Grant: Discovery Grants Program - Individual

Articular cartilage is a dense, load bearing connective tissue that provides the sliding surfaces of synovial joints. Due to native cartilage's relative inability for self-repair, substantial efforts have been placed on the development of engineered (or lab grown) cartilage. Despite the potential of this approach for cartilage repair, a major shortcoming is low capacity of cartilage cells (chondrocytes) to generate significant quantities of tissue suitable for joint resurfacing. While different strategies have been investigated, a novel approach is to control nutrient metabolism. Although known for their anaerobic metabolism, chondrocytes synthesize more tissue under conditions that elicit mixed aerobic-anaerobic metabolism. Recently, we have demonstrated that this metabolic switch can induce specific signaling pathways that result in improved tissue growth. The long-term goal of this NSERC funded research program is to develop methods to improve the generation of functional engineered cartilage. Within this framework, the immediate goal over the next five years of this research program is to exploit these newly identified metabolic-signaling pathways to develop scalable processes to generate tissue engineered cartilage. To achieve this goal, a combination of experimental and computational approaches will be carried out through four parallel, but related objectives, as follows: (i) bioreactor control of the ATP-purinergic receptor pathway, (ii) bioreactor control of the HIF-1a pathway, (iii) effect of switching between discrete metabolic states on tissue growth, and (iv) development of growth-factor free approaches for chondrogenic stem cell differentiation. The proposed research is expected to make significant contributions to the discipline of Materials and Chemical Engineering (ENC04: Biomaterial Engineering; ENC02: Process Engineering) by creating effective processes for development of tissue engineered cartilage as well as furthering our knowledge of cartilage cell metabolism - an area which has generally received little attention. While improved methodologies are needed to create functional tissues suitable for cartilage repair and reconstruction, the development of scalable processes for cartilage tissue engineering and chondrogenic stem cell differentiation have direct industrial applications. Over the next five years, this research program will also prepare 8 HQP (4 PhD and 4 undergraduates) for professional careers in biochemical/biomedical/biomaterials 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 tissue engineering, metabolomics and metabolic modeling, and bioreactor control strategies.