REGENERATION OF PULP-DENTIN DEVELOPMENT IN IMMATURE PERMANENT TEETH WITH NECROSIS

坏死的未成熟恒牙牙髓牙本质发育的再生

基本信息

批准号：
7876114
负责人：
Kenneth M Hargreaves
金额：
$ 24.69万
依托单位：
UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-07-06 至 2012-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7876114
关键词：
Address Antibiotics Apical Applications Grants Blood Clot Blood coagulation Budgets Calcified Chemicals Child Clinical Clinical Investigator Clinical Protocols Clinical Trials Clinical trial protocol document Consent Forms Controlled Clinical Trials Data Data Collection Dental Pulp Dental Pulp Necrosis Dental caries Dentin Development Diagnosis Disinfection Family Fracture Grant Healthcare Hemorrhage Infection Left Manuals Mesenchymal Stem Cells Methods Minerals National Institute of Dental and Craniofacial Research Natural regeneration Necrosis Outcome Measure Pamphlets Paste substance Phase Plant Roots Prevalence Procedures Protocols documentation Public Health Pulp Canals Randomized Reporting Research Research Ethics Committees Research Personnel Risk Safety Site Specific qualifier value Standardization System Testing Thick Tissue Engineering Tooth Extraction Tooth structure Training Trauma alternative treatment base data management novel strategies outcome forecast permanent tooth prospective public health relevance regenerative seal standard care stem cell population tongue papilla tool

项目摘要

DESCRIPTION (provided by applicant): The current method for treating a child's permanent tooth with an incompletely developed root and a necrotic root canal system is fraught with difficulty. Not only is the root canal system often difficult to fully disinfect, but the thin dentinal walls increase the risk of a subsequent root fracture, which often necessitates extraction of the tooth. Although this may occur in all children (eg., trauma), children from families with health care disparities are at particular risk due to a greater prevalence of caries. The current standard method of treating these cases is apexification (formation/induction of a calcified barrier across the root apex), which leaves a greatly weakened tooth with a poor long term prognosis. A recently reported regenerative procedure is a plausible treatment alternative. It involves the chemical disinfection of the root canal system followed by evoked bleeding into the root canal system, formation of a blood clot and immediate coronal seal. Built upon the concepts of tissue engineering, this new approach takes advantage of a rich supply of mesenchymal stem cells, possibly including the population of stem cells of the apical papilla (SCAP) that is adjacent to the open apex of the incompletely developed tooth. The objective of this R34 grant application is to plan and develop a subsequent U01 clinical trial protocol application that will test the central hypothesis that a regenerative clinical protocol, that involves the use of a triple antibiotic paste and evoked bleeding into the root canal system, will produce significantly greater continued development of dentinal wall thickness as compared to standard treatment (MTA apexification). This will be a prospective, Phase III, randomized, multi-center (3 sites: UTHSCSA, UCSF, UNC) controlled clinical trial. In the present R34 planning period, we will accomplish the following aims: Specific Aim 1: Develop a comprehensive clinical trial protocol that includes specified recruitment strategies and associated documents such as a Manual of Procedures, IRB protocol, consent form, clinical investigator's brochure, training manual, and proposed budget (for the U01 application). Specific Aim 2: Train and calibrate the research team for standardization of protocol procedures and data collection. Specific Aim 3: Develop tools and protocols required for data management, and appropriate and effective safety and operational oversight of the research. PUBLIC HEALTH RELEVANCE: This project is relevant to public health since children from families with health care disparities often have a greater risk of losing their permanent teeth due to caries or other factors. By studying a new and biologically-based method for treating infection and allowing the tooth to continue its development, this project directly addresses a key issue of high relevance to public health.

描述（由申请人提供）：当前的方法是用根部不完整的根源和坏死根管系统处理的永久性牙齿，这充满了困难。根管系统不仅通常难以完全消毒，而且薄牙本质壁会增加随后的根部断裂的风险，这通常需要提取牙齿。尽管这可能发生在所有儿童（例如创伤）中，但由于龋齿的患病率更高，患有医疗保健差异的家庭的儿童尤其面临着特别的风险。治疗这些病例的当前标准方法是顶端化（跨根尖的钙化屏障的形成/诱导），这留下了大大削弱的牙齿，长期预后较差。最近报道的再生程序是一种合理的治疗方法。它涉及根管系统的化学消毒，然后引起诱发到根管系统，形成血块和立即冠状密封。基于组织工程的概念，这种新方法利用了丰富的间充质干细胞的优势，可能包括与不完全发育不完全发育的牙齿开放的顶点相邻的顶端乳头干细胞（SCAP）的人群。该R34赠款应用的目的是计划和开发随后的U01临床试验协议应用，该规程将检验以下中心假设，即涉及使用三重抗生素糊的再生临床方案，并唤起将其渗入根管系统，将产生与标准治疗相比的牙龈壁厚厚度的更大的持续发展（MMTA EPA相比）。这将是一项前瞻性，第三阶段，随机，多中心（3个地点：UTHSCSA，UCSF，UNC）对照临床试验。在当前的R34计划期内，我们将完成以下目的：具体目标1：制定全面的临床试验方案，其中包括指定的招聘策略和相关文件，例如程序手册，IRB协议，同意形式，临床研究人员的手册，培训手册，培训手册和建议的预算（U01应用程序）。特定目标2：训练和校准研究团队，以进行协议程序和数据收集的标准化。特定目的3：开发数据管理所需的工具和协议，以及对研究的适当有效的安全和操作监督。公共卫生相关性：该项目与公共卫生有关，因为来自卫生保健差异家庭的儿童通常会因龋齿或其他因素而丧失其恒牙的风险更大。通过研究一种基于生物学的新方法来治疗感染并允许牙齿继续开发，该项目直接解决了与公共卫生高度相关的关键问题。