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）：屈肌手术后的粘附形成是一种常见的术后并发症。粘连会严重损害受影响数字的运动功能和运动范围，并可能导致部分损失手部功能。目前使用注入透明质酸（HA）或用化学改性HA制备的屏障插入来减少粘附，但是，注射的HA或HA屏障的短半衰期损害了它们在预防粘附方面的功效。为了解决这个问题，我们最近开发了一种新型的原位交联HA水凝胶，该水凝胶可以通过共价链接含有抗增生性药物丝裂霉素C（MMC）。在初步结果中，这种HA-MMC水凝胶的膜屏障和可注射形式阻止了大鼠子宫角模型中腹膜内粘附的形成。现在，我们建议建立使用该材料来满足肌腱手术中重要的未经手术需求的可行性。该程序的最终目标是证明术后肌腱粘附可以通过复合材料降低或消除，该复合材料促进手术修复的肌腱的愈合，同时防止对周围组织的粘附形成。该目标将通过四个特定目标实验解决。首先，我们将准备具有不同MMC浓度的交联凝胶，并确定MMC从膜中释放的速率。其次，我们将通过皮下注射啮齿动物中的原位交联凝胶来确定体内的生物相容性。第三，我们将使用HA-MMC材料制造膜和管。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设备在兔数字屈肌模型中的功效。