Clinically relevant large animal model of rotator cuff injury and repair

描述(由申请人提供)：项目摘要：在人类的情况下，慢性、全层肩袖撕裂而不进行手术修复会导致肌腱的永久性缺陷，卸载的肌肉会进展为严重的、不可逆转的萎缩和纤维化。没有现有的动物模型可以复制人类状况的这些关键方面。在大鼠肩部模型中，肌腱缺损可自行愈合，肌肉改变是可逆的。现有的大型动物肩部模型都没有囊膜切除，因此肌腱损伤是关节外的，并经历了自发的愈合。因此，我们认为需要一种新的动物模型，一种模拟人类情况的动物模型，包括关节囊损伤、没有自然愈合或瘢痕形成、肌肉萎缩、僵硬和脂肪堆积，以及控制术后康复的能力。因此，这项建议的目的是发展和验证一种具有临床相关性的慢性肩袖损伤和修复的动物模型。我们将在犬肩关节模型上进行冈下肌腱松解和关节囊切除。我们将进行三项独立的研究，我们认为这是实现我们的目标所必需的最低限度。这些研究的主要目的是：(1)证实肌腱松解和关节囊切除后没有自发愈合；(2)确定术后石膏固定对急性肌腱修复的影响；(3)确定6周慢性肌腱损伤的可修复性和可逆性。相关性：在成人人群中，慢性肩袖肌腱撕裂是发病率的常见原因。当保守治疗不能改善患者的症状时，手术修复慢性撕裂是必要的。然而，修复巨大的慢性袖口撕裂在20%-95%的病例中无法愈合，这构成了一个重大的临床问题。这一模型的成功开发将导致对影响这一常见临床问题结果的关键因素的重要研究，如手术技术、泪膜形态和时机。

DESCRIPTION (provided by applicant): Project Summary: In the human condition, a chronic, full thickness rotator cuff tear without surgical repair results in a permanent defect in the tendon, and the unloaded muscle progresses to severe and irreversible atrophy and fibrosis. There is no existing animal model that replicates these critical aspects of the human condition. In the rat shoulder model, the tendon defect undergoes spontaneous healing and the muscle changes are reversible. None of the existing large animal shoulder models have included capsulectomy, thus the tendon injury has been extra-articular and undergoes spontaneous healing. Therefore, we argue that a new animal model is needed, one that mimics the human condition with regard to joint capsule injury, the absence of spontaneous healing or scar formation, the presence of muscle atrophy, stiffening, and fat accumulation, and the ability to control post-operative rehabilitation. Thus it is the aim of this proposal to develop and validate a clinically relevant animal model of chronic rotator cuff injury and repair. We will perform infraspinatus tendon release together with joint capsule resection in a canine shoulder model. We will perform three separate studies, which we believe are the minimum necessary to address our aim. The primary objectives of these studies are to: (1) validate the absence of spontaneous healing after tendon release and joint capsule resection, (2) determine the influence of post-operative immobilization by casting on an acute tendon repair, and (3) determine the repairability and reversibility of a six-week chronic tendon injury. Relevance: Chronic rotator cuff tendon tears are a frequent cause for morbidity in the adult human population. Surgical repair of chronic tears is indicated when conservative treatment has failed to improve the patients' symptoms. However, repairs of large chronic cuff tears fail to heal in 20-95% of cases, posing a significant clinical problem. Successful development of this model would lead to important studies of critical factors thought to affect the outcome of this common clinical problem such as surgical technique, tear morphology and timing.