Resveratrol-Cucurbituril Complex Boosts Tooth Remineralization Without Toxicity

Dental bonding durability is a long-standing clinical challenge. When dentin is prepared for bonding, collagen fibers in deeper layers become exposed and vulnerable to enzymatic degradation by matrix metalloproteinases (MMPs). Simultaneously, demineralized zones can form that weaken the bond interface over time. Addressing both problems simultaneously — promoting remineralization and inhibiting MMPs — has been difficult without causing cellular toxicity.

Resveratrol, a well-studied natural polyphenol found in grapes and red wine, has shown promise in inhibiting MMPs and supporting dentin remineralization. However, its benefits are concentration dependent, and higher effective doses introduce cytotoxicity, limiting clinical utility. To resolve this, the research team encapsulated resveratrol within cucurbit[n]uril molecular cages (specifically Q[6] and Q[7]), forming Res@Q[n] complexes designed for controlled, sustained release.

The complexes were characterized using analytical chemistry and quantum chemical analysis. In laboratory experiments, Res@Q[n] released resveratrol steadily over nearly a month. Compared to free resveratrol, the complexes demonstrated stronger MMP-9 inhibition, more pronounced remineralization of both recombinant type I collagen and actual dentin samples, and significantly improved microtensile bond strength. Nanoleakage — a marker of bond interface degradation — was also substantially reduced, even after aging stress tests.

Critically, the complexes achieved these outcomes without the cytotoxicity associated with high-dose free resveratrol, suggesting the encapsulation approach modulates bioavailability in a clinically favorable way.

Implications extend beyond dentistry. Controlled delivery of polyphenols like resveratrol via supramolecular chemistry could inform strategies in tissue regeneration and anti-aging applications where sustained low-level polyphenol exposure is desirable. Caveats include the study's in vitro nature and limited translation data for clinical dental bonding protocols.