Biofunctional modulation of the resin–dentin interface by zinc-containing adhesive systems: A systematic review of matrix metalloproteinase inhibition and hybrid layer stability

This systematic review aimed to evaluate whether zinc-containing adhesive systems and adhesive-related zinc-based modification strategies can reduce proteolytic/MMP-related activity and preserve hybrid layer stability at the resin–dentin interface. A comprehensive literature search was conducted in PubMed/MEDLINE, Scopus, Embase, Web of Science Core Collection, and the Cochrane Library. Eligible studies included in vitro, ex vivo, translational, and clinical investigations assessing zinc-containing formulations in comparison with unmodified adhesive systems or control conditions, with outcomes related to proteolytic activity, collagen degradation, bond strength, nanoleakage, or interfacial preservation. Of 75 identified records, 9 studies met the inclusion criteria for qualitative synthesis. Most studies showed a moderate risk-of-bias profile, with more recent investigations demonstrating improved methodological transparency. Overall, zinc-containing strategies were associated with reduced proteolytic activity, lower nanoleakage, and preservation of immediate bond strength, while some formulations also showed improved durability after aging or cariogenic challenge. However, these effects were heterogeneous across materials and experimental models, and the strongest evidence supported collagen-protective and interfacial-stabilizing effects rather than a consistent direct inhibition of MMP activity. Due to substantial heterogeneity in zinc delivery systems, adhesive formulations, aging protocols, and analytical methods, meta-analysis was not considered appropriate. The available evidence suggests that zinc-containing strategies may represent a promising biofunctional approach for enhancing resin–dentin interface stability, although the certainty of evidence remains low to very low in most outcome domains.