ECM MEDIATED DENTAL PULP TISSUE REGENERATION

描述(申请人提供)：美国和世界上每年都有数以百万计的成年人和儿童患有与龋齿及其治疗相关的问题。目前的临床实践不足以使丢失的牙髓组织再生。国家牙科和颅面研究所(NIDCR)是国家卫生研究所(NIH)的一部分，它将大量资源投入到针对这些组织再生的研究上。根据NIDCR的使命和重点，该项目专注于开发一种用于再生完整和功能牙髓组织的仿生支架。具体地说，我们打算将牙髓细胞的细胞外基质(ECM)整合到3D支架中，在小型猪牙髓切除模型中驱动体内体细胞干细胞的分化。这项研究包括两个特定的目标，目的是在一个大型动物临床前模型中再生牙髓，并了解再生的分子机制和独特的多功能蛋白在这一过程中的参与。在体内实验中，我们计划将ECM支架与目前的临床标准进行比较，以分析它们是否能够更好地发挥作用，并证明它们在初步的体外和体内实验中所显示的潜力是合理的。这一项目的结果有可能用患者特有的再生疗法取代目前的根管治疗。含有ECM的支架可以批量生产，它们的使用将使牙髓组织工程应用中不再需要生长因子输送系统。此外，这项研究还将为一个全新的系统奠定平台，以分析多功能蛋白在干细胞分化和组织再生中的细胞外作用。

DESCRIPTION (provided by applicant): Every year millions of adults and children in the United States and in the world suffer from caries and its treatment related problems. Current clinical practices are not adequate to enable regeneration of the lost dental pulp tissue. The National Institute of Dental and Craniofacial Research (NIDCR), a part of the National Institute of Health (NIH) has devoted much of its resources towards research that targets regeneration of these tissues. In accordance with the mission and the focus of the NIDCR, this project focuses on the development of a biomimetic scaffold for regeneration of complete and functional dental pulp tissue. Specifically, we intend to use the extracellular matrix (ECM) of pulp cells incorporated into 3D scaffolds to drive the differentiation of somatic stem cells in vivo in a mini pig pulpectomy model. This study consists of two specific aims directed at regeneration of dental pulp in a large animal pre-clinical model and understanding the molecular mechanism of regeneration and the involvement of unique multifunctional proteins in this process. In the in vivo experiments, we plan to compare the ECM scaffolds side by side with the current clinical standards to analyze if they are able to perform better and justify the potential that they have shown in our preliminary in vitro and in vivo experiments. Results from this project have the potential to replace current root canal therapy with patient- specific regenerative therapy. The ECM incorporated scaffolds can be mass-produced and their use will remove the need growth factor delivery systems from dental pulp tissue engineering applications. Additionally, the study will also lay the platform for a totally new system to analyze extracellular roles of multifunctionl proteins in stem cell differentiation and tissue regeneration.