The Effect of Age on Functional ACL Healing

年龄对 ACL 功能愈合的影响

• 批准号: 7137003
• 负责人: Martha M Murray
• 金额: $ 37.18万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-01 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7137003
• 关键词: aging; cell migration; collagen; injury; knee; ligaments; model; osteoarthritis; surgery material /equipment; tear

DESCRIPTION (provided by applicant): Rupture of the anterior cruciate ligament (ACL) of the knee is an increasingly common injury in adolescents. Current treatment is ACL reconstruction where the torn ligament is removed from the knee and a tendon graft is placed through the knee to replace it. While this procedure is good at restoring gross stability to the knee, as many as 78% of patients will develop premature osteoarthritis of the knee 14 years after surgery. For the estimated 38,000 high school students who sustain this injury each year, this is a significant risk for permanent disability. Thus, new solutions for this injury are required, especially for young patients. Recent work in our laboratory has demonstrated that the ACL can be induced to heal if suture repair is supplemented with a collagen-platelet rich plasma hydrogel placed in the wound site. Stimulating healing of the ACL has several important advantages over replacement of the torn ligament: there is no required harvest of tendons from elsewhere in the knee, the proprioceptive fibers of the ACL are preserved, and the complex anatomy of the ligament is more closely restored. We anticipate that preserving the dynamic proprioceptive function and complex anatomy of the ligament will decrease the risk of osteoarthritis. However, it is unknown if children and adolescents will also be able to successully heal the ACL with this technique. In the work outlined in this proposal, the effects of skeletal maturity on the functional healing process for this injury is examined in four specific aims. In Specific Aim I, cell migration as a function of age is studied in a previously established in vitro model. In Specific Aims 2, the rates of cell migration into an acellular scaffold in vivo will be measured. In Specific Aim 3, the effect of age on the revascularization of an acellular scaffold in vivo will be evaluated using in vivo MRI as well as histomorphometry. In Specific Aim 4, the effect of age on the restoration of biomechanical strength, stiffness and knee laxity after ACL repair will be examined. CLINICAL RELEVANCE: Tears of the anterior cruciate ligament of the knee affect over 100,000 patients each year and current treatments do not prevent premature osteoarthrititis. New treatments are being developed, where the ligament is stimulated to heal instead of being replaced, and this project will enable us to determine whether children and adolescents will be good candidates for this new approach.

描述（由申请人提供）：膝盖前交叉韧带（ACL）破裂是青少年越来越普遍的损伤。当前的治疗方法是ACL重建，其中从膝盖上去除韧带撕裂，并通过膝盖放置肌腱移植物以取代其。虽然此过程擅长恢复膝盖的总稳定性，但多达78％的患者会在手术后14年出现膝关节过早的骨关节炎。对于每年估计受伤的38,000名高中学生来说，这是永久残疾的重大风险。因此，需要解决这种伤害的新解决方案，尤其是对于年轻患者而言。我们实验室的最新工作表明，如果缝合缝合修复添加到伤口部位中含有胶原蛋白血浆富的血浆水凝胶，则可以诱导ACL愈合。刺激ACL的愈合比替换裂缝具有多个重要优势：不需要从膝盖其他地方收获肌腱，ACL的前置纤维保留了，并且韧带的复杂解剖结构更加紧密地恢复。我们预计保留韧带的动态本体感受功能和复杂的解剖结构将降低骨关节炎的风险。但是，尚不清楚儿童和青少年是否也能够通过这种技术成功治愈ACL。在本提案中概述的工作中，骨骼成熟度对这种伤害功能愈合过程的影响在四个特定目标中进行了检查。在特定的目标I中，在先前建立的体外模型中研究了细胞迁移作为年龄的函数。在特定的目标2中，将测量细胞迁移到体内的细胞支架的速率。在特定的目标3中，将使用体内MRI和组织形态计量学评估年龄对体内卵巢支架血运重建的影响。在特定目标4中，将检查年龄对ACL修复后生物力学强度，刚度和膝关节松弛的恢复的影响。临床相关性：膝盖前交叉韧带的泪水每年会影响超过100,000名患者，而当前治疗并不能阻止过早的骨关节炎。正在开发新的疗法，刺激韧带以治愈而不是被替换，该项目将使我们能够确定儿童和青少年是否将成为这种新方法的好候选者。