Developing Programmable Materials for Bioprinting

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Why and to whom the research is important: A multitude of events driving organogenesis, fibrosis, and cancer metastasis occurs in biochemical and biophysical mediated feedback loops that span the tissue, cellular, and biomolecular scale. Conventional tools to study biological phenomenon across these scales is challenging using conventional cell culture methods or small animal models due to limitations in the number of cells capable of being cultured in vitro or the physiological relevance of animal models relative to human tissues. 3D bioprinted models enable control of the initial placement of distinct cell types and hydrogel bioinks with specific chemical, biochemical, and mechanical characteristics. This DG program focuses on engineering soft bioactive materials capable of being bioprinted to develop cell-laden three-dimensional in vitro models that complement the existing methods while enabling researchers to probe the samples biochemistry and biophysical properties in real-time for extended periods. Expected outcomes: This research program is anticipated to generate new knowledge into the a priori selection of bioinks by evaluating the intrinsic mechanical properties of the materials in relation to their bioactivity. A class of bioinks that can be mechanically tuned by controlling the crosslinking density, or concentration, of a bioinert polysaccharide alginate in a formula that contains bioactive extracellular matrix molecules is expected to result in new in vitro models where cell growth, viability, and proliferation can be tuned. Finally, these bioinks will be engineered to contain externally addressable stimuli releasing materials that can initiate local stiffening or softening of the hydrogel scaffold to investigate the role mechanical heterogeneity plays in disease progression, fibrosis, or cell migration. The Long-term goal of my research program is to develop novel formulations of soft biomaterials capable of mimicking the physical and biological characteristics of native tissues using extrusion bioprinting. To advance this goal during the next five years the following specific objectives will be explored: (1) Quantitatively understand how intrinsic material properties impact printing and post-printing structural stability; (2) Develop methods to incorporate bioactive components into mechanically tunable bioinks; and (3) Engineer programmable materials that can be externally stimulated to undergo mechanical changes to mimic the biophysical environment during the epithelial-to-mesenchymal (EMT) transition. Expected Benefits: Developing a new alternative tool to conventional cell culture and animal models to probe fundamental biology will have a significant impact on the well-being of Canadians and provide researchers in the field with new tools to investigate problems that are currently difficult to assess. HQP trained in this research program will be leaders in the interdisciplinary field of bioprinting and tissue engineering.