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.
