Biomaterials for Adhesion-Free Tendon Repair

用于无粘连肌腱修复的生物材料

• 批准号: 7407741
• 负责人: GLENN DOWNES PRESTWICH
• 金额: $ 4.87万
• 依托单位: CARBYLAN BIOSURGERY, INC.
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-09 至 2006-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7407741
• 关键词: biomaterial compatibility; biomaterial development /preparation; biomaterial evaluation; biomaterial interface interaction; biotechnology; cell adhesion; cytoprotection; gel; hyaluronate; laboratory rabbit; mitomycin C; orthopedics; postoperative complications; slow release drug; surgery material /equipment; tendons; wound healing

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.

描述（由申请人提供）：手部屈肌腱手术后形成粘连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运动范围，并可能导致手部功能部分丧失。目前使用注射透明质酸 (HA) 或插入由化学修饰的 HA 制备的屏障来减少粘连，但注射的 HA 或 HA 屏障的半衰期较短，损害了其预防粘连的功效。为了解决这个问题，我们最近开发了一种新型原位可交联 HA 水凝胶，它可以通过共价连接含有抗增殖药物丝裂霉素 C (MMC)。初步结果显示，这种 HA-MMC 水凝胶的薄膜屏障和注射形式可防止大鼠子宫角模型中腹膜内粘连的形成。我们现在建议建立使用这种材料来解决肌腱手术中未满足的重要手术需求的可行性。该计划的最终目标是证明复合材料可以减少或消除术后肌腱粘连，从而促进手术修复肌腱的愈合，同时防止与周围组织形成粘连。这一目标将通过四个具体目标通过实验来实现。首先，我们将制备具有不同 MMC 浓度的交联凝胶，并测定 MMC 从薄膜中的释放速率。其次，我们将通过在啮齿类动物中皮下注射原位可交联凝胶来确定体内生物相容性。第三，我们将使用HA-MMC材料制造薄膜和管材。最后，我们将使用功能、生物力学和组织学标准确定这些 HA-MMC 装置在兔指屈肌腱模型中的功效。