Cartilage Mechnobiology

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Articular cartilage is a dense connective tissue that almost exclusively provides a mechanical role in synovial joints. Due to native cartilage’s relative inability for self-repair, substantial efforts have been placed on the development of engineered cartilage for joint resurfacing. However, as the engineered tissues are typically inferior to native cartilage, one strategy to enhance tissue properties is through the application of mechanical loading during tissue growth. Although widely adopted, the actual response of cartilage cells (chondrocytes) to mechanical stimuli is quite limited. The major factors that contribute to this limited cellular response are: (i) only a fraction of the cells appear to directly respond to the stimulus; and (ii) chondrocytes tend to rapidly desensitize under prolonged loading. The long-term goal of my NSERC funded research program is to improve the responsiveness of chondrocytes to mechanical loading, ultimately leading to the development of superior engineered cartilage. To achieve this goal, the short-term objectives of this research program are to: (i) investigate the mechanisms responsible for the heterogenic response of chondrocytes to mechanical loading; (ii) investigate the mechanisms responsible for load-induced chondrocyte desensitization; and (iii) develop new stimulation methods to improve cellular sensitivity. The proposed research is expected to make significant contributions to the discipline of Biomechanical Engineering by furthering our knowledge of the heterogenic and desensitization responses of cartilage cells to mechanical loading — areas which have not yet been studied. The ability to improve cellular sensitivity to mechanical stimuli has direct industrial applications towards the development new methods and devices for mechanobiology research. Similarly, improved methodologies are needed to create functional, load-bearing tissues suitable for cartilage repair and reconstruction. Over the next five years, this research program will also prepare 9 HQP (2 PhD, 3 MASc, and 4 undergraduates) for professional careers in biomedical engineering. HQP working on these projects will have the opportunity to be involved in interdisciplinary research and to acquire fundamental knowledge and practical experience in the areas of cellular mechanobiology and tissue engineering.