This aim of this review is to explore the current research related to crosslinking agents used on dentine. A systematic search of publications in PubMed and Web of Science databases was performed. Further retrieval was conducted using the search terms of specific names of crosslinkers. Reviews, conference abstracts, dissertation and theses, non-English articles, studies of intrinsic crosslinking of dentine, studies of adhesives without specific crosslinker components, studies of crosslinker applications in other collagenous tissues or tooth-like structures and irrelevant studies were excluded. Manual screening was conducted on the bibliographies of remaining papers to identify other relevant articles. One hundred and one articles were included in this systematic review and full texts were retrieved. Both synthetic and naturally derived crosslinkers have been found to exhibit significant effects in biomodification of dentine via their multiple interactions with the dentine matrix. A stable matrix network or a durable hybrid layer in dentine bonding could be achieved, where the dentine collagen fibrils show improved biochemical and biomechanical properties and enzymatic biodegradation is reduced. Although no crosslinkers have been tested in clinical trials, extensive research has been conducted in laboratory studies to investigate their potential applicability for inhibition of demineralisation and/or promotion of remineralisation, caries prevention as well as improvement of bonding performance of adhesive systems. Further studies are needed to develop the feasibility for clinical use, reduce side effects as well as explore mechanisms of action and long-term effectiveness.
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