DEVELOPMENT OF A WIRELESS BIOSENSOR TO TRACK BONE RESORPTION IN PERIODONTITIS

项目摘要/摘要 牙周病是一种多因素的炎症性疾病，影响着美国超过300万人 导致牙槽骨吸收、临床附着丧失，并最终导致牙齿脱落的状态。当前 检测方法依赖于口袋深度的机械评估和骨骼的射线检测 恶化。当这种疾病被发现时，已经太晚了，无法完全扭转这种情况。我们会 开发一种无线生物传感器来量化两个公认的骨吸收生物标志物，ICTP和β-CTX， 可在牙龈沟液中检测到，并与牙周病的严重程度、发病和 决议。这两种生物标志物都是I型胶原的稳定裂解产物，I型胶原是最丰富的有机物质 骨基质的组成部分。我们的中心假设是实施基于生物传感器的监测 ICTP和β-CTX系统将改进高危患者牙周病的临床检测，同时 减少分析的可变性和延长分析时间，这是目前的牙龈沟液分析所固有的 方法，没有一种是FDA批准用于临床的。为了完成这项工作，我们将进行三项具体的工作 目标。首先，我们将在压电式传感器上合成多肽特异性生物识别层，这是 使用介孔壳保护其不受体内环境的影响。二是优化标注方式-- 基于超声波供电、询问的免费、活体、无线生物标记物浓度测量 在老鼠身上进行遥测。第三，除了设备开发，我们还将生成和编译安全和 研究设备豁免(IDE)应用的疗效数据，以支持临床可行性测试。 完成后，我们建议使用我们的生物传感器作为预防策略，以准确识别 在骨骼受损之前，牙周病高危患者的骨骼加速退化 质量或密度，从而促进及时干预和成功治疗。除了跟踪疾病之外 在高危人群中发病，需要基于生物传感器的准确、纵向监测来建立 牙周骨丢失的进展与停止，因此决定了治疗干预的效果。这个 这项赠款的工作与NIDCR规定的监测牙周动态的使命是一致的 疾病，包括区分进展状态和停滞状态以及对治疗的反应。

Project Summary/Abstract Periodontal disease is a multifactorial inflammatory condition affecting over 64 million people in the United States that leads to alveolar bone resorption, clinical attachment loss, and, eventually, tooth loss. Current detection methods rely on mechanical assessment of pocket depth and radiographic detection of bone deterioration. By the time the disease is noted, it is already too late to fully reverse the condition. We will develop a wireless biosensor to quantify two well-established biomarkers of bone resorption, ICTP and β-CTx, that are detectable in the gingival crevicular fluid and correlate with periodontal disease severity, onset and resolution. Both biomarkers are stable cleavage products of type I collagen – the most abundant organic component of the bone matrix. Our central hypothesis is that implementation of a biosensor-based monitoring system for ICTP and β-CTx will improve clinical detection of periodontal disease in high-risk patients while reducing the variability and extended time to analysis inherent to current gingival crevicular fluid analysis methods, none of which are FDA-approved for clinical use. To complete this work we will pursue three specific aims. First, we will synthesize a peptide-specific bio-recognition layer on a piezoelectric sensor that is protected from the in vivo environment using a mesoporous shell. Second, we will optimize methods for label- free, in vivo, wireless measurement of biomarker concentration based on ultrasonic powering, interrogation and telemetry in rats. Third, in addition to device development, we will generate and compile safety and efficacy data for an investigational device exemption (IDE) application to support clinical feasibility testing. When complete, we propose that our biosensor be used as a preventive strategy to accurately identify accelerated skeletal deterioration in patients at high-risk for periodontal disease, prior to a compromise in bone mass or density, thus promoting timely intervention and successful therapy. In addition to tracking disease onset in high-risk populations, accurate, longitudinal biosensor-based monitoring is needed to establish progression vs arrest of periodontal bone loss and thus determine the efficacy of therapeutic interventions. The work in this grant is consistent with the stated mission of the NIDCR to monitor the dynamics of periodontal disease, including differentiating between progressive versus arrested states and responses to treatment.