Vascularized organoid-on-a-chip for centimeter-scale organoid cultivation
X.Y. Gong, Yang Chen, Jianchen Peng, Xiao Ding, Hui Yang, A Wang, Emmanuel Enoch Dzakah, Bing Zhao
Abstract
An organoid is a three-dimensional (3D) cell culture model that can reproduce the distinct structure and inherent functionality of certain organs. Nevertheless, a major limitation of organoids is the absence of a complex vascular network, thus restricting the supply of oxygen and essential nutrients. Coupled with their inherent size constraints and metabolite accumulation, it is challenging for organoids to replicate the natural intricacies of organs, thereby limiting their applicability. To overcome the challenges associated with this technology, we developed a culture platform to cultivate tumors or organ-derived organoids up to the centimeter scale. Initially, a customized organoid-on-a-chip including a microvascular network at the micron scale was designed using 3D printing. Further, by integrating an infusion device, the chip ensures an adequate supply of nutrients and fluid immersion while mimicking blood flow dynamics. Our method overcomes the issue of the limited size of organ-oids due to insufficient nutrient access, making it possible to produce large-scale tumor and normal tissue models in vitro, while providing insights into drug efficacy and toxicology evaluation as well as standardized organoid production.