TMJ Disc Regeneration

颞下颌关节盘再生

• 批准号: 10238212
• 负责人: Kyriacos A Athanasiou
• 金额: $ 6.5万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-12-01 至 2022-01-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10238212
• 关键词: Address; Affect; Animals; Area; Autopsy; Biochemical; Biological Assay; Biomechanics; Biomimetics; Blood; Caliber; Cells; Clinical; Clinical Research; Defect; Degenerative polyarthritis; Elements; Engineering; Environment; Epidemiology; Exhibits; Foundations; General Population; Goals; Histology; Immune; Immunology; Implant; In Situ; In Vitro; Knowledge; Left; Lesion; Liquid substance; Mechanics; Medical; Methods; Miniature Swine; Modeling; Morbidity - disease rate; Musculoskeletal; Operative Surgical Procedures; Pain; Patients; Perforation; Phase; Phenotype; Property; Regimen; Safety; Secure; Solid; Stimulus; Structure of articular disc of temporomandibular joint; Symptoms; Techniques; Temporomandibular Joint; Temporomandibular Joint Disorders; Testing; Thick; Thinness; Time; Tissue Donors; Tissue Engineering; Tissues; Translating; Translations; Validation; Work; base; cost; disability; disc regeneration; efficacy evaluation; efficacy testing; fluid flow; healing; improved; improved functioning; indexing; joint destruction; novel; parent grant; porcine model; prevent; public health relevance; scaffold; success; tissue repair

Project Summary / Abstract Temporomandibular joint (TMJ) disorders (TMD) represent the second most common musculoskeletal condition, resulting in pain and disability, costing the US economy $4 billion per year. TMD represent a spectrum of TMJ disc conditions, beginning with small (focal), partial-thickness (disc-thinning) lesions that eventually grow into large, full-thickness (perforation) defects. The overall objective of this competitive renewal is to treat TMJ lesions that span the spectrum of TMJ disc defect conditions via the use of scaffold-free tissue- engineering. Building on the successful healing of focal disc-thinning defects, demonstrated in the parent grant, we will expand the clinical indications that can be addressed by tissue-engineered TMJ disc implants. In the parent grant, we engineered and implanted TMJ-specific biomimetic tissues with 42% of native disc properties into disc-thinning defects 3mm in diameter in the minipig. Compared to empty controls, treatment with the scaffold-free implants healed TMJ focal disc-thinning defects by 1) inducing 4.4-times more complete defect closure and 2) forming 3.4-fold stiffer repair tissue. The osteoarthritis score of the untreated group was 3.0-fold of the implant-treated group. For this competitive renewal, using the minipig, indications will be broadened 1) from disc-thinning to perforation defects and 2) from focal defects to large defects, to culminate in 3) the healing of large perforation defects. The proposed study comprises three aims, each containing an in vitro phase to engineer tissues appropriate for the aim's indication, followed by a large animal study using the porcine model. The goal of Aim 1 is to heal focal (3mm dia.) perforation defects of the TMJ disc using tissue- engineered TMJ implants with improved functionality. The objective of Aim 2 is to heal large (6mm dia.) disc- thinning defects in the porcine model by tissue-engineering large implants formed with highly passaged costochondral cells. Knowhow developed from these aims will be translated to Aim 3 to tissue-engineer large, robust implants for the treatment of large perforation defects. With an estimated 9 million patients having perforations in the TMJ disc and many more with disc-thinning defects, successful completion of the proposed work will further the translation of tissue-engineering therapies for an important medical problem that is currently without satisfactory long-term solutions.

项目摘要 /摘要 颞下颌关节（TMJ）疾病（TMD）代表第二常见的肌肉骨骼 病情，导致疼痛和残疾，每年造成40亿美元的经济。 TMD代表 TMJ光盘条件的光谱从小（焦点），部分厚度（椎间盘稀释）病变开始 最终成长为大的全厚度（穿孔）缺陷。这种竞争更新的总体目标 是通过使用无脚手架的组织来处理跨越TMJ椎间盘缺陷条件频谱的TMJ病变 工程。基于父母赠款中证明 我们将扩大组织工程TMJ椎间盘植入物可以解决的临床指示。在 父母赠款，我们设计和植入了TMJ特异性仿生组织，具有42％的本机盘特性 在粉饰上呈斑点缺陷，直径为3mm。与空对照相比 无脚手架的植入物治愈了TMJ焦点椎间盘损伤的缺陷1）诱导4.4次更完整的缺陷 闭合和2）形成3.4倍更硬的修复组织。未处理组的骨关节炎评分为3.0倍 植入物处理的组。对于这种竞争性更新，使用Minipig，指示将扩大1） 从椎间盘稀释到穿孔缺陷，以及2）从局灶性缺陷到大缺陷，再到3） 大型穿孔缺陷的愈合。拟议的研究包括三个目标，每个目标都包含体外 阶段与适合AIM指示的组织组织，然后是一项大型动物研究 猪模型。 AIM 1的目的是使用组织治愈TMJ光盘的局灶性（3mm）穿孔缺陷。 具有改进功能的工程TMJ植入物。 AIM 2的目的是治愈大（6mm直径）。 通过高度传递形成的组织工程大型植入物在猪模型中的稀疏缺陷 cos骨细胞。从这些目标中发展的知识将被转化为AIM 3到大型组织工程师， 鲁棒植物用于治疗大型穿孔缺陷。估计有900万患者 TMJ光盘中的穿孔以及其他椎间盘损伤缺陷，成功完成建议的缺陷 工作将进一步翻译组织工程疗法，以解决重要的医学问题 目前没有令人满意的长期解决方案。