Biomaterials for Adhesion-Free Tendon Repair

用于无粘连肌腱修复的生物材料

• 批准号: 6934414
• 负责人: GLENN DOWNES PRESTWICH
• 金额: $ 5.13万
• 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 2005-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6934414
• 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（由申请方提供）：手部屈肌腱手术后粘连形成是一种常见的术后并发症。粘连可严重损害受累手指的功能和活动范围，并可导致手功能的部分丧失。目前使用注射透明质酸（HA）或插入由化学改性的HA制备的屏障来减少粘连，但注射的HA或HA屏障的半衰期短，影响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的原位可交联的HA水凝胶，它可以通过共价键包含抗增殖药物丝裂霉素C（MMC）。在初步结果中，该HA-MMC水凝胶的膜屏障和可注射形式防止了大鼠子宫角模型中腹膜内粘连的形成。我们现在建议确定使用这种材料来解决肌腱手术中重要的未满足的手术需求的可行性。该计划的最终目标是证明，术后肌腱粘连可以通过复合材料减少或消除，该复合材料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进行实验。首先，我们将制备具有不同MMC浓度的交联凝胶，并确定MMC从膜中释放的速率。其次，我们将通过在啮齿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材料制备薄膜和管。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器械在兔指屈肌腱模型中的有效性。