POC Biosensor for Periodontitis

用于牙周炎的 POC 生物传感器

• 批准号: 10177999
• 负责人: TOSHIHISA KAWAI
• 金额: $ 19.97万
• 依托单位: NOVA SOUTHEASTERN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-06-02 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10177999
• 关键词: ADORA2A gene; Adenosine; Affect; Anti-Inflammatory Agents; Aspartate Transaminase; BMP2 gene; Binding; Biological; Biological Markers; Biosensor; CD100 antigen; Calculi; Caring; Cells; Clinical; Collection; Consumption; Detection; Development; Devices; Diagnosis; Disease; Elderly; Endothelial Cells; Enzyme-Linked Immunosorbent Assay; Enzymes; Evaluation; Future; Gingiva; Gingival Indexes; Gingivitis; Health; Hemorrhage; Immune; Inflammation; Inflammation Mediators; Inflammatory; Inflammatory Response; Interleukin-1 beta; Lab-On-A-Chips; Lesion; Ligation; Liquid substance; MMP8 gene; Measurement; Measures; Mental Retardation; Monitor; Oral cavity; Osteogenesis; Outcome; P2X-receptor; Paper; Pathogenicity; Patients; Periodontal Pocket; Periodontitis; Periodontium; Plant Roots; Population; Prediction of Response to Therapy; Predictive Value; Procedures; Production; Prognosis; Regenerative response; Regulatory T-Lymphocyte; Reporting; Risk Factors; Role; Sampling; Series; Severities; Site; Standardization; Study Subject; Sum; TNF gene; Temporomandibular Joint; Testing; Time; Tissues; Tooth structure; aged; base; biomarker panel; bone; cell injury; cohort; collagenase; cytokine; extracellular; healing; neutrophil; next generation; novel; novel strategies; operation; osteogenic; periapical; receptor; recruit; regenerative; response; tissue regeneration; tool; tooth crowding; treatment response

For nearly a century, practitioners have typically relied on periodontal probing to diagnose periodontitis. Based on a strong positive correlation between pocket depth and severity of periodontitis, the primary purpose of periodontal probing is to measure pocket depths around a tooth in order to establish the state of health of the periodontium. However, periodontal probing is a time-consuming chairside procedure and has little predictive value in determining current disease activity, prognosis of future progression, or healing in response to treatment, essentially because scant quantitative biological information gained from measuring pocket depth. In this study, we will use “lab-on-a-chip” device, SMARTChip® Biosensor, to measure extracellular ATP (eATP) and extracellular Adenosine (eADO) in GCF. More specifically, GCF collected from patients using a paper point will be diluted into PBS and immediately applied to SMARTChip at chairside. Unlike other subjective POC devices, enzyme-based amperometric SMARTChip® can quantify eATP and eADO in GCF. Recent studies have demonstrated that eATP released from damaged cells or activated neutrophils is causal for inflammatory responses by binding with a series of purinergic P2X and P2Y receptors. This eATP induces proinflammatory factors, such as TNF-α and IL-1β, from innate immune cells, suggesting that eATP is an early- response inflammatory mediator. Meanwhile, ectonucleotidases, CD39 and CD73, produced by Treg and Breg cells, as well as endothelial cells convert ATP to anti-inflammatory eADO. We have learned that eADO, by ligation with its specific ADO receptor, suppresses inflammation by down-modulating TNF-α and IL-1β expressions, and promotes the production of BMP2. These lines of evidence suggest that eATP is associated with inflammation, but that eADO may function as an anti-inflammatory and pro-osteogenesis factor in periodontitis. Our hypothesis holds that SMARTChip® measurements of eATP/eADO in GCF will serve to determine inflammatory status in periodontitis lesion and act as a predictor of bone regenerative responses. In order to test this hypothesis we will validate POC SMARTChip® measurements of eATP and eADO in GCF for the diagnosis periodontitis and prediction of treatment-related bone regenerative activities. Three cohorts will be recruited for this study; A) control healthy subjects, B) gingivitis patients and C) periodontitis patients. Conventional periodontal measurements (pocket depth, clinical attachment loss, bleeding on probing and gingival index) and standardized periapical radiograph will be performed. Then, GCF will be collected by a PerioPaper (GCF Collection Strip) at the deepest periodontal pocket or gingival crevice from each quadrant, and the concentrations of eATP and eADO will be monitored at chairside using a SMARTChip®. A panel of biomarkers will be monitored in GCF using Luminex® Multiplex which will be compared to eATP/eADO for correlation with the clinical measurements of pocket depth and clinical attachment loss as well as treatment- related bone regenerative activities in the study subjects.

在近一个世纪以来，从业者通常依靠牙周探测来诊断牙周炎。基于 在口袋深度和牙周炎严重程度之间存在很强的正相关性，主要目的是 牙周探测是为了确定牙齿周围的口袋深度，以建立 牙周。但是，牙周探测是一项耗时的椅子旁程序，几乎没有预测性 在确定当前疾病活动，未来进展的进展或响应治疗后的愈合方面的价值， 本质上是因为从测量口袋深度中获得的定量生物学信息很少。在这项研究中， 我们将使用“实验室芯片”设备Smartchip®生物传感器来测量细胞外ATP（EATP）和 GCF中的细胞外腺苷（EADO）。更具体地说，使用纸点从患者那里收集的GCF将 将其稀释到PBS中，并立即应用于SmartChip。与其他主观POC设备不同， 基于酶的AmperometricSmartChip®可以在GCF中量化EATP和EADO。 最近的研究表明，来自受损细胞或激活的中性粒细胞释放的EATP是因果 通过与一系列嘌呤能P2X和P2Y受体结合来进行炎症反应。这种吃的影响 来自先天免疫细胞的促炎因子，例如TNF-α和IL-1β，表明EATP是早期的 反应炎症介质。同时，由Treg和Breg生产的Ectonucleotidass，CD39和CD73 细胞以及内皮细胞将ATP转换为抗炎EADO。我们已经了解到Eado， 通过其特定的ADO受体结扎，通过下调TNF-α和IL-1β抑制注射 表达并促进BMP2的产生。这些证据表明eatp是相关的 随着炎症，这种EADO可能在 牙周炎。我们的假设认为，GCF中的SmartChip®eatp/EADO的测量将用于 确定牙周炎病变的炎症状态，并充当骨再生反应的预测指标。在 为了检验该假设 诊断牙周炎和治疗相关骨再生活性的预测。三个队列将是 为这项研究招募； a）控制健康受试者，b）牙龈炎患者和c）牙周炎患者。 常规的牙周测量（口袋深度，临床附着损失，探测和 将执行牙龈指数）和标准化的根尖X射线照片。然后，GCF将通过 最深的牙周口袋或每个象限的牙龈缝隙处的佩里皮纸（GCF收集条）， EATP和EADO的浓度将使用SmartChip®在椅子侧进行监控。一个面板 将使用Luminex®多路复用在GCF中监视生物标志物 与口袋深度和临床附着损失的临床测量以及治疗的相关性 研究对象中相关的骨再生活性。