TMJ Disc Regeneration

项目摘要/摘要 颞下颌关节紊乱病(TMJ)是第二常见的肌肉骨骼疾病 疾病，导致疼痛和残疾，每年给美国经济造成40亿美元的损失。TMD代表着一个 TMJ椎间盘状况的谱系，从小(局灶性)、部分厚度(椎间盘变薄)病变开始， 最终长成大的、全厚度(穿孔)缺陷。这次竞争性更新的总体目标是 是通过使用无支架组织来治疗跨越TMJ椎间盘缺损症的TMJ病变- 工程学。建立在成功修复局灶性视盘变薄缺陷的基础上， 我们将扩大可以通过组织工程化TMJ椎间盘植入物解决的临床适应症。在 在父母的资助下，我们设计并植入了具有42%天然椎间盘特性的TMJ特异性仿生组织 在小型猪中形成直径3 mm的视盘变薄缺陷。与空白对照相比，使用 无支架种植体修复TMJ局灶性视盘变薄的缺陷：1)导致4.4倍的完全缺陷 闭合和2)形成3.4倍更坚硬的修复组织。未治疗组的骨关节炎评分是对照组的3.0倍 种植体治疗组。对于这次竞争性更新，使用微型猪，适应症将扩大1) 从盘变薄到穿孔缺陷；2)从局灶性缺陷到大缺陷，最后达到3) 修复大的穿孔缺陷。拟议的研究包括三个目标，每个目标都包含一个体外 阶段以设计适合于目标适应症的组织，随后使用 猪模。目标1的目标是治愈病灶(直径3毫米)。TMJ盘穿孔缺陷使用组织- 经过改造的TMJ植入物具有更好的功能。目标2的目标是治愈大直径(6 mm直径)。光盘- 高传代组织工程大片种植体减薄猪模型的实验研究 肋软骨细胞。从这些目标发展而来的技术诀窍将被转化为目标3，以实现大型组织工程， 用于治疗大型穿孔缺陷的坚固的植入物。估计有900万名患者患有 在TMJ盘穿孔和更多有盘变薄缺陷的情况下，成功完成了建议的 这项工作将进一步翻译组织工程疗法，以解决一个重要的医学问题，即 目前还没有令人满意的长期解决方案。

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.