Characterization of Pulp Inflammation: an Observational Study Using Biological Samples Collected During Routine Dental Care
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 1,200
- 主要终点
- Gene expression levels in inflamed dental pulp tissues
研究概览
简要总结
Background: Vital pulp therapy (VPT) is a cornerstone of minimally invasive dentistry and aims to preserve pulp vitality whenever clinically feasible. Teeth with vital pulp show better long-term survival than endodontically treated teeth. However, the success of VPT procedures-such as indirect or direct pulp capping, partial pulpotomy, and full pulpotomy-critically depends on an accurate assessment of the extent and severity of pulpal inflammation. Current diagnostic classifications are mainly based on patient-reported symptoms and sensibility tests, which do not reliably reflect the underlying inflammatory status of the pulp tissue. This diagnostic uncertainty contributes to inappropriate treatment selection, early therapeutic failures, and wide variability in clinical practice.
Rationale: Pulpal inflammation is a dynamic and spatially heterogeneous biological process that progresses from localized to diffuse tissue involvement. Clinical studies have demonstrated discrepancies between clinical diagnosis and the actual histological and molecular status of the pulp. A new diagnostic classification (Endolight) has been proposed to better guide VPT indications by distinguishing different stages of pulpal inflammation, but it has not yet been validated against in situ biological analyses of human pulp tissue. Moreover, the identification of molecular and protein biomarkers associated with inflammatory severity could support the development of more accurate diagnostic and prognostic tools for endodontic decision-making.
Objectives: The primary objective of this study is to characterize the immune and inflammatory response of human dental pulp at the tissue, transcriptomic, and proteomic levels using biological samples obtained during routine dental care. Secondary objectives are to assess the concordance between clinical diagnostic categories-particularly those of the Endolight classification-and pulpal inflammatory profiles, and to explore associations between inflammatory profiles and patient-related or tooth-related factors.
Methods: This is a prospective, monocentric observational study conducted at the Department of Dental Medicine of Pitié-Salpêtrière Hospital. Pulp tissue samples and whole pulp-containing teeth are collected as operative waste during routine endodontic treatments or tooth extractions. Samples are pseudonymized and processed according to the planned analyses. Transcriptomic profiling is performed using RNA sequencing, with validation by RT-qPCR, in situ hybridization and RNAscope. Protein expression and activity are assessed using proteomic approaches, ELISA assays, and immunohistochemical or immunofluorescence analyses. Clinical, demographic, and dental data are collected from medical records using a secured electronic case report form.
Outcomes: Primary outcomes include the identification and characterization of inflammatory gene and protein expression profiles in human dental pulp. Secondary outcomes include the concordance between clinical diagnoses and biological inflammatory profiles, as well as the identification of molecular biomarkers potentially relevant for guiding VPT indications.
Expected impact: By improving the biological characterization of pulpal inflammation and its relationship with clinical diagnosis, this study aims to support more precise, biology-driven decision-making in vital pulp therapy and the management of endodontic emergencies.
详细描述
Vital pulp therapy (VPT) is a key component of minimally invasive dentistry and aims to preserve pulp vitality whenever clinically feasible. Teeth with vital pulp have been shown to exhibit better long-term survival than endodontically treated teeth. Consequently, VPT procedures-including indirect pulp capping, direct pulp capping, partial pulpotomy, and full pulpotomy-should be preferred over root canal treatment when the biological status of the pulp allows it.
The success of VPT relies on two essential factors: the use of bioactive materials capable of promoting pulpal healing, and an accurate assessment of the severity and extent of pulpal inflammation. However, complications related to inappropriate case selection remain frequent and often occur within the first year following treatment. These failures are largely attributed to the difficulty of precisely evaluating the inflammatory status of the pulp, highlighting a major unmet need in endodontic diagnosis, particularly in the context of emergency care.
Pulpal inflammation is a defense response of the dental pulp to external aggression such as carious lesions, fractures, periodontal disease, or restorative procedures. This biological process is dynamic, progressive, and spatially heterogeneous. Inflammation initially develops locally in the pulp tissue adjacent to the injury and may subsequently extend to involve the entire coronal pulp and, in more advanced stages, the radicular pulp. When inflammation remains confined to the coronal pulp, removal of the inflamed tissue through partial or total pulpotomy followed by the application of a bioactive material may be sufficient to achieve healing and long-term success.
At the clinical level, however, the assessment of pulpal inflammation remains challenging. The most widely used diagnostic classification of pulpal diseases is mainly based on patient-reported pain characteristics and responses to thermal sensibility tests. This classification distinguishes healthy pulp, reversible pulpitis, irreversible pulpitis (acute or chronic), and pulp necrosis. Intraoperative criteria, such as the evaluation of bleeding and hemostasis, are sometimes used to estimate pulpal status, but these criteria remain subjective and poorly standardized.
Several studies have demonstrated discrepancies between clinical diagnosis and the actual histological condition of the pulp tissue. Moreover, the current diagnostic framework does not allow a clear correspondence between clinical diagnosis and the indication for specific VPT procedures. While four VPT techniques are available, only three inflammatory diagnostic categories are recognized, which contributes to uncertainty in therapeutic decision-making and significant variability in clinical practice.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •- Adult patients (≥18 years old) whose pulp tissue must be removed during routine dental care, either through endodontic treatment or tooth extraction for orthodontic, surgical, prosthetic, or periodontal reasons.
- •Patients who have been informed about the study and have not expressed opposition to participation
排除标准
- •- Patients who have taken anti-inflammatory medication within 12 hours prior to the dental procedure.
- •Patients under legal protection measures (e.g., guardianship or curatorship).
结局指标
主要结局
Gene expression levels in inflamed dental pulp tissues
时间窗: At the time of pulp tissue collection (baseline)
Quantitative assessment of gene expression levels using RNA sequencing (normalized expression counts), comparing different clinical diagnosis of pulpitis (according to Endolight classification).
次要结局
- Relative gene expression validation by RT-qPCR profile(At the time of pulp tissue collection (baseline))
- Protein concentration levels in inflamed dental pulp tissues(At the time of pulp tissue collection (baseline))
- Protein abundance profiles by mass spectrometry(Assessment of protein abundance and degradation patterns using mass spectrometry-based proteomics (relative intensity or spectral counts).)
- Cytokines expression in pulp tissues(At the time of pulp tissue collection (baseline))
- Association between molecular markers and clinical parameters(At the time of pulp tissue collection (baseline))
- Spatial gene expression by RNAscope in inflamed pulp tissues(At the time of pulp tissue collection (baseline))