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，基本上未被充分研究。患者无论是外伤或慢性退行性颞下颌关节纤维软骨严重衰弱。目前，由于我们对TMJ纤维软骨生物学知识的严重缺乏，尚无有效的治疗方法来再生永久性损伤或变性的纤维软骨组织。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。我们的初步数据首次证明，在TMJ髁中存在假定的干细胞/祖细胞。为了测试推测的TMJ干细胞/祖细胞在再生中的应用，我们在体内建立了TMJ髁移位手术模型。因此，我们的长期目标是1)分离和全面表征假定的TMJ干细胞/祖细胞；2)确定表征的TMJ干细胞/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含有干细胞/祖细胞，这些细胞可以用于TMJ再生的生物材料支架。我们的目标是在骨骼成熟的动物模型中，通过多次反复的体内实验，再生逐渐接近天然组织的TMJ纤维软骨。总的来说，这些研究不仅可以增强我们对纤维软骨生物学和再生的理解，而且还可以促进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. PUBLIC HEALTH RELEVANCE: There are no clinical therapies to regenerate diseased or damaged temporomandibular joint (TMJ) fibrocartilage. The long-term goals of our proposal are to characterize putative TMJ stem/progenitor cells and to determine their potential to regenerate TMJ fibrocartilage using 3D biomaterial scaffolds. We propose to develop tissue-engineering strategies for biological TMJ condyle substitutes and anticipate these studies to be critical for the development of regenerative treatments for patients suffering from TMJ disease or injury.