DEVELOPMENT OF A WIRELESS BIOSENSOR TO TRACK BONE RESORPTION IN PERIODONTITIS

开发无线生物传感器来追踪牙周炎的骨吸收

• 批准号: 9754630
• 负责人: Shantanu Chakrabartty
• 金额: $ 36.22万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-01 至 2021-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9754630
• 关键词: Affect; Alveolar Bone Loss; Amino Acids; Biological Markers; Biosensor; Bone Density; Bone Matrix; Bone Resorption; C-terminal; Cleaved cell; Clinical; Clinical Markers; Clinical Research; Collagen Type I; Data; Detection; Deterioration; Device or Instrument Development; Devices; Diagnosis; Diagnostic; Diagnostic radiologic examination; Disease; Disease Progression; Drug Delivery Systems; Environment; Europe; FDA approved; Feedback; Future; Gingival Crevicular Fluid; Goals; Grant; Human; Implant; Inflammatory; Intervention; Investigation; Japan; Label; Link; Liquid substance; Matrix Metalloproteinases; Measurement; Measures; Mechanics; Metabolic Bone Diseases; Methods; Mission; Monitor; National Institute of Dental and Craniofacial Research; Onset of illness; Oral; Osteoclasts; Osteoporosis; Outcome; Patients; Peptides; Periodontal Diseases; Periodontitis; Preclinical Testing; Prevention strategy; Quality of life; Rattus; Resolution; Safety; Saliva; Serum; Severities; Severity of illness; Structure of gingival sulcus; System; Technology; Telemetry; Testing; Therapeutic Intervention; Time; Tooth Loss; Tooth structure; Treatment Efficacy; Ultrasonics; United States; Wireless Technology; Work; alveolar bone; base; biomaterial compatibility; bone; bone loss; bone mass; bone turnover; cathepsin K; clinical biomarkers; collagenase; crosslink; design; disease diagnosis; glutamyl-lysyl-alanyl-histidyl-aspartyl-glycyl-glycyl-arginine; high risk; high risk population; improved; in vivo; indexing; multidisciplinary; periodontopathogen; public health relevance; pyridinoline; sensor; skeletal; treatment response

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.

项目总结/摘要 牙周病是一种多因素的炎症性疾病，在美国影响超过6400万人。 导致牙槽骨吸收，临床附着丧失，最终导致牙齿脱落。电流 检测方法依赖于囊袋深度的机械评估和骨的射线照相检测 恶化当注意到这种疾病时，要完全扭转病情已经太晚了。我们将 开发一种无线生物传感器，以量化两种公认的骨吸收生物标志物，ICTP和β-CTx， 在龈沟液中可检测到，并与牙周病的严重程度，发病和 分辨率这两种生物标志物都是I型胶原蛋白的稳定裂解产物，I型胶原蛋白是最丰富的有机 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系统将改善高危患者牙周病的临床检测， 减少当前牙龈沟液分析固有的变异性和延长的分析时间 方法，其中没有一种是FDA批准用于临床的。为了完成这项工作，我们将采取三项具体措施， 目标。首先，我们将在压电传感器上合成肽特异性生物识别层， 使用中孔壳保护其免受体内环境的影响。其次，我们将优化标签方法- 基于超声波供电、询问的生物标志物浓度的自由、体内、无线测量 和遥测技术。第三，除了设备开发，我们还将生成和编译安全和 用于支持临床可行性试验的试验用器械豁免（IDE）申请的有效性数据。 完成后，我们建议将我们的生物传感器用作预防策略，以准确识别 牙周病高危患者在骨受损之前加速骨骼退化 质量或密度，从而促进及时干预和成功治疗。除了追踪疾病 在高危人群中发病，需要准确的、基于生物传感器的纵向监测， 牙周骨丢失的进展与阻止，从而确定治疗干预的功效。的 这项资助的工作与NIDCR的使命一致，即监测牙周炎的动态变化。 疾病，包括区分进展与停滞状态以及对治疗的反应。