Dentin Collagen Crosslinking for Enhanced Resin–Dentin Bond Longevity: Evidence and Clinical Perspectives

Abstract The durability of the dentin–resin bonded interface remains a major challenge in adhesive dentistry, largely due to hydrolytic and enzymatic degradation of exposed collagen fibrils within the hybrid layer. Endogenous proteolytic enzymes, particularly matrix metalloproteinases and cysteine cathepsins, play a critical role in the progressive degradation of the exposed collagen matrix. Collagen crosslinking has emerged as a promising strategy to stabilize the dentin matrix, enhance resistance to endogenous proteases, and potentially improve the long-term durability of adhesive bonds; however, current evidence remains largely experimental, and its routine clinical application is still limited. This narrative review synthesizes current preclinical and emerging translational evidence on collagen crosslinking approaches investigated to reinforce the dentin–resin interface and the characterization techniques used to evaluate their effectiveness. Emphasis is placed on mechanisms of action, key evaluation approaches, and potential clinical relevance. While several crosslinking strategies, particularly carbodiimide-based systems and polyphenol-derived agents, demonstrate encouraging in vitro and laboratory-based outcomes, significant barriers to routine clinical translation persist. These include application time, penetration depth, esthetic concerns, biocompatibility, and integration within existing clinical adhesive workflows. Future research should prioritize clinically feasible formulations, standardized testing protocols, and long-term in vivo and clinical validation to facilitate the potential translation of collagen crosslinking strategies into clinically durable adhesive restorations.