Grant: Operating Grant - PA: IMHA - New Invest.- Musculoskeletal Health Bridge Funding

Osteoarthritis (OA) causes pain and loss of skeletal function, impacting significantly the morbidity of the elderly (about 50% of Canadians over 60 years old suffer from OA). Articular cartilage, which protects bones from rubbing against each other at skeletal joints, is defective in OA. Total replacement of the affected skeletal joint with non-biological materials is the most common treatment for OA, but the surgery is very invasive and typically needs to be repeated at least once during the patient's lifetime. This proposal, a novel collaboration between a skeletal cell biologist and a bioengineer, develops novel biomedical engineering approaches to create cartilage tissue constructs as an alternate therapeutic avenue for OA sufferers. Tissue engineering aims to produce tissue constructs that can integrate biologically with the patient's own tissues, ultimately providing a permanent solution to repair damaged tissues. A major problem with articular cartilage repair is the fact that articular cartilage has different layers, or zones, each with characteristic mechanical and biological properties. As an engineering solution to this problem, we propose to use hybrid tissue constructs, which provide both the mechanical properties (e.g., using biodegradable polymers) and the biological properties (e.g., using hydrogels impregnated with cells) of the tissue of interest. Importantly, we vary the mechanical properties of the polymer to mimic different zones of articular cartilage. Simultaneously, we mimic zone-specific gene expression by genetically engineering the cells prior to incorporating them into the tissue constructs. We test the efficacy of these strategies both in tissue culture dishes and in living animals. Importantly, we develop completely novel strategies to evaluate the in vivo performance of cartilage tissue constructs, employing synchrotron imaging at our local resource, the Canadian Light Source.