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

## TL;DR

This study shows that certain plant compounds can strengthen tooth dentin by improving its mechanical properties and stability, offering a promising approach for dental restorations.

## Contribution

The study introduces modularly defined stilbenoids as effective, structure-dependent biomodulators for mechanically reinforcing collagen-rich dental tissues.

## Key findings

- Oligomeric stilbenoids significantly enhanced dentin viscoelasticity, with vitisin B showing the highest improvement.
- FTIR confirmed permanent collagen modifications in oligomer-treated groups, indicating structural cross-linking.
- All tested stilbenoids exhibited high biocompatibility, with vitisin B maintaining the highest cell viability.

## Abstract

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.

A schematic diagram of dentin biomodification using modularly defined stilbenoids (MoDS). Stilbenoids interact with type I collagen at multiple hierarchical levels, inducing intermolecular and inter‐microfibrillar cross‐linking that enhances dentin viscoelastic properties, structural stability, and biocompatibility.