Improved Resin Bonded Dental Restoratives Based on Nanogel-modified Adhesives

描述(由申请人提供)：本申请涉及广泛的挑战领域(13)智能生物材料-Theranostics和具体的挑战主题13-DE-102：牙科树脂复合材料和龋齿。在美国每年进行的10多亿次牙科修复治疗中，大部分涉及树脂粘结复合材料的植入，而且NIH/NIDCR观察到，牙医大部分时间都花在更换这些修复体上，因此显然需要具有更好临床性能的材料。与牙科汞合金相比，复合修复剂不仅具有美学优势，而且提供了一种将修复体粘结到牙本质和牙釉质上的方法。然而，由于聚合收缩应力从放置时就挑战了这一关键界面，以及众所周知的亲水性粘结层随着长时间暴露在含水口腔环境中而变弱，目前无法可靠地获得坚固、完整的边际。这种情况因转向自酸蚀一步粘合剂而加剧，这种粘合剂虽然为从业人员提供了更大的便利，但已被证明比两步酸蚀和漂洗粘合剂系统更不可靠。由于需要更换的修复体中有很大比例的问题与边缘退化、边缘染色和边缘形成的继发性龋齿有关，因此似乎非常需要一种大幅改进的牙科粘结剂，能够提供显著更大的初始强度，最重要的是，在口腔环境中长期保持这种强度和封闭能力。最近发展了一种高度通用的技术来制备纳米级(5-100 nm)聚合物粒子，并控制支化、化学和反应位置。这些反应性纳米凝胶可以很容易地在高浓度的二次单体中分散，然后渗透到预聚体添加剂中并与其共聚。这种方法大大减少了聚合收缩和应力，并证明了有能力提高模型牙科粘接树脂的强度，然后在完全水平衡后保持该强度。在牙科粘接材料中使用亲水性单体没有合理的替代方法，因为这些树脂必须能够很好地渗透到牙本质小管和脱矿牙本质中，而脱矿牙本质始终保持着显著的水分含量。纳米凝胶颗粒可以设计成具有中等到极强的疏水性，同时还提供了对基质单体粘度影响很小的高模数网络结构。纳米凝胶表面包括共价附着到基质聚合物上的可聚合基团，也可以用亲水性外壳进行修饰，该外壳允许对基质单体以及牙本质基质有很大的亲和力。拟议的项目将验证积极的初步结果，预计在两年内，这项新技术可以普遍应用到各种传统牙科粘结材料中，从而可以获得更坚固、更可靠的粘结修复体。美国每年有超过1亿个牙科修复体，其中大部分是树脂粘结复合材料，具有良好的初始强度和美观性，但也有很高的失败率/替换率。进行这些修改的一个主要原因是粘结剂完整性的恶化，这会导致细菌泄漏、染色，并可能在受损的牙齿中开始新的腐烂。由于数量非常多，预计粘接强度和长期可靠性的显著改善将在更少的患者就诊和昂贵的更换程序以及改善整体口腔健康方面产生可观的回报。

DESCRIPTION (provided by applicant): This application addresses the broad Challenge Area (13) Smart Biomaterials - Theranostics and the specific Challenge Topic, 13-DE-102: Dental Resin Composites and Caries. With a majority of the more than 100,000 million dental restorative treatments performed in the US each year involving the placement of resin-bonded composite materials, and the observation from NIH/NIDCR that a large portion of a dentist's time is consumed with replacing these restorations, there is a clear need for materials with improved clinical performance. Composite restoratives not only hold an esthetic advantage over dental amalgams, but they offer a means to adhesively bond the restoration to dentin and enamel. However, due to polymerization shrinkage stresses that challenge this critical interface from the time of placement and a well-recognized weakening of the hydrophilic adhesive layer with prolonged exposure to the aqueous oral environment, a strong, intact margin can not currently be reliably obtained. This situation is being exacerbated by the shift towards self-etching one-step adhesives which while providing greater convenience to the practitioner, have proven to be even less reliable than the two-step etch and rinse adhesive systems. Since a high percentage of the problems in restorations requiring replacement are linked to marginal degradation, marginal staining and secondary caries formed at the margins, this appears to be great need for a substantially improved dental adhesive that can offer significantly greater initial strength and most importantly, the retention of that strength and sealing ability long term in the oral environment. A highly versatile technique has been developed recently for preparing nano- scale (5 - 100 nm) polymeric particles with control over branching, chemistry and reactive site placement. These reactive nanogels can be dispersed readily in high concentration in secondary monomers which then infiltrate and copolymerize with the prepolymer additives. This approach has provided dramatic reductions in polymerization shrinkage and stress, as well as a demonstrated ability to improve the strength of a model dental adhesive resin and then maintain that strength after complete water equilibration. There is no reasonable alternative to the use of hydrophilic monomers in dental adhesive materials since these resins must be able to penetrate well into the dentinal tubules and demineralized dentin which always retains significant moisture content. The nanogel particles can be designed to be moderately to extremely hydrophobic while also providing a high modulus network structure that has little effect on viscosity of the matrix monomer. The nanogel surface, which includes polymerizable groups to covalently attach to the matrix polymer, can also be modified with a hydrophilic shell that allows great affinity for the matrix monomer as well as the dentin substrate. The proposed project would validate the positive preliminary results and within two years, it can be expected that this new technology could be generically incorporated in to a wide variety of traditional dental adhesive materials with the result that stronger, more reliable bonded restorations could be available. There are over 100 million dental restorations placed in the US each year and most of these are resin-bonded composite materials which have good initial strength and esthetics but also a high failure/replacement rate. A primary reason for these revisions is the deterioration of the adhesive integrity which allows bacterial leakage, staining, and potentially the onset of new decay in the compromised tooth. Because of the very large numbers, the predicted significant improvements in adhesive strength and long-term reliability will generate a substantial return in fewer patient visits and expensive replacement procedures as well as improved overall oral health.