A Novel Multi-Cross-linking Diluent System to Stabilize Self-Etch Bonding

Despite the indispensability of 2-hydroxyethyl methacrylate (HEMA) for improving the wettability of self-etch (SE) adhesives, elevated concentration may compromise the durability of the hybrid layer. This study proposes a modification strategy to preserve the wettability of SE adhesives while reducing excessive HEMA content and enhancing hybrid layer integrity through introducing collagen-protective and hydrophobic features. Thus, a novel diluent system was developed by partially replacing HEMA with 2 hydrophobic cross-linking reagents, 3-(4-formylphenoxy)-2-hydroxypropyl methacrylate (FPA) and glycidyl methacrylate (GMA). Attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR), confocal laser scanning microscopy (CLSM), wettability, and water contact angle analyses confirmed that FPA induced rapid but transient cross-linking with collagen. Thus, the compatibility of collagen with hydrophobic adhesives was improved. The time-dependent cross-linking efficacy of GMA was evaluated by ATR-FTIR and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Guided by these findings, FPA-GMA adhesives were formulated and subjected to physicochemical (flexural strength, Vickers microhardness, and water sorption/solubility) and biological (Cell Counting Kit-8, calcein acetoxymethyl ester/propidium iodide) evaluations. Enzymatic degradation assays, including in situ zymography, gelatin zymography, and the hydroxyproline releasing test, verified that FPA-GMA adhesives built the degradation-resistant hybrid layer during dentin bonding. CLSM, micro-tensile bond strength, and nanoleakage analysis corroborated the establishment of a stable and durable FPA-GMA dentin-bonding interface before and after 10,000 thermocycles. Collectively, this study evaluated whether FPA-GMA formulations improve the physicochemical properties of experimental adhesives and their biological/functional interactions with dentin, as assessed by enzymatic activity and bonding performance at the dentin-bonding interface. The results demonstrated that FPA-GMA provided sustained collagen protection while preserving SE infiltration and enhancing its mechanical properties, which thereby improved the durability of the dentin-bonding interface.