Fu Denghao, Hardy Jonathan, Szczepanski Caroline R
Department of Chemical Engineering & Materials Science, Michigan State University, East Lansing, MI 48824, USA.
Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI 48824, USA.
Acta Biomater. 2025 Sep 2. doi: 10.1016/j.actbio.2025.08.052.
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.
尽管粘结技术取得了进步，但树脂 - 牙本质界面仍然是牙科修复体中最薄弱的环节，易受胶原蛋白降解和甲基丙烯酸酯水解的影响。增强树脂 - 牙本质界面的一种策略是将富含氢键的官能团引入牙科粘结树脂中，例如2-脲基-4[1H]-嘧啶酮（UPy）。这些氢键可以连接粘结树脂和含有胶原蛋白及羟基磷灰石的牙本质基质，还能在树脂内部形成非共价交联。在此，我们利用用二醇间隔基修饰的UPy官能化甲基丙烯酰胺，以确保与粘结树脂中常用的其他单体兼容，并促进在树脂 - 牙本质界面以及本体树脂内的氢键形成。合成了三种基于UPy的甲基丙烯酰胺：UPy - OPG400 - MMA、UPy - OPG230 - MMA和UPy - OEG148 - MMA，并将其纳入基于甲基丙烯酸酯的模型粘结配方中。结果表明，UPy - 甲基丙烯酰胺增强了聚合动力学、生物相容性和机械性能。然而，这些改进以及氢键形成的功效取决于二醇间隔基的柔韧性。具体而言，含有UPy - OPG230 - MMA的树脂在水性条件下具有最强健的氢键，使其成为本研究中的最佳选择。微拉伸粘结强度（μTBS）分析和界面表征进一步证实了这一选择，该分析表明，在模型自酸蚀粘结剂中，当50 wt%的甲基丙烯酸2 - 羟乙酯（HEMA）被UPy - OPG230 - MMA取代时，粘结性能有显著提高。总体而言，这项工作提出了一种通过引入增强聚合物网络和树脂 - 牙本质界面的氢键基序来提高牙科粘结剂性能的策略，在临床相关条件下提供了更好的耐久性。意义声明：本研究表明氢键相互作用改善了牙科粘结剂的整体性能。具有2 - 脲基-4[1H]-嘧啶酮（UPy）基团的粘结单体在粘结剂内部以及粘结剂与外部基质（此处为牙本质）之间促进了显著的氢键相互作用。这导致粘结剂的机械完整性得到改善（例如粘结强度和完整性），并影响关键的生物材料性能，如生物相容性。这项工作具有重要意义，因为先前利用UPy功能增强粘结的示范需要与牙科材料原位应用不相容的有机溶剂（如二甲基亚砜）。在这里，我们合成了可与水性溶剂（水、乙醇）混溶且与牙科材料应用中使用的共聚单体兼容的UPy官能化单体。
