Application strategies for dentin cross-linking agents during adhesive restorative procedures: a scoping review protocol.

This study is a scoping review aimed at mapping and systematizing available evidence regarding strategies for applying dentin cross-linking agents during adhesive restorative procedures. The relevance of this research lies in the need to better understand the factors influencing the durability of the adhesive interface, given that its degradation—mediated primarily by proteolytic enzymes such as matrix metalloproteinases (MMPs) and cysteine ​​cathepsins—is a major cause of adhesive restoration failure. In this context, various approaches have been proposed in the literature to enhance the stability of the dentin collagen matrix, including the use of enzyme inhibitors and cross-linking agents capable of cross-linking collagen fibers and increasing resistance to degradation. However, there is substantial variability among experimental protocols regarding the types of agents, concentrations, application times, application methods, and stages of incorporation into restorative procedures. This heterogeneity complicates the consolidation of evidence and the establishment of standardized clinical protocols. Therefore, this study aims to identify and describe the protocols and formulations used for applying dentin cross-linking agents in *in vitro* laboratory studies, as well as to analyze their effects on inhibiting proteolytic enzymes and stabilizing collagen fibers. Additionally, the study seeks to characterize key outcomes evaluated, such as bond strength and adhesive interface durability. This scoping review will be conducted in accordance with the methodological recommendations of the Joanna Briggs Institute (JBI) and reported following the PRISMA-ScR checklist. A comprehensive search will be performed across multiple databases, including PubMed/MEDLINE, Scopus, Web of Science, Embase, SciELO, LILACS, and Google Scholar. Only *in vitro* laboratory studies using human teeth and evaluating dentin cross-linking agents and/or enzyme inhibitors in the context of adhesive restoration will be included, provided they clearly describe the protocols employed. Extracted data will be organized descriptively and analyzed via a narrative synthesis, allowing studies to be grouped according to the agents used and their respective application strategies. Additionally, a bibliometric analysis will be conducted to identify publication patterns and research trends in the field. The expected results of this study include providing a comprehensive overview of the current state of the literature—highlighting the most investigated protocols, their strengths and limitations, and identifying existing scientific gaps, particularly regarding methodological standardization and the lack of clinical evidence. Ultimately, this study aims to support future lines of research and contribute to the development of strategies that enhance the longevity of the adhesive interface in restorative dentistry.