NIDCR Dentist Scientist K99:Improve TMJ Fibrocartilage Regeneration Strategies

项目摘要 颞下颌关节(TMJ)髁状突由纤维软骨组织组成，实质上是 未得到充分研究。TMJ纤维软骨损伤或慢性退变的患者严重 虚弱的。目前，还没有有效的治疗方法来再生永久性的损伤或退化。 纤维软骨组织，很大程度上是由于我们严重缺乏对TMJ纤维软骨生物学的了解。很少有研究 曾专门阐明和定义TMJ纤维软骨细胞成分或评估再生 TMJ的属性。我们的初步数据第一次证明了推定的 TMJ内的干/祖细胞。测试可能的TMJ干/祖细胞在治疗中的应用 在此基础上，建立了TMJ体内置换手术模型。因此，我们的长期- 学期目标是1)分离和全面鉴定可能的TMJ干/祖细胞；2)确定 具有特征性的TMJ干/祖细胞在生物材料支架中的再生潜力。我们的整体 假设TMJ含有干细胞/祖细胞，可用于TMJ的生物材料支架 再生。我们的目标是再生TMJ纤维软骨，使其逐渐接近于 在骨骼成熟的动物模型中进行多次重复的活体实验。总的来说，这些研究是 期望不仅能增进我们对纤维软骨生物学和再生的了解，而且还可以 有助于开发治疗纤维软骨损伤和疾病的新的再生疗法。

Project Summary The temporomandibular joint (TMJ) condyle consists of fibrocartilage tissue and is substantially understudied. Patients with either trauma or chronic degeneration of TMJ fibrocartilage are severely debilitated. Currently, there are no effective treatments that regenerate permanently damaged or degenerated fibrocartilage tissue, largely due to our severe lack of knowledge in TMJ fibrocartilage biology. Few studies have specifically elucidated and defined TMJ fibrocartilage cellular constituents or assessed the regenerative properties of the TMJ. Our preliminary data demonstrate, for the first time, the presence of putative stem/progenitor cells in the TMJ condyle. To test the application of putative TMJ stem/progenitor cells for regeneration, we have established a surgical TMJ condyle replacement model in vivo. Accordingly, our long- term goals are1) to isolate and comprehensively characterize putative TMJ stem/progenitor cells; 2) determine the regenerative potential of characterized TMJ stem/progenitor cells in biomaterial scaffolds. Our overall hypothesis is the TMJ harbors stem/progenitor cells that can be harnessed in biomaterial scaffolds for TMJ regeneration. Our goal is to regenerate TMJ fibrocartilage that gradually approximates the native tissue in multiple, reiterative in vivo experiments in skeletally mature animal models. Overall, these studies are anticipated to not only to enhance our understanding of fibrocartilage biology and regeneration, but may also contribute to the development of novel regenerative therapies for fibrocartilage injuries and diseases.