Biocatalytic Nanocomposites to Prevent Formation of Dental Plaque

描述（由申请人提供）：我们建议开发高活性和稳定的防污和自清洁涂层，以抵抗细菌生物膜的形成，并提供抵抗口腔细菌定植的第一道防线。通过利用酶-纳米材料-聚合物复合结构，我们将生成针对生物膜形成途径中多个步骤的多功能涂层。这些涂层将降解吸附的蛋白质，这些蛋白质形成“调节膜”，介导细菌附着，将是杀微生物的（直接对细菌有效），也将降解构成生物膜的基质的主要成分多糖。这些涂层在很长一段时间内是稳定的，不需要再生，并且在机械上是坚固的。本研究的前提是，这种活性和稳定的含酶涂层将提供一种生物相容性、高选择性和有效的治疗方法，以对抗导致牙齿疾病的机制，特别是牙齿和口腔种植体上牙菌斑的形成。我们的初步工作已经证明我们有能力产生完全抑制蛋白质吸附的自清洁复合材料。此外，我们已经证明，纳米尺度的载体显著提高了吸附酶的稳定性，从而使复合膜具有更高的活性和长期稳定性。

DESCRIPTION (provided by applicant): We propose to develop highly active and stable antifouling and self-cleaning coatings that resist bacterial biofilm formation and provide a first line of defense against oral bacterial colonization. By taking advantage of enzyme-nanomaterial-polymer composite architectures, we will generate multifunctional coatings that target multiple steps in the pathway to biofilm formation. These coatings will degrade adsorbed proteins that form a "conditioning film" mediating bacterial attachment, will be microbicidal (directly active against bacteria), and will also degrade polysaccharides that are major components of the matrix comprising a biofilm. These coatings will be stable for long periods without need for regeneration, and will be mechanically robust. The premise of this study is that such active and stable enzyme-containing coatings will provide a biocompatible, highly selective, and potent therapy against the mechanisms that lead to dental disease, particularly the formation of dental plaque on teeth and oral implants. Our preliminary work has already demonstrated our ability to generate self-cleaning composites that completely inhibit protein adsorption. Furthermore, we have shown that supports having nanoscale dimensions dramatically enhance the stability of adsorbed enzymes, leading to composite films with greater activity and long-term stability. The specific goals of this work are: 1. To elucidate the mechanism of enzyme activation and stabilization on nanoscale materials, such as singlewalled carbon nanotubes, carbon buckyball aggregates, and metallic nanoparticles. This information is critical to design optimal enzyme-nanomaterial-polymeric composites with antifouling and self-cleaning properties. 2. To incorporate selected enzymes identified in Aim 1 into optimal enzyme-nanomaterial-polymer composites and demonstrate the antifouling and self-cleaning capacity of these surfaces under conditions, in vitro, that mimic long-term oral use. These studies will be the foundation for the design and implementation of antifouling and self-cleaning enzyme-nanomaterial-polymeric composite coatings and films for long-term use in the mouth. The results generated during this R21 grant will form the basis for a more comprehensive R01 submission and ultimate collaboration with a clinical partner.