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

描述（由申请人提供）：目前治疗牙根发育不完全和根管系统坏死的儿童恒牙的方法充满困难。不仅根管系统通常难以完全消毒，而且薄的牙本质壁增加了随后的牙根断裂的风险，这通常需要拔牙。虽然这可能发生在所有儿童（例如，创伤），来自卫生保健不平等家庭的儿童由于龋齿的患病率较高而面临特别的风险。目前治疗这些病例的标准方法是根尖诱导成形术（在根尖形成/诱导钙化屏障），这会导致牙齿严重弱化，长期预后不良。最近报道的再生手术是一种合理的治疗替代方案。它涉及根管系统的化学消毒，然后诱发出血进入根管系统，形成血凝块并立即进行冠状密封。这种新方法建立在组织工程的概念基础上，利用了丰富的间充质干细胞供应，可能包括邻近未完全发育牙齿的开放顶点的根尖乳头（SCAP）干细胞群。该R34资助申请的目的是计划和开发后续的U 01临床试验方案申请，该方案将测试中心假设，即与标准治疗（MTA根尖诱导成形术）相比，涉及使用三联抗生素糊剂和诱发根管系统出血的再生临床方案将产生显著更大的牙本质壁厚度的持续发展。这将是一项前瞻性、III期、随机、多中心（3个研究中心：UTHSCSA、UCSF、UCSF）对照临床试验。在目前的R34计划期内，我们将实现以下目标：具体目标1：制定一份全面的临床试验方案，其中包括指定的招募策略和相关文件，如程序手册、IRB方案、知情同意书、临床研究者手册、培训手册和拟议预算（用于U 01申请）。具体目标2：培训和校准研究团队，使方案程序和数据收集标准化。具体目标3：开发数据管理所需的工具和协议，以及适当和有效的研究安全和操作监督。 公共卫生相关性：该项目与公共卫生有关，因为来自卫生保健不平等家庭的儿童往往有更大的风险因龋齿或其他因素而失去恒牙。通过研究一种新的基于生物学的方法来治疗感染并使牙齿继续发育，该项目直接解决了与公共卫生高度相关的关键问题。

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.