NIDCR Dentist Scientist K99:Improve TMJ Fibrocartilage Regeneration Strategies

描述（由申请人提供）：颞下颌关节（TMJ）髁突由纤维软骨组织组成，目前研究尚不充分。创伤或TMJ纤维软骨慢性变性的患者严重虚弱。目前，还没有有效的治疗方法来再生永久性损伤或退化的纤维软骨组织，这主要是由于我们严重缺乏TMJ纤维软骨生物学知识。很少有研究明确阐明和定义TMJ纤维软骨细胞成分或评估TMJ的再生特性。我们的初步数据表明，第一次，在颞下颌关节髁突假定的干/祖细胞的存在。为了测试推定的TMJ干/祖细胞再生的应用，我们建立了体内手术TMJ髁突置换模型。因此，我们的长期目标是1）分离和全面表征推定的TMJ干/祖细胞; 2）确定表征的TMJ干/祖细胞在生物材料支架中的再生潜力。我们的总体假设是TMJ含有干/祖细胞，可以利用生物材料支架进行TMJ再生。我们的目标是再生颞下颌关节纤维软骨，逐渐接近天然组织在多个，反复在体内实验中，在骨骼成熟的动物模型。总的来说，这些研究预计不仅可以提高我们对纤维软骨生物学和再生的理解，而且还可能有助于纤维软骨损伤和疾病的新型再生疗法的发展。

DESCRIPTION (provided by applicant): 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.