THESIS
2019
xiii, 58 pages : color illustrations ; 30 cm
Abstract
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...[
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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.
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