Cerebral organoids offer a great opportunity to model human brain development and neurological diseases. However, current in vitro cerebral organoid system lacks the vascular network that exists in vivo. Without the vasculature, the cerebral organoids that mimic the early brain eventually become necrotic in their core. At that stage, vasculature is essential for the supply of oxygen and nutrients to improve the survival of the organoid tissue. Therefore, this thesis emphasizes the engineering of a functional and perfusable vascular network in a multiculture microfluidic platform, with the ultimate goal of integrating it with the cerebral organoid.

Several microfluidic approaches have made significant progress towards the formation of functional and perfusable vasculatures. None...[ Read more ]

Cerebral organoids offer a great opportunity to model human brain development and neurological diseases. However, current in vitro cerebral organoid system lacks the vascular network that exists in vivo. Without the vasculature, the cerebral organoids that mimic the early brain eventually become necrotic in their core. At that stage, vasculature is essential for the supply of oxygen and nutrients to improve the survival of the organoid tissue. Therefore, this thesis emphasizes the engineering of a functional and perfusable vascular network in a multiculture microfluidic platform, with the ultimate goal of integrating it with the cerebral organoid.

Several microfluidic approaches have made significant progress towards the formation of functional and perfusable vasculatures. Nonetheless, these approaches suffer from the issues of variability from both the hydrogel and endothelial cells as well as the requirement of specific working conditions. Adjustments are still required for different microfluidic designs. In this work, we demonstrated the formation of a vascular network and the establishment of open lumens in our device, based on a published approach. Throughout the study, we also identified the importance of input parameters in influencing the morphological characteristics of the vascular network. We then further characterized the vascular network formed by doing permeability and perfusion studies to exhibit its physiologically relevant barrier function and flow capabilities. In summary, we have presented a detailed study for the construction of a three-dimensional human vascular network in our current microfluidic device.