A Novel Agent for Oral Surface Conditioning to Control Bacterial Adhesion

 描述(申请人提供)：生物膜是病原体的储存库，几乎在所有表面定居，包括口腔表面；牙菌斑是一种复杂的生物膜。口腔生物膜引起的牙周问题通常是由生物膜形成菌引起的酸化和牙齿脱矿引起的；牙菌斑与牙菌斑有关，如果不加以治疗和控制，可能会导致许多严重的系统性问题。特别是，它们对免疫功能受损的患者造成了严重的健康危害。生物被膜的形成和在表面的定植始于生物被膜细菌的黏附；细菌在载体表面的初始附着对于它们的生存能力、成功的定植和由此产生的感染至关重要。控制牙齿和相关表面菌斑形成的合理方法是定期 用某种能抵抗生物膜形成细菌附着的东西来调节它们。这一阶段的SBIR建议开发一种用于牙齿和相关表面的调理剂，并优化其化学结构，以抑制生物被膜形成细菌的附着。建议将优化后的调理剂用于牙齿清洁配方(例如牙膏、漱口水或清漆)或清洁后冲洗配方。在冲洗过程中(与日常牙齿清洁一样频繁)，该产品将对口腔表面进行表面修饰，以使修改后的牙齿表面和相关表面控制生物膜形成细菌的附着。为了证明在生物材料上抑制细菌黏附作为牙科及相关表面模型的可行性，本研究旨在制备具有不同疏水性/亲水性的调节生物分子，并将其涂覆在牙科相关生物材料模型上，以定量研究涂层表面的细菌黏附和酸化作用，并在连续流培养生物膜模型中生长生物膜，并与相关未涂层对照表面的生物膜进行比较。还建议优化涂层材料的分子结构，以达到最好的抑制细菌黏附、控制乳酸形成和活性的目的。后 完成这项第一阶段研究后，使用本建议中确定的优化生物分子的许多表面调理配方可能会在稍后的第二阶段部分进一步开发。 项目。到目前为止，在宿主中确定感染后，在感染控制方面进行了大量的研究，但结果相当无效，因为几乎所有的疾病溃烂细菌都仍然在生物膜中受到保护，并对治疗剂表现出抗药性。因此，在感染能够站稳脚跟之前，需要对生物膜本身的形成过程进行重大的科学关注。

 DESCRIPTION (provided by applicant): Biofilms are the reservoirs for pathogens and colonize almost all surfaces, including those in the oral cavity; dental plaque is a complex biofilm. Oral biofilms cause periodontal problems commonly induced by acidogenesis and tooth demineralization by biofilm forming bacteria; dental plaque has been associated to and may lead to many serious systemic problems if are it not treated and controlled. In particular, they pose serious health evils to immuno- compromised patients. Biofilm formation and colonization on a surface starts with is the adhesion of biofilm forming bacteria; initial bacterial attachment o the support surface is vital for their viability and successful colonization and the resultant infection. A logical way to control plaque formation on dental and related surfaces is to regularly condition them with something that would resist the attachment of biofilm forming bacteria. This Phase-I SBIR proposes to develop a conditioning agent for dental and related surfaces and the optimization of its chemical structure relative to its ability to inhibit attachment of biofilm foring bacteria. The optimized conditioning agent is proposed to be used in dental cleaning formulations (for example, tooth paste, mouth rinse or varnish) or in a post-cleaning rinse formulation. During the rinses (as frequent as daily dental cleaning), the product will perform surface modification of oral surfaces such that the modified dental and related surfaces would control the attachment of biofilm forming bacteria. To prove the feasibility of inhibition of bacterial adhesion on biomaterials used as the model for dental and related surfaces, it is intended to prepare the proposed conditioning biomolecules with varying degree of hydrophobicity/hydrophilicity and coat them on model dental related biomaterials to quantify the bacterial adherence and acidogenesis on coated surfaces and also to grow biofilm in a continuous flow culture biofilm model and compare to that on the related uncoated control surfaces. It is also proposed to optimize the molecular structure of coating material for the best inhibition of bacterial adherence, control of lactic acid formation and their viability. After the completion of this phase-I study, many surface conditioning formulations using the optimized biomolecules identified in this proposal may be further developed later in the phase-II part of the project. A huge burden of research has been carried out so far on infection control after the infection is established in host, but the results are quite ineffective as almost all disease causig bacteria remain protected in biofilms and show resistance to therapeutic agents. Therefore, a significant scientific attention is needed to control the process of formation of biofilm itself, before the infection could set firm footing.