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手术后常见的并发症。粘连会严重损害患指的功能和活动范围，并可能导致手功能的部分丧失。目前用于减少粘连的方法是注射透明质酸(HA)或插入由化学修饰的HA制备的屏障，但注射的HA或HA屏障的半衰期较短，影响了它们防止粘连的效果。为了解决这个问题，我们最近开发了一种新型的可原位交联的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，这种HA-MMC水凝胶的膜屏障和注射形式防止了大鼠子宫角模型腹膜内粘连的形成。我们现在建议建立使用这种材料的可行性，以解决肌腱外科中未得到满足的重要外科需求。该计划的最终目标是证明，可以通过一种复合材料减少或消除术后肌腱粘连，这种复合材料可以促进手术修复的肌腱愈合，同时防止与周围组织的粘连形成。这一目标将通过四个具体目标在实验中实现。首先，我们将制备不同浓度MMC的交联凝胶，并测定薄膜中MMC的释放速率。其次，我们将通过在啮齿类动物皮下注射原位可交联凝胶来确定其体内的生物相容性。第三，我们将使用HA-MMC材料来制备薄膜和管子。最后，我们将使用功能、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有效性。

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.