Tissue Engineered Tendon Complex for Rotator Cuff Repair and Regeneration

项目摘要/摘要 肩袖撕裂是常见的、致残的，也是代价高昂的肌肉骨骼损伤。外科修复是一种常见的 治疗后，20%至90%的患者会出现复发的泪水，尤其是那些裂口很大或很大的患者。 生物材料强化的肩袖修复，包括机械强化以增加修复 强度和生物愈合加速组织再生，可减少术后并发症。 然而，目前用于增强的移植物材料远远不能令人满意。组织工程学提供 然而，产生功能性组织替代的潜力，设计了一种合适的支架，可以 具有固有的肌腱力学性能，并为细胞种植、生长和 分化，尤其是肌腱末端的再生，已经被证明是具有挑战性的。在此应用程序中，我们 提出了一种以切片肌腱纤维软骨骨复合材料(TFBC)为载体的组织工程新方法 用于种植骨髓干细胞(BMSC)的支架，用于肩袖修复增强。我们的预赛 研究表明，该TFBC能机械地促进肩袖修复。TFBC可以重振旗鼓 通过种植BMSCs，在自然肌腱环境中表达机械载荷下的肌腱发生。我们的 最近的活体数据表明，我们设计的TFBC生物增强了肩袖修复 在我们新开发的手术后六周内，与单独修复或TFBC支架相比，效果更好 犬非负重肩部模型，模拟人体肩部功能和活动。基于我们的 初步研究，目前提案的总体目标是开发和测试一种功能 用于旋转撕裂治疗的工程化复合组织(TFBC)。我们的基本假设是我们的 工程化TFBC作为一种强化生物材料，将改善旋转术后的功能结果 袖带修复与临床使用的生物材料(GraftJacket)的比较。我们还假设TFBC将 帮助重建肌腱端部，这在目前一直是一个巨大的挑战 接近，因为TFBC包含一个天然的纤维软骨区。为了验证我们的假设，下面两个例子 提出了具体的目标。具体目标1是测试TFBC的机械增强性能 在体外模型中，TFBC用于肩袖修复。具体目标2是测试工程TFBC生物 犬在体模型中的强化和凹陷再生，并进行长期随访。我们预计会有两个 这项研究的重要成果：1)TFBC增强了旋转体的机械性能 2)工程化TFBC有效减少了肩袖修复失败，改善了肩袖 修复愈合，重建到目前为止还没有成功再生的肌腱端部。如果我们的 如果假设得到支持，我们将开发出一种新的、有效的、临床适用的生物材料来 提高肩袖修复质量，对肩袖撕裂领域有重大影响，a 具有挑战性的临床和研究问题。

PROJECT SUMMARY/ABSTRACT Rotator cuff tears are common, disabling, and are costly musculoskeletal injuries. Surgical repair is a common treatment, but recurrent tears occur in 20 to 90% of patients, especially in those with large or massive tears. Rotator cuff repair with biomaterial augmentations, including mechanical augmentation to increase the repair strength and biological healing to accelerate tissue regeneration, may reduce postoperative complications. However, the current graft materials used for augmentation are far from satisfactory. Tissue engineering offers the potential to generate functional tissue replacement, however, designing an appropriate scaffold that can has native tendon mechanical properties and provide an optimal environment for cell seeding, growth, and differentiation, especially for tendon enthesis regeneration, has proven challenging. In this application, we propose a novel tissue engineering approach using a sliced tendon fibrocartilage bone composite (TFBC) as a scaffold to seed bone marrow-derived stem cells (BMSC) for rotator cuff repair augmentation. Our preliminary studies indicated that this TFBC can mechanically enhance the rotator cuff repair. The TFBC can be revitalized by seeding BMSCs, which express tenogenesis in native tendon environment under mechanical loading. Our recent in vivo data demonstrated that our engineered TFBC biologically augmented the rotator cuff repair better when compared to repair or TFBC scaffold alone after six weeks post-surgery in our newly developed canine non-weight bearing shoulder model which mimics human shoulder function and activities. Based on our preliminary studies, the overall goal of the current proposal is to develop and test a functional engineered composite tissue (TFBC) for rotator tear treatment. Our underlying hypothesis is that our engineered TFBC, as an augmentation biomaterial, will improve functional outcomes following rotator cuff repairs compared to the clinically used biomaterial (GraftJacket). We also postulate that TFBC will help to rebuild the tendon enthesis, which has been a great challenge to regenerate in the current approaches, as the TFBC contains a native fibrocartilage zone. To test our hypothesis, the following two specific aims are proposed. Specific Aim 1 is to test the TFBC mechanical augmentation properties when the TFBC is used for rotator cuff repair in an in vitro model. Specific Aim 2 is to test engineered TFBC biological augmentation and enthesis regeneration in a canine in vivo model with a long-term followup. We expect two important outcomes from this investigation: 1) The TFBC strengthens the mechanical properties of the rotator cuff repair, and 2) the engineered TFBC effectively reduce the rotator repair failure, improve the rotator cuff repair healing, and rebuild a tendon enthesis which has not been successfully regenerate to date. If our hypothesis is supported, we would have developed a novel, effective, and clinically-applicable biomaterial to improve the quality of rotator cuff repairs, which has a significant impact on the field of rotator cuff tear, a challenging clinical and research issue.