ACCELERATING RECOVERY FROM SOFT TISSUE INJURY USING IGFI

软组织损伤约占所有损伤的45% 在美国，肌肉骨骼损伤(MS)占所有与工作相关的伤害的43% 伤害，以及90%的与运动有关的伤害。急诊治疗有 一般侧重于限制进一步的组织损伤(通过初始 固定期)，限制炎症(通过结冰和抬高 该地区)，以及药物控制疼痛和炎症 (含阿司匹林和泰诺)。类固醇和非类固醇抗肿瘤药 发炎药已被认为是更有效的限制 炎症，但有证据表明，它们可以干扰两者 短期和长期的治愈。这些治疗指南反映了 急性损伤处理的主要经验性方法 解决症状，而不是原因。对这些疾病的生物治疗 损伤代表了积极操纵机制的可能性。 治愈的力量。我们建议胰岛素样生长因子-I(IGF-I)， 对MS生长、发育和修复中的所有细胞类型都是必不可少的， 是一种潜在的用于软组织的生物疗法 修理。我们的假设是：(1)IGF-I减弱损伤并调节 MS软组织愈合跨越了一系列急性软组织损伤， 加速恢复功能；(2)IGF-I调解局部 损伤后给药时的炎症反应，从而操纵 早期愈合过程；(3)IGF-I改善关节的机械状态 软组织损伤，包括中晚期愈合期。我们 将在我们的软组织模型中对这些假设进行实验测试 大鼠跟腱，通过：(1)扩展我们目前的实验模型 肌腱横切来模拟其他级别的组织损伤， 描述了IGF-I治疗产生的损伤范围 有益的功能结果；(2)生化和组织学 描述局部影响愈合的炎性阶段 IGF-I管理，记录TNF-α、IL-I、PGE2的变化 产生以及巨噬细胞和中性粒细胞的侵袭； 表征粘弹性材料性能的愈合 IGF-I治疗后的肌腱组织。使用外源性IGF-I治疗 减轻炎症相关的损伤，并促进以后 愈合参数代表了肌腱修复的一种创新方法 尤其是与目前的经验性治疗相比，这些治疗实际上阻止了 当地生产IGF-I等合成代谢产品。这些研究 旨在为临床的启动奠定基础 对肌肉骨骼软组织修复有潜在影响的试验 从财务和生活质量的角度来看。

Soft tissue injuries account for approximately 45 percent of all musculoskeletal (MS) injuries in the US, 43 percent of all work-related injuries, and 90 percent of sports related injuries. Acute treatment has generally focused on limiting further tissue damage (through an initial period of immobilization), limiting inflammation (by icing and elevating the region), and pharmacologically controlling pain and inflammation (with aspirin and Tylenol ). Steroidal and nonsteroidal anti- inflammatory agents have been proposed as more potent means of limiting inflammation, but there is evidence that they can interfere with both short and long-term healing. These treatment guidelines reflect a predominantly empirical approach to acute injury management which addresses symptoms, not causes. Biological treatments for these injuries represent the potential to positively manipulate the mechanisms of healing. We propose that insulin-like growth factor-I (IGF-I), essential for all cell types in MS growth, development and repair, represents a potential biological therapeutic for use in soft tissue repair. Our hypotheses are: (1) IGF-I attenuates damage and modulates MS soft tissue healing across a spectrum of acute soft tissue injuries, accelerating a return to function; (2) IGF-I mediates the local inflammatory response when administered post-injury, thus manipulating the early healing process; (3) IGF-I improves the mechanical state of a soft tissue injury, both intermediate and late healing periods. We will experimentally test these hypotheses in our soft tissue model, the rat Achilles tendon, by: (1) extending our current experimental model of tendon transection to simulate additional grades of tissue injury, delineating the range of injury for which IGF-I treatment produces a beneficial functional outcome; (2) biochemically and histologically characterizing the inflammatory phase of healing as affected by local IGF-I administration, documenting changes in TNF-alpha, IL-I, PGE2 production as well as macrophage and neutrophil invasion, and; (3) characterizing the viscoelastic material properties of the healing tendon tissue following IGF-I treatment. Using exogenous IGF-I to attenuate inflammation associated injury as well as to promote later healing parameters represents an innovative approach to tendon repair especially compared to current empirical treatments which actually block the local production of anabolic products such as IGF-I. These studies are designed to form the foundation for the initiation of clinical trials with potential to impact musculoskeletal soft tissue repair from both financial and quality of life standpoints.