Project Title

POC Biosensor for Periodontitis

Principal Investigator/Project Director

Toshihisa Kawai

Colleges / Centers

College of Dental Medicine

Funder

U.S. DHHS NIH - National Institute of Dental and Craniofacial Research

Start Date

6-2-2020

Abstract

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 earlyresponse 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.

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