Fabrication of vascularized organoids for regenerative medicine and drug discovery

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The ever-increasing demand for organ repair and transplantation and the unmet need for developing in vitro**models that mimic the complexities of native organs for drug discovery have led to several innovative that**enable the bioengineering of organ-like constructs. Organoids, which are three-dimensional (3D) cell cultures**that incorporate some of the critical features of the represented organ, are frequently used for such applications.**These in vitro culture systems contain a self-renewing stem cell population which differentiates into multiple,**organ-specific cell types that exhibit spatial organization similar to the corresponding organ and are capable of**recapitulating some functions of that organ providing a highly physiologically relevant system. However, the**use of organoids has been limited to small dimensions (<1 mm) due to the limitations imposed by mass**transport in larger organoids. Laboratory-engineered tissues with dimensions greater than a few hundred**micrometers require an internal vascular supply to attain clinically significant viable cell densities. This**short-term project aims to develop millimeter size organoids of human induced pluripotent stem cells (hiPSCs)**with micropores as vasculatures for enhanced mass transport within the organoid structure. We will use a**microfluidic system to fabricate hydrogel micro-rods that will be mixed with the cells during the organoid**formation and will provide a vascular-like construct that will enhance the transport of oxygen and nutrients**within the organoid. We will perform a systematic characterization study to develop a protocol for the**fabrication of the micro-rods and will incorporate them in organoids in collaboration with STEMCELL**technologies. The proposed research program will result in numerous and far-reaching benefits concerning the**Canadian economy, Canada's international reputation for life science research and innovation, and the quality**of Canadian's life. Moreover, as the rapidly growing fields of stem cells and regenerative medicine have a very**high research and development demand globally, it is essential to conduct innovative research and train**personnel in these areas, ensuring that Canada remains a leader in these cutting-edge fields.