Fabrication of vascularized organoids for regenerative medicine and drug discovery

器官修复和移植需求的不断增长，以及开发模拟天然器官复杂性的体外模型以用于药物发现的未满足需求，导致了一些创新，使类器官结构的生物工程成为可能。类器官是一种三维（3D）细胞培养物**，包含了所代表器官的一些关键特征，经常用于此类应用。**这些体外培养系统包含自我更新的干细胞群，这些干细胞群分化成多种器官特异性细胞类型，这些细胞类型表现出与相应器官相似的空间组织，并能够概括该器官的某些功能，从而提供一个高度生理相关的系统。然而，由于在较大的类器官中质量传输的限制，类器官的使用仅限于小尺寸（< 1mm）。尺寸大于几百微米的实验室工程组织需要内部血管供应以达到临床显著的活细胞密度。这个短期项目旨在开发毫米大小的人类诱导多能干细胞(hiPSCs)**，其微孔作为血管系统，以增强类器官结构内的质量运输。我们将使用微流体系统制造水凝胶微棒，在类器官形成过程中与细胞混合，并提供类似血管的结构，以增强类器官内氧气和营养物质的运输。我们将进行系统的表征研究，以制定微棒制造的方案，并将与STEMCELL技术合作将其纳入类器官。拟议的研究项目将为加拿大经济、加拿大在生命科学研究和创新方面的国际声誉以及加拿大人的生活质量带来许多深远的好处。此外，由于干细胞和再生医学这一快速发展的领域在全球范围内具有非常高的研发需求，因此必须在这些领域进行创新研究并培养人才，以确保加拿大在这些前沿领域保持领先地位。

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.