibility. Statistical analysis used ANOVA with post hoc tests (α = 0.05). Only oligomeric MoDS significantly enhanced dentin viscoelasticity (p < 0.001), with vitisin B showing the highest fold increase in E* modulus (17-fold), followed by vitisin A and ε-viniferin. FTIR confirmed permanent collagen modifications in oligomer-treated groups, while resveratrol showed no mechanical effect. MoDS-induced changes stabilized over time, and all compounds exhibited high biocompatibility, with vitisin B maintaining the highest cell viability. These results demonstrate that MoDS improve dentin mechanical properties and stability through structure-dependent cross-linking, highlighting their potential for durable, bioinspired dental restorations.