Crosslinking Improve Demineralized Dentin Performance and Synergistically Promote Biomimetic Mineralization by CaP_PILP

[Image: see text] Objective: to explore the effects of optimal crosslinking (chemical treatment) on demineralized dentin matrix and the possible synergism with calcium phosphate polymer-induced liquid precursor (CaP-PILP) bionic remineralization (physical treatment), and offer benefit to the clinic of resin–dentin bonding and dentin hypersensitivity. Methods: demineralized dentin was treated with glutaraldehyde (GA), carbodiimide (EDC), and procyanidin (PA) for crosslinking, followed by CaP-PILP biomimetic remineralization. The morphology, surface mechanical and physio-chemical properties, and enzymatic resistance were evaluated regardless of the modification. Results: the collagen fibers appeared morphologically complete with higher surface microhardness and characteristic peaks of amide I–III bands were visible after GA, PA, and EDC crosslinking. Collagen collapse and dissolution were seen in untreated demineralized dentin with enzyme attack, while the collagen fiber structure remained intact in GA- and PA-treated specimens. The lamellar mineral phase was visible at 2 days and the dentin tubules were almost completely enclosed at 4–6 days after PA crosslinking and mineralization. However, demineralized collagen fibers and open tubules were still visible between the dentinal tubules on day 8 in the control group. Conclusion: the structure integrity, enzyme resistance, and mechanical properties of the collagen fiber network could be significantly preserved by GA and PA crosslinking than EDC and no treatment. While, strongest synergistic effects were observed in PA on bionic remineralization by CaP-PILP, and further significantly improve the quality and shorten the duration of mineralization. These findings would be beneficial for dental clinical practice of resin–dentin bonding and dentin hypersensitivity.