Multilayer Scaffold for Condyle Surface Regeneration

项目摘要 最严重的颞下颌关节疾病包括下颌骨髁突变性。可惜没有 存在再生选择，并且当前的治疗不能恢复全部功能。关节的组织 髁突是一种纤维软骨，由纤维、软骨和骨之间的复杂界面组成 正常功能所必需的组织，在严重的TMJ疾病中丢失。本研究的目的 目的：用胶原纤维修复成年山羊下颌骨髁状突纤维软骨-骨界面， 全面的组织工程方法。我假设多层支架将允许位点特异性 下颌骨髁突软骨的纤维-软骨-骨再生， 海绵支架和未处理的对照缺陷。首先，我将研究多层支架设计的特性 在体外。我将表征TGFβs从支架的渗透性和释放。第二，我将研究 髁突上发现的三种细胞亚群的再生潜力。第三，我会把支架植入 山羊下颌骨髁状突缺损，并评估其功能再生的潜力。这项建议 强调PI将在整个培训期间做出的贡献， 主要专注于完成支架的制作和表征，以及研究 TMJ细胞亚群在体外的再生潜力和我们的双层支架在体内的再生潜力。 成功完成这项建议是关键的一步，提供再生疗法，以治疗颞下颌关节 下颌骨软骨退变和其他部位成功骨软骨组织再生的基础。

PROJECT SUMMARY The most severe cases of TMJ disorders consist of mandibular condyle degeneration. Unfortunately, no regenerative options exist, and current treatments do not restore full function. The articulating tissue of the condyle is a fibrocartilage that consists of an intricate interface between fibrous, cartilaginous, and boney tissue that is essential for normal function and that is lost in severe TMJ disorders. The objective of this study is to regenerate fibrocartilage-bone interface of the mandibular condyle in skeletally mature goats using a comprehensive tissue engineering approach. I hypothesize that a multilayer scaffold will allow for site-specific fibrous-cartilage-bone regeneration of the mandibular condyle cartilage when compared to a homogenous sponge scaffold and untreated control defects. First, I will study the properties of a multilayer scaffold design in-vitro. I will characterize the permeability and release of TGFβs from the scaffold. Second, I will study the regeneration potential of three cell subpopulations found on the condyle. Third, I will implant our scaffold in mandibular condyle defects of goats and assess their potential for functional regeneration. This proposal highlights the contributions that the PI will make throughout the duration of the training, which will primarily focus on the completion of scaffold fabrication and characterization, as well as the study of the regenerative potential of TMJ cells subpopulations in vitro and of our bilayer scaffold in vivo. Successful completion of this proposal is the critical step to providing a regenerative therapy to treat TMJ mandibular cartilage degeneration and a basis for successful osteochondral tissue regeneration in other sites.