TMJ Disc Regeneration

描述（由申请人提供）： 该应用程序的长期目标是使用综合组织重建方法成功解决颞下颌关节（TMJ）椎间盘的再生问题。有一个明确的需要再生颞下颌关节盘，以减轻需要椎间盘切除术，在严重的情况下，椎间盘移位。70%的颞下颌关节紊乱病患者患有椎间盘移位，这可能导致椎间盘退变和/或穿孔，并可表现为颌部咔嗒声、锁定和剧烈疼痛。我们的研究的主要假设是，我们可以再生的TMJ光盘结构相比，通过使用肽修饰的，生物可降解的支架与生长因子，细胞和机械刺激的适当组合，增强扩散的天然光盘。为了验证这一假设，我们提出了以下具体目标：1）在组织水平上表征TMJ盘，2）在细胞水平上描述TMJ盘，3）体外工程化TMJ盘。这项全面的研究将为未来的体内研究奠定基础，以取代受损的颞下颌关节盘植入失败。此外，由于颞下颌关节盘是一个知之甚少的组织，共同提出的研究将提供广泛和详细的知识的结构功能特性的正常颞下颌关节盘。这一重要信息将允许定义设计和确认标准，以设计椎间盘结构。为了在组织水平上表征关节盘，将检查原生猪TMJ关节盘以确定超微结构、拉伸和压缩下的生物力学特性以及生化含量和组织。为了在细胞水平上描述椎间盘，将阐明细胞拓扑结构，将鉴定亚群，并将在二维聚（丙二醇单油酸酯-共-乙二醇）-GRGD表面上培养细胞，其中将在存在不同生长因子的情况下测量增殖和生物合成。一旦天然椎间盘被表征，将使用结合在天然椎间盘形状的支架内的最佳生长因子，使用旋转生物反应器、间歇静水压力和直接压缩/拉伸的组合来创建工程化椎间盘。在不同的时间点，将工程化构建体的性质与确定的天然椎间盘性质进行比较。拟议的研究代表了一种新的方法来再生颞下颌关节盘，因为我们打算首先进行必要的表征研究，然后使用细胞接种的支架，生物活性因子，机械信号和增强的扩散，以促进椎间盘再生。

DESCRIPTION (provided by applicant): The application's long-term objective is to use a comprehensive tissue reconstruction approach to successfully address regeneration of the temporomandibular joint (TMJ) disc. There is a clear need to regenerate the TMJ disc to alleviate the need for discectomy in severe cases of disc displacement. Seventy percent of patients with temporomandibular disorders suffer from disc displacement, which can result in disc degeneration and/or perforation and can be manifested in jaw clicking, locking and severe pain. The chief hypothesis of our study is that we can regenerate a TMJ disc construct comparable to the native disc by the use of a peptide-modified, biodegradable scaffold with the appropriate combination of growth factors, cells and mechanical stimuli with enhanced diffusion. To test this hypothesis, we propose the following specific aims: 1) To characterize the TMJ disc at the tissue level, 2) to describe the TMJ disc at the cellular level and 3) to engineer the TMJ disc in vitro. This comprehensive study will lay the groundwork for future in vivo studies to replace damaged TMJ discs where implants have failed. Furthermore, since the TMJ disc is a poorly understood tissue, collectively the proposed studies will provide broad and detailed knowledge of structure-function properties of the normal TMJ disc. This vital information will allow the definition of design and validation criteria to engineer disc constructs. To characterize the disc at the tissue level, native porcine TMJ discs will be examined to determine ultrastructure, biomechanical properties under tension and compression, and biochemical content and organization. To describe the disc at the cellular level, cellular topography will be elucidated, subpopulations will be identified, and cells will be cultured on two dimensional poly(propylene fumarate-co-ethylene glycol)-GRGD surfaces where proliferation and biosynthesis will be measured with varied growth factors present. Once the native disc is characterized, an engineered disc will be created using the optimal growth factors incorporated within the scaffold in the shape of a native disc, using a combination of a rotating bioreactor, intermittent hydrostatic pressure and direct compression/tension. At various time points, properties of the engineered constructs will be compared to the determined native disc properties. The proposed research represents a novel approach to regenerate the TMJ disc in that we intend to first perform the necessary characterization studies and then use cell-seeded scaffolds, bioactive factors, mechanical signals and enhanced diffusion to facilitate disc regeneration.