Tissue-engineered regeneration of the minipig TMJ condyle

小型猪颞下颌关节髁的组织工程再生

• 批准号: 10679842
• 负责人: Benjamin Bielajew
• 金额: $ 6.99万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-11 至 2026-04-10
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10679842
• 关键词: Adult; Affect; Age; American; Animal Model; Animals; Arthralgia; Benchmarking; Biochemical; Biochemistry; Biological Assay; Biomechanics; Biomimetics; Bone Morphogenetic Proteins; Cartilage; Cartilage Matrix; Clinic; Clinical; Clinical Trials; Collagen Type I; Collagen Type II; Collagen Type X; Data; Defect; Degenerative polyarthritis; Engineering; Faculty; Failure; Fibrocartilages; Financial Support; Funding; Glycerophosphates; Goals; Gold; Histologic; Histology; Human; Hyaline Cartilage; Immunohistochemistry; Implant; Intervention; Life; Liquid substance; Mandibular Condyle; Maps; Mechanics; Mentors; Mesenchymal Stem Cells; Methodology; Methods; Miniature Swine; Modeling; Morphology; Natural regeneration; Operative Surgical Procedures; Patients; Phase; Population; Positioning Attribute; Postdoctoral Fellow; Process; Property; Proteomics; Reporting; Research; Safety; Spatial Distribution; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Structure of articular disc of temporomandibular joint; Techniques; Temporomandibular Joint; Temporomandibular Joint Disorders; Tensile Strength; Time; Tissue Engineering; Tissues; Training; Translations; Triiodothyronine; Universities; analog; articular cartilage; bone; bone marrow mesenchymal stem cell; bone scaffold; calcification; cartilage implant; cartilage regeneration; condylar cartilage; design; experimental study; improved; in vivo; in vivo Model; interfacial; mass spectrometric imaging; mechanical properties; mechanical stimulus; novel; osteochondral tissue; pre-clinical; prevent; self assembly; success; tissue regeneration; tool

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.

项目概要 大约 10-25% 的人口患有颞下颌关节 (TMJ) 髁突退变。 软骨不会自行愈合，并且没有中期干预措施来预防髁突变性 可能导致危及生命的情况，例如气道变化。该提案旨在改进翻译 通过表征研究用于临床人类使用的 TMJ 髁突再生的组织工程策略 尤卡坦小型猪的下颌髁突，工程新软骨骨植入物具有坚固的界面 特性，以及使用新软骨骨植入物再生颞下颌关节骨软骨缺陷的体内研究 髁。初步蛋白质组学数据表明可以实现 I 型和 II 型胶原蛋白的空间分布 使用基质辅助激光解吸/电离成像质谱 (MALDI-IMS)，指标 分别为纤维软骨和透明关节软骨。 MALDI-IMS 将作为一个强大的工具 尤卡坦半岛小型猪下颌骨髁的表征，包括胶原蛋白类型的空间分布 I、II、X 和 XXVII。这一表征将为组织工程方法治疗提供黄金标准 髁突缺陷。初步的离体实验表明在其上制造骨软骨缺陷具有很高的可行性 颞下颌关节髁。通过这些新技术，我将增强颞下颌关节的组织工程方法 髁突再生有三个具体目标。在具体目标 1 中，包括 MALDI-IMS 在内的许多技术将被 用于表征尤卡坦小型猪的颞下颌关节髁。这种特征将产生黄金标准 工程组织的值。在具体目标 2 中，一种新颖的组织工程技术涉及播种 将间充质干细胞转化为脱细胞骨支架，然后与自组装的新软骨结合， 将会被审问。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，在具体目标 3 中，新软骨骨植入物将用于 大型动物研究，他们将再生尤卡坦半岛小型猪颞下颌关节髁的缺陷。成功的 该提案的完成将促进颞下颌关节紊乱的组织工程策略的转化 FDA 临床试验和临床人体使用范例。