Development of In Vitro Compression-Induced Rotator Cuff Injury Model: Aging and Inflammation in Tendon Degeneration

点击翻译按钮获取中文摘要

PROJECT SUMMARY The long-term goal of this project is to understand age-related biological changes negatively impact tendon mechanosensation and extracellular matrix remodeling. This application lays out a strategy to understand mechanistically the consequences of an increased compressive loading environment on tendon function, specifically as it relates to age-related rotator cuff degeneration. The central hypothesis of the proposal is that the chronic inflammatory environment and other age-related changes in tenocyte processes, combined with an increase in compressive loading due to poor posture and musculature, may lead to tendon degeneration. We will first harness our in vitro culture models along with incubator-housed controllable loading bioreactors to create compression-induced tendon damage in tendon explants. Specifically, we are building the first-of-its-kind dual axis mechanical loading bioreactor for tendon explant tissue to apply simultaneous tensile and compressive loading to samples. Using this bioreactor, we will establish models of compression- induced damage by varying loading duration (acute versus chronic) and maximum strain level (low and high). We will then use these models to decouple the contributions of natural aging and inflammation in the development of tissue damage. The project outlined in this application combines fundamental basic research importance with translation directed toward the future diagnosis and therapeutic treatment of early stage tendon degeneration. If successful, this work will fully decouple the effects of inflammation and mechanical overload on age-associated tendon degeneration. Furthermore, this model system can be used in the future to identify cellular pathways involved in aging which alter the response of tenocytes to loading, and to identify anti-aging therapies which may be more effective in preventing load-induced tendon damage in aged populations.