Grant: Discovery Grants Program - Individual

Biomaterial development is an iterative process that typically relies upon in vitro assessment of material propertie, such as degradation, drug release, bioconjugate activity and biocompatibility, to select and optimize candidate materials. The top candidates are tested in small mammalian models to assess the material performancein vivo. It is well recognized that in vitro models, although cost effective and simple, cannot recapitulate the in vivo environment and often materials that performed well in vitro fail or have unanticipated responses in vivo. However, it is not feasible to incorporate the current small animal models early in material development due to the significant resources that are required for animal work. Furthermore, while mammalian models provide important insights into outcomes of host responses and biomaterial performance, the endpoint data provide limited insight into the processes that contribute to the overall material performance.Recently, zebrafish have emerged as a powerful and robust animal model due to their small size, optical transparency, ease of genetic manipulation and their amenability to high-resolution, non-invasive image-based analysis of biological processes. Despite these numerous advantages, zebrafish have had very limited use in the field of biomaterials. The long-term vision of my proposed research program is to establish a zebrafish biomaterial-screening platform capable of rapid, predictive and cost effective in vivo characterization of biomaterials to improve the selection and optimization of candidate materials for biomedical applications. To achieve this long-term goal, three research objectives will be addressed over the next five years, and will train 2 MASc, 2 PhD and 4 undergraduate students:Objective 1: The development of a zebrafish biomaterial-screening platform by defining critical parameters and techniques for biomaterial micro-implantation that yield reproducible experimental conditions for evaluating biomaterial characteristics in zebrafish.Objective 2: Design zebrafish-based biomaterial characterization assays using non-invasive fluorescent microscopy techniques to evaluate microparticle degradation and drug release kinetics.Objective 3: Develop a biomaterial host response screening assay using transgenic zebrafish strains with fluorescently labelled cell populations to model general biomaterial host responses that may adversely affect biomaterial performance, including inflammation, calcification and fibrous encapsulation.The proposed research will have significant impact the fields of biomaterials and biomedical engineering by developing novel tools for in vivo biomaterial characterization that will enable the selection of better material candidates with well-predicted clinical performance.