Cartilage Shaping for Biological Resurfacing/Replacement of the TMJ

描述（由申请人提供）：颞下颌关节疾病（TMJD），包括骨关节炎和内部紊乱，在成年人中发病率很高，经常引起疼痛和颌骨功能受限。下颌髁突关节软骨的严重退化可发生在TMJD的晚期病例，可能需要通过髁突切除术进行手术切除。自体、同种异体和同种异体移植重建下颌髁已被尝试过，但这些植入材料通常伴有并发症，包括供体部位发病率、疾病传播风险和免疫原性反应。软骨和骨的组织工程可以通过生产具有适当生物和力学性能的移植物来解决治疗颞下颌关节痛的重要和未满足的临床需求。一种基于组织工程的TMJD治疗方法可能是通过创建形状合适的软骨移植物，该移植物可以单独用于髁突表面或与骨基质结合以重建整个髁突。将软骨组织塑造成解剖形式的能力可能是这种治疗方法的一种使能技术。因此，本项目的长期目标是为创建轮廓关节软骨移植物建立科学原理和工程方法，以有效地进行TMJD的手术治疗。最近的研究表明，通过机械刺激，特别是弯曲变形，可以在体外诱导未成熟关节软骨外植体的形状变化。我们的总体假设是，关节软骨的形状可塑性可能受到蛋白聚糖（PG）和胶原蛋白（COL）重塑（通过BAPN或p- d -木糖苷）失衡的差异调节，并可能有利于创造人类下颌髁突软骨大小和形状的移植物。为了验证这个假设，我们有两个目的。目的1：确定体外生长有利于PG或COL重塑（分别通过BAPN或p - d -木糖苷）是否会改变未成熟和成熟关节软骨的形状可塑性。目的2：通过关节软骨外植体的机械整形，确定能否产生与人下颌髁突软骨大小和形状相同的软骨移植物。这项跨学科研究的成功结果将是确定有利于形成解剖形状的软骨组织的培养条件和技术。总的来说，这些发现对于使用再生医学治疗颞下颌关节和关节紊乱具有广泛的临床意义。

DESCRIPTION (provided by applicant): Temporomandibular joint disorders (TMJD), including osteoarthritis and internal derangement, have a high prevalence in the adult population and often cause pain and limited jaw function. Severe deterioration of the articular cartilage of the mandibular condyle can occur in advanced cases of TMJD and may necessitate surgical removal via condylectomy. Reconstruction of the mandibular condyle has been attempted using autogenous, allogeneic, and alloplastic grafts, but these implant materials are often associated with complications including donor site morbidity, risk of disease transmission, and immunogenic reaction. Tissue engineering of cartilage and bone may address the significant and unmet clinical need for treating TMJD through the ability to produce grafts with appropriate biological and mechanical properties. One approach to a tissue engineering based treatment for TMJD might be through the creation of an appropriately shaped chondral graft which could be used alone to resurface the condyle or integrated to an osseous substrate to reconstruct the entire condyle. The ability to shape cartilaginous tissues into anatomical forms could be an enabling technology to this treatment approach. Thus, the long-term goal of this project is to establish scientific principles and engineering methods for the creation of contoured articular cartilage grafts for the effective surgical treatment of TMJD. Recent studies have shown that shape changes can be induced in immature articular cartilage explants in vitro through the use of mechanical stimuli, particularly bending deformations. Our overall hypothesis is that the shape plasticity of articular cartilage may be differentially modulated by imbalances in proteoglycan (PG) and collagen (COL) remodeling (via BAPN or p-D-xyloside) and may be used advantageously to create grafts of the size and shape of human mandibular condyle cartilage. To test this hypothesis, we have two aims. Aim 1: Determine whether in vitro growth which favors PG or COL remodeling (via BAPN or P-D-xyloside, respectively) alters the shape plasticity of immature and mature articular cartilage. Aim 2: Determine whether chondral grafts of the size and shape of human mandibular condyle cartilage can be produced through the mechanical reshaping of articular cartilage explants. The successful outcome of this interdisciplinary study will be the identification of culture conditions and techniques which are conducive to the formation of anatomically shaped chondral tissues. These findings will have broad clinical implications for the use of regenerative medicine in the treatment of disorders of the TMJ and articulating joints, in general.