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

基本信息

批准号：
9980197
负责人：
Shantanu Chakrabartty
金额：
$ 36.22万
依托单位：
WASHINGTON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-08-01 至 2022-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9980197
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

项目摘要

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.

项目概要/摘要牙周病是一种多因素炎症性疾病，影响美国超过 6400 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。检测方法依赖于袋深度的机械评估和骨的放射线检测当病情恶化时，我们要完全扭转病情就已经太晚了。开发一种无线生物传感器来量化两种成熟的骨吸收生物标志物 ICTP 和 β-CTx，可以在龈沟液中检测到，并且与牙周病的严重程度、发作和发生相关两种生物标志物都是 I 型胶原蛋白（最丰富的有机胶原蛋白）的稳定裂解产物。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，同时减少当前龈沟液分析固有的变异性并延长分析时间方法，但这些方法均未获得 FDA 批准用于临床。为了完成这项工作，我们将追求三种特定的方法。首先，我们将在压电传感器上合成肽特异性生物识别层。使用介孔壳保护其免受体内环境影响其次，我们将优化标记方法。基于超声波供电、询问的生物标志物浓度的免费体内无线测量第三，除了设备开发之外，我们还将生成和编译安全性和安全性。研究性器械豁免 (IDE) 申请的功效数据，以支持临床可行性测试。完成后，我们建议将我们的生物传感器用作预防策略，以准确识别在骨质受损之前，牙周病高危患者的骨骼会加速恶化质量或密度，从而除了跟踪疾病之外还促进及时干预和成功治疗。在高危人群中发病，需要基于生物传感器的准确、纵向监测来确定与阻止牙周骨进展损失的比较，从而确定治疗干预的效果。这笔赠款的工作符合 NIDCR 监测牙周动态的既定使命疾病，包括区分进行性停滞状态和对治疗的反应。