Adhesive materials for tendon-to-bone repair

摘要 超过一半的老年人患有肩关节功能障碍和肩袖引起的疼痛 损伤，通常是一个或多个肩袖肌腱撕裂。手术修复肩袖是其中一个 最常见的整形外科手术，每年在美国进行超过250，000次修复 States.手术修复的目的是在断裂的肌腱和肌腱之间建立一个坚韧连接。 以恢复肩关节功能。不幸的是，健康的依恋系统并没有被重建， 目前基于缝合的手术技术，并且在愈合过程中不会再生，导致高失败率 手术后。这些失败主要是由于用于将肌腱固定到骨的修复技术; 代替如在健康附件中那样在宽的附件足迹区域上分布肌肉负荷， 手术修复将应力集中在少数缝线锚定点上。这些应力集中 导致缝线从肌腱中拔出，推动了分布技术的发展 应力远离缝线锚钉并穿过附件足迹。由于这个临床问题，我们 实施的模型和概念验证实验表明，机械优化的粘合剂 薄膜可以更好地将载荷分布在肌腱和骨之间的界面上， 肌腱-骨修复的负荷耐受性。在目前的项目中，我们提出了这一先前的理论和证明- 概念工作，以开发一种生物相关的粘合剂，用于增强肩袖修复。总体目标 是通过粘附性生物材料方法改善肌腱-骨外科修复结果。我们将采取 一种生物启发的方法来实现这一目标：粘合剂将模仿海洋生物粘附 生物化学具体而言，贻贝启发的儿茶酚衍生的粘合剂将使用体外和体内测试。 模型我们推测，儿茶酚衍生的粘合剂将增加初始修复强度和韧性 并允许改善腱-骨愈合。这将通过两个目标进行测试：目标1：发展贻贝- 具有用于肌腱-骨修复的适当机械性能的灵感儿茶酚衍生粘合剂， 体外评价其生物相容性。目的2：确定贻贝启发的儿茶酚衍生的化合物的功效。 用于改善体内肌腱-骨愈合的粘合剂。从长远来看，插入的粘合剂可以是 被修饰以携带生物活性因子和/或干细胞。除了要研究的机械增强之外 在目前的建议中，这些因素可能会进一步增强肌腱的长期愈合潜力， 骨附着

ABSTRACT More than half of the elderly population suffers from shoulder dysfunction and pain caused by rotator cuff injury, typically a tear of one or more of the rotator cuff tendons. Surgical repair of the rotator cuff is one of the most common orthopedic surgical procedures, with over 250,000 repairs performed each year in the United States. The goal of surgical repair is to create a strong and tough attachment between the ruptured tendon and bone in order to recover shoulder function. Unfortunately, the healthy attachment system is not recreated with current suture-based surgical techniques and is not regenerated during healing, leading to high failure rates post-operatively. These failures are primarily due to the repair techniques used to secure tendon to bone; instead of distributing muscle loads across a wide attachment footprint area, as in the healthy attachment, surgical repairs concentrate stress on a small number of suture anchor points. These stress concentrations lead to pullout of the suture from the tendon, motivating the development of technologies that distribute stresses away from suture anchors and across the attachment footprint. Motivated by this clinical problem, we implemented models and proof-of-concept experiments demonstrating that mechanically-optimized adhesive films can better distribute loads across the interface between tendon and bone and dramatically increase the load tolerance of a tendon-to-bone repair. In the current project, we advance this prior theoretical and proof-of- concept work to develop a biologically relevant adhesive for enhanced rotator cuff repair. The overall objective is to improve tendon-to-bone surgical repair outcomes through adhesive biomaterial approaches. We will take a bioinspired approach to achieve this goal: adhesives will be modeled after marine organism adhesion biochemistry. Specifically, mussel-inspired catechol-derived adhesives will be tested using in vitro and in vivo models. We hypothesize that catechol-derived adhesives will increase the initial repair strength and toughness and allow for improved tendon-to-bone healing. This will be tested across two aims: Aim 1: Develop mussel- inspired catechol-derived adhesives with appropriate mechanical properties for tendon-to-bone repair and evaluate their biocompatibility in vitro. Aim 2: Determine the efficacy of the mussel-inspired catechol-derived adhesive for improved tendon-to-bone healing in vivo. In the long term, the interposed adhesive could be modified to carry bioactive factors and/or stem cells. In addition to the mechanical augmentation to be studied in the current proposal, these factors may further enhance the long-term healing potential of the tendon-to- bone attachment.