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-治疗诊断学和特定的挑战主题，13-DE-102：牙科树脂复合材料和龋齿。在美国每年进行的超过100，000万次牙科修复治疗中，大多数涉及树脂粘结复合材料的放置，并且NIH/NIDCR观察到牙医的大部分时间都用于更换这些材料，因此显然需要具有改进的临床性能的材料。复合材料修复剂不仅比牙科汞合金具有美学优势，而且还提供了一种将修复体与牙本质和牙釉质粘合的方法。然而，由于聚合收缩应力从放置时开始挑战该关键界面，并且随着长时间暴露于水性口腔环境，亲水性粘合剂层的公认弱化，目前不能可靠地获得坚固、完整的边缘。这种情况由于向自蚀刻一步粘合剂的转变而加剧，自蚀刻一步粘合剂虽然为从业者提供了更大的便利，但已被证明比两步蚀刻和冲洗粘合剂系统更不可靠。由于需要替换的牙釉质中的高百分比问题与边缘降解、边缘染色和在边缘处形成的继发性龋齿有关，因此似乎非常需要一种显著改进的牙科粘合剂，其可以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该强度和密封能力。最近已经开发了一种高度通用的技术用于制备纳米级（5 - 100 nm）聚合物颗粒，其具有对支化、化学和反应位点布置的控制。这些反应性纳米凝胶可以容易地以高浓度分散在第二单体中，所述第二单体然后渗透并与预聚物添加剂共聚。这种方法提供了聚合收缩和应力的显著降低，以及证明了提高模型牙科粘合剂树脂的强度并在完全水平衡后保持该强度的能力。在牙科粘合剂材料中使用亲水性单体没有合理的替代方案，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，而脱矿牙本质总是保持显著的水分含量。纳米凝胶颗粒可以被设计为适度至极度疏水，同时还提供对基质单体的粘度几乎没有影响的高模量网络结构。纳米凝胶表面，其包括共价连接到基质聚合物的可聚合基团，也可以用亲水性壳改性，该亲水性壳允许对基质单体以及牙本质基底具有很大的亲和力。拟议的项目将验证积极的初步结果，并在两年内，可以预期，这种新技术可以普遍纳入各种传统的牙科粘合剂材料，从而可以提供更强大，更可靠的粘合剂。美国每年有超过1亿例牙科修复，其中大部分是树脂粘合的复合材料，具有良好的初始强度和美观性，但故障/更换率也很高。这些翻修的主要原因是粘合剂完整性恶化，导致细菌泄漏、染色，并可能导致受损牙齿出现新的蛀牙。由于数量非常大，预计粘合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实质性回报。

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.