Biomaterials for Adhesion-Free Tendon Repair

描述（由申请人提供）：手部屈肌腱手术后粘连的形成是常见的术后并发症。粘连会严重损害受影响手指的功能和活动范围，并可能导致部分手部功能丧失。目前，注射透明质酸（HA）或插入由化学修饰的HA制备的屏障用于减少粘连，但注射的HA或HA屏障的半衰期较短，影响了其防止粘连的功效。为了解决这个问题，我们最近开发了一种新的原位交联HA水凝胶，它可以通过共价键含有抗增殖药物丝裂霉素C （MMC）。在初步结果中，膜屏障和注射形式的HA-MMC水凝胶阻止了大鼠子宫角模型中腹腔内粘连的形成。我们现在建议建立使用这种材料的可行性，以解决肌腱手术中重要的未满足的手术需求。该项目的最终目标是证明，通过一种复合材料可以减少或消除术后肌腱粘连，这种材料可以促进手术修复肌腱的愈合，同时防止粘连形成周围组织。这一目标将通过四个具体目标实验性地实现。首先，我们将制备不同MMC浓度的交联凝胶，并测定MMC从膜中的释放速率。其次，我们将通过皮下注射原位交联凝胶在啮齿动物体内测定生物相容性。第三，我们将使用HA-MMC材料制造薄膜和管。最后，我们将通过功能、生物力学和组织学标准来确定这些HA-MMC装置在兔指屈肌腱模型中的疗效。

DESCRIPTION (provided by applicant): The formation of adhesions following flexor tendon surgery in the hand is a common post-operative complication. Adhesions can severely impair the function and range of motion of the affected digit and can cause the partial loss of hand function. Injection of hyaluronan (HA) or insertion of barriers prepared from chemically-modified HA are currently used to reduce adhesions, but the short half-lives of injected HA or HA barriers compromises their efficacy in preventing adhesions. To address this problem, we recently developed a novel in situ crosslinkable HA hydrogel that can contain the antiproliferative drug mitomycin C (MMC) via a covalent linkage. In preliminary results, film barriers and injectable forms of this HA-MMC hydrogel prevented the formation of intraperitoneal adhesions in a rat uterine horn model. We now propose to establish the feasibility of using this material to address the important unmet surgical need in tendon surgery. The ultimate goal of this program is to demonstrate that post-operative tendon adhesions can be reduced or eliminated by a composite material that promotes the healing of the surgically repaired tendon while simultaneously preventing adhesion formation to surrounding tissues. This goal will be addressed experimentally through four specific aims. First, we will prepare crosslinked gels with different MMC concentrations and determine the rate of MMC release from the films. Second, we will determine the biocompatibility in vivo by subcutaneous injection of the in situ crosslinkable gels in rodents. Third, we will fabricate films and tubes using the HA-MMC materials. Finally, we will determine the efficacy of these HA-MMC devices in a rabbit digital flexor tendon model using functional, biomechanical, and histological criteria.