ECM MEDIATED DENTAL PULP TISSUE REGENERATION

描述（由申请人提供）：每年在美国和世界上有数百万的成人和儿童患有龋齿及其治疗相关问题。目前的临床实践不足以使失去的牙髓组织再生。作为美国国立卫生研究院（NIH）的一部分，美国国立牙科和颅面研究所（NIDCR）已经将其大量资源投入到针对这些组织再生的研究中。根据NIDCR的使命和重点，本项目侧重于开发一种用于完整和功能性牙髓组织再生的仿生支架。具体来说，我们打算在一个小型的猪髓切除术模型中使用髓细胞的细胞外基质（ECM）结合到3D支架中来驱动体内体细胞干细胞的分化。本研究包括两个特定的目标，即在大型动物临床前模型中进行牙髓再生，以及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对比，以分析它们是否能够表现得更好，并证明它们在我们初步的体外和体内实验中显示出的潜力。这个项目的结果有可能用患者特异性再生疗法取代目前的根管治疗。结合ECM的支架可以批量生产，它们的使用将消除牙髓组织工程应用中对生长因子输送系统的需求。此外，该研究还将为建立一个全新的系统来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奠定基础。

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.