Grant: Discovery Grants Program - Individual

Articular cartilage is the smooth connective tissue that covers the surfaces of bones in synovial joints, where it facilitates movement and force distribution. This load bearing tissue is characterized by a limited capacity for self-repair following injury, which has prompted the development of numerous strategies to engineer new cartilage for joint repair; however, the slow rate of tissue formation achieved by cells within biomaterials remains an important limitation of tissue engineering. The ability to accelerate cartilage tissue formation relies on ensuring a sufficient supply of energy to the cells to meet the demands associated with an increased cellular response. Bioenergetic materials are a novel class of material that can act to elevate energy levels in cells, thereby stimulating the rate of new tissue formation. The development of scaffolds from such materials would help stimulate the rate of tissue formation by cells and lead to the formation of large functional engineered tissues. The long-term goal of this research program is to develop novel strategies to produce functional cartilage tissues "in a lab" based on tissue engineering concepts. In this application, we propose to progress towards that goal by developing bioenergetic materials that can provide additional energy to the cartilage-forming cells to stimulate the rate of tissue formation. This will be achieved by delivering inorganic polyphosphate (polyP), an inorganic biopolymer increasingly linked to cellular bioenergetics, to cells at a controlled rate. The specific goals of our proposed research are (1) to develop nanomaterial that release polyP at a controllable rate, (2) to investigate the specific roles played by polyP in the processes by which chondrocytes produce energy, and (3) to incorporate polyP-based nanoparticles into bioinks specifically formulated to bioprint 3D engineered cartilage tissues. The development of novel bioenergetic materials for tissue engineering applications promises to improve our ability to engineer larger functional tissue constructs, addressing a major challenge in the field of tissue engineering. Furthermore, energy metabolism in normal chondrocytes is a topic of intense research activity; however, the bioenergetic roles of polyP in this tissue have yet to be studied. This research will thus also contribute to bridging that gap in our understanding. Taken together, this work will provide novel knowledge that can be applied to the development of advances in the restoration of healthy cartilage. Furthermore, this funding will support the development of up to 16 HQP including 4 graduate students, as well as undergraduate students. Through their work on these multidisciplinary projects, these trainees will acquire technical skills and develop critical thinking and creativity that can be applied to a career in biomedical engineering, to strengthen Canada's position in this sector, and are transferable to other fields.