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.

项目摘要 大约10%-25%的人患有颞下颌关节(TMJ)髁状突退行性变。 软骨不会自行愈合，也没有中期干预措施来防止髁状突退变 可能导致危及生命的情况，如呼吸道改变。这项建议旨在提高翻译水平。 TMJ组织工程技术在临床上的临床应用 尤卡坦小型猪下颌骨髁突的研究--界面坚固的工程化新型骨种植 新骨移植修复TMJ骨软骨缺损的特性和体内研究 髁状突。初步的蛋白质组学数据显示，可以实现I型和II型胶原的空间分布 使用基质辅助激光解吸/电离成像质谱仪(MALDI-IMS)，指示剂 纤维软骨和透明关节软骨。MALDI-IMS将作为一种强大的工具 尤卡坦小型猪下颌骨髁状突的特征，包括胶原类型的空间分布 I、II、X和XXVII。这一特征将为组织工程学治疗提供黄金标准 髁状突缺陷症。初步的体外实验表明，在体内制造骨软骨缺陷的可能性很高。 TMJ髁状突。通过这些新技术，我将增强TMJ的组织工程学方法 在三个特定的目标下进行髁突再生。在具体目标1中，包括MALDI-IMS在内的许多技术将是 用来描述尤卡坦小型猪的TMJ关节。这一特征将导致金本位制。 工程组织的价值。在特定目标2中，一种新的组织工程技术涉及种植 将间充质干细胞制成脱细胞骨支架，然后与自组装的新骨结合， 将被审问。这将导致新的人工骨种植体的形成，具有坚固的界面 具有长期的体内药效。最后，在具体目标3中，新人工骨植入物将用于 大型动物研究，在那里他们将再生尤卡坦小型猪TMJ关节突的缺陷。成功 这项提议的完成将加强TMJ障碍的组织工程策略的翻译，以 FDA的临床试验范例和临床中的人类使用。