Repair and Rehabilitation of Flexor Tendon Injury

描述（由申请人提供）：该项目的总体目标是通过开发影响肌腱滑动表面的疗法来改善肌腱修复的结果。在前两个资助期，我们表明外科医生可以通过改变缝合方法和术后治疗方案来减少肌腱修复后的粘连。这些变化已被纳入我们自己和其他中心的临床实践。在第三个资助期，我们探索了通过物理化学和药理手段进一步改善肌腱滑动和减少粘连的方法。这些研究表明，含有润滑糖蛋白（关节软骨中普遍存在的一种润滑糖蛋白）的工程肌腱表面涂层可以显著减少粘连，但在某些情况下，润滑处理过的肌腱的愈合过程会延迟。因此，在这个资助期，我们建议研究通过组织工程方法来保留润滑素的有益作用，同时改善内在肌腱愈合的方法。我们最近开发了一种植入骨髓源性基质细胞（BMSC）的间质胶原贴片，在体外似乎可以加速肌腱愈合。我们的中心假设是，这种BMSC种子贴片将提高肌腱在体内愈合的速度和强度，而不会对润滑增强修复和康复对肌腱滑动和粘连的有益影响产生不利影响。为了验证这一假设，我们制定了三个目标。目的1：在体外犬模型中，研究将BMSC种子、细胞因子增强的胶原贴片掺入修复部位后屈肌腱的愈合情况。目的2：研究骨髓间充质干细胞肌腱贴片联合表面修饰对犬体内屈指肌腱修复的影响。目的3是研究表面修饰和BMSC贴片对延迟肌腱康复方案的动物的影响。如果这些目标得以实现，我们相信这种双管齐下的组织工程方法可以发展成为一种临床方法，提供良好的、无粘连的肌腱修复。此外，这种方法可以在临床情况下提供减少粘连的好处，在早期运动不可能立即康复的情况下，例如在再植或其他复杂创伤的情况下，以及在幼儿或其他不合作的患者中。公共卫生相关性：肌腱损伤是常见的，往往是毁灭性的，导致永久性运动丧失。主要的问题是过多的疤痕，导致粘连，限制肌腱滑动。本项目旨在通过机械、物理化学和生物手段的结合来减少或消除粘连，从根本上重新设计损伤肌腱及其与周围组织的界面。

DESCRIPTION (provided by applicant): The overall goal of this project is to improve the results of tendon repair through the development of therapies that affect the tendon gliding surface. In the first two funding periods we showed that surgeons could reduce adhesions after tendon repair by changes in suture methods and postoperative therapy regimens. These changes have been incorporated into clinical practice in our own and other centers. In the third funding period, we explored means to further improve tendon gliding and reduce adhesions by physicochemical and pharmacological means. These studies have shown that adhesions can be dramatically reduced with an engineered tendon surface coating containing lubricin, a lubricating glycoprotein ubiquitous in articular cartilage, but in some cases the healing process in lubricin treated tendons is delayed. In this funding period, therefore, we propose to investigate methods to preserve the beneficial effects of lubricin while improving intrinsic tendon healing through a tissue engineering approach. We have recently developed an interpositional collagen patch seeded with bone marrow-derived stromal cells (BMSC) that appears to accelerate tendon healing in vitro. Our central hypothesis is that this BMSC seeded patch will improve the speed and strength of tendon healing in vivo, without adversely affecting the beneficial effects of lubricin-augmented repair and rehabilitation on tendon gliding and adhesions. To test this hypothesis we have developed three aims. Aim 1 is to investigate the healing of flexor tendons following the incorporation of BMSC seeded, cytokine augmented collagen patch into the repair site in a canine model in vitro. Aim 2 is to investigate the effects a BMSC tendon patch combined with surface modification on flexor tendon repair in a canine model in vivo. Aim 3 is to investigate the effect of surface modification and a BMSC patch on animals subjected to a postponed tendon rehabilitation protocol. If these aims are achieved, we believe that this two-pronged tissue engineering approach could be developed into a clinical method to provide sound, adhesion free tendon repairs. In addition, such an approach could provide benefits in reducing adhesions in clinical situations where immediate rehabilitation with early motion is impossible, such as in cases of replantation or other complex trauma, as well as in young children or other uncooperative patients. PUBLIC HEALTH RELEVANCE: Tendon injuries are common and often devastating, resulting in permanent loss of motion. The principal problem is excessive scarring, resulting in adhesions that limit tendon gliding. This project aims to reduce or eliminate adhesions through a combination of mechanical, physiochemical and biological means, fundamentally re-engineering the injured tendon and its interface with the surrounding tissues.