Improvement of dentin bonding via adhesive monomers with multiple hydrogen bonding moieties

Despite advancements in bonding techniques, the resin-dentin interface remains the weakest point in dental restorations, susceptible to collagen degradation and methacrylate hydrolysis. One strategy to enhance the resin-dentin interface is to incorporate hydrogen-bonding-rich functional groups into dental adhesive resins, such as 2-ureido-4[1H]-pyrimidinone (UPy). These hydrogen bonds may bridge the adhesive resin and dentin substrate, which contains collagen and hydroxyapatite, as well as form non-covalent crosslinks within the resin. Here, we utilize UPy-functionalized methacrylamides modified with glycol spacers to ensure compatibility with other monomers commonly used in adhesive resins, as well as to promote hydrogen bonding at the resin-dentin interface and within the bulk resin. Three UPy-based methacrylamides: UPy-OPG400-MMA, UPy-OPG230-MMA and UPy-OEG148-MMA were synthesized and incorporated into model methacrylate-based adhesive formulations. Results show that the UPy-methacrylamides enhance polymerization kinetics, biocompatibility, and mechanical performance. However, these improvements and the efficacy of hydrogen-bond formation depend on the flexibility of the glycol spacers. Specifically, resins containing UPy-OPG230-MMA have the most robust hydrogen bonding in aqueous conditions, making them the optimal choice in this study. This selection is further confirmed by micro-tensile bonding strength (μTBS) analysis and interfacial characterizations, which shows a significant enhancement in bonding performance when 50 wt% of 2-hydroxyethyl methacrylate (HEMA) is replaced with UPy-OPG230-MMA in a model self-etch adhesive. Overall, this work presents a strategy to enhance dental adhesive performance by incorporating hydrogen-bonding motifs that reinforce both the polymer network and the resin-dentin interface, offering improved durability under clinically relevant conditions. Statement of Significance: This study shows that hydrogen bonding interactions improve the overall performance of dental adhesives. Adhesive monomers with the 2-ureido-4[1H]-pyrmidinone (UPy) group facilitate significant hydrogen bonding interactions both within the adhesive as well as between the adhesive and an external substrate (here, dentin). This results in improved mechanical integrity of the adhesive (e.g. strength and integrity of the bonding) and impacts critical biomaterial properties such as biocompatibility. This work is significant as prior demonstrations utilizing UPy functionalities for enhanced adhesion require organic solvents (e.g. DMSO) that are incompatible with in situ, dental materials applications. Here we synthesize UPy-functionalized monomers that are miscible in aqueous solvents (water, ethanol) and compatible with comonomers used in dental materials applications.