TMJ Disc Regeneration

项目总结/摘要 颞下颌关节（TMJ）疾病（TMD）是第二常见的肌肉骨骼疾病， 这种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代表了 颞下颌关节盘状况的频谱，开始于小（局灶性），部分厚度（椎间盘变薄）病变， 最终生长成大的全厚度（穿孔）缺陷。此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颞下颌关节病变， 工程.在成功治愈局灶性椎间盘变薄缺陷的基础上，在父母补助金中证明， 我们将扩大组织工程颞下颌关节盘植入物的临床适应症。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为3 mm的椎间盘变薄缺陷。与空白对照相比， 无支架植入物通过1）诱导4.4倍以上的完全缺损来愈合TMJ局灶性椎间盘变薄缺损 闭合和2）形成3.4倍更硬的修复组织。未治疗组的骨关节炎评分为3.0倍 植入物治疗组。对于本次竞争性更新，使用小型猪，适应症将扩大1） 从盘变薄到穿孔缺陷，2）从局部缺陷到大缺陷，最终达到3） 大穿孔缺损的愈合。拟议的研究包括三个目标，每个目标包含一个体外 阶段，以工程组织适合的目标的适应症，其次是一个大型动物研究，使用 猪模型目标1的目标是治愈病灶（直径3 mm）颞下颌关节盘的穿孔缺陷， 改良功能的颞下颌关节植入物。目标2的目标是愈合大（直径6 mm）表示“圆盘”之义 通过组织工程化大植入物形成的猪模型中的薄化缺陷， 肋软骨细胞从这些目标中开发的技术将转化为目标3，以进行大型组织工程， 用于治疗大穿孔缺损的坚固植入物。估计有900万患者 穿孔的颞下颌关节盘和更多的光盘变薄的缺陷，成功完成了建议 这项工作将进一步转化组织工程疗法，以解决一个重要的医学问题， 目前还没有令人满意的长期解决办法。

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.