Tissue-engineered regeneration of the minipig TMJ condyle

项目摘要 大约10 - 25%的人患有颞下颌关节（TMJ）髁突退化。 软骨不会自行愈合，也没有中期干预措施来防止髁突退化， 可能导致危及生命的情况，如气道变化。这项建议旨在改善翻译 组织工程学策略的TMJ髁状突再生走向人类临床使用通过表征 的尤卡坦小型猪下颌髁突，工程新软骨-骨植入物与强大的界面 特性，以及使用新软骨-骨植入物再生TMJ骨软骨缺损的体内研究 髁状突初步的蛋白质组学数据表明，I型和II型胶原蛋白的空间分布可以实现 使用基质辅助激光解吸/电离成像质谱（MALDI-IMS）， 纤维软骨和透明关节软骨。MALDI-IMS将作为一个强大的工具， 尤卡坦小型猪下颌髁突的特征，包括胶原类型的空间分布 I，II，X，and XXVII.这一特征将为组织工程方法提供金标准， 髁状突缺损初步的离体实验表明，在骨软骨上产生骨软骨缺损的可行性很高。 颞下颌关节髁突通过这些新的技术，我将加强TMJ的组织工程方法 髁状突再生在三个特定的目标。在具体目标1中，将使用许多技术，包括MALDI-IMS， 用于表征尤卡坦小型猪的TMJ髁突。这一特征将导致黄金标准 工程组织的价值。在《特定目标2》中，一种新的组织工程技术， 将骨髓间充质干细胞植入脱细胞骨支架中，然后与自组装的新软骨结合， 将被审问。这将导致形成具有坚固界面的新软骨-骨植入物 具有长期体内功效的特性。最后，在特定目标3中，新软骨-骨植入物将用于 大型动物研究，在那里他们将再生尤卡坦小型猪颞下颌关节髁状突的缺陷。成功 这项提案的完成将加强TMJ疾病的组织工程策略的翻译， FDA的临床试验和临床中的人类使用范例。

Project Summary Approximately 10-25% of the population has degeneration of the temporomandibular joint (TMJ) condyle. Cartilage does not heal itself, and there are no mid-stage interventions to prevent condylar degeneration which can lead to life-threatening conditions such as changes to the airway. This proposal aims to improve translation of tissue engineering strategies for TMJ condylar regeneration toward human use in the clinic via characterization of the mandibular condyle of the Yucatan minipig, engineering neocartilage-bone implants with robust interfacial properties, and in vivo studies using neocartilage-bone implants to regenerate osteochondral defects of the TMJ condyle. Preliminary proteomics data show that spatial distributions of collagen types I and II can be achieved using matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS), indicators of fibrocartilage and hyaline articular cartilage, respectively. MALDI-IMS will serve as a powerful tool in a characterization of the Yucatan minipig mandibular condyle, including the spatial distributions of collagen types I, II, X, and XXVII. This characterization will provide gold standards for tissue-engineering approaches to treat condylar defects. Preliminary ex vivo experiments indicate a high feasibility of creating osteochondral defects on the TMJ condyle. Through these novel techniques, I will enhance tissue-engineering approaches for TMJ condyle regeneration in three specific aims. In Specific Aim 1, many techniques, including MALDI-IMS, will be used to characterize the TMJ condyle of the Yucatan minipig. This characterization will result in gold standard values for engineered tissues. In Specific Aim 2, a novel tissue-engineering technique involving seeding of mesenchymal stem cells into decellularized bone scaffolds, then combining with self-assembled neocartilage, will be interrogated. This will result in the formation of neocartilage-bone implants with robust interfacial properties for long term in vivo efficacy. Finally, in Specific Aim 3, neocartilage-bone implants will be used in a large animal study, where they will regenerate defects of the Yucatan minipig TMJ condyle. Successful completion of this proposal will enhance the translation of tissue engineering strategies for TMJ disorders toward the FDA paradigm of clinical trials and human use in the clinic.