PROJECT SUMMARY/ABSTRACT
Human organoids are miniaturized model systems of organs produced by three-dimensional (3D) cultures of
tissue-resident-adult stem cells (ASCs) or pluripotent stem cells (PSCs) in vitro. They have emerged as a
promising platform for modeling tissue development and disease, personalized medicine development, drug
screening and drug toxicity investigations. Despite their great potential, current human organoids suffer from
immature structure and functionality, limited heterogeneity, as well as limited accessible readouts for organoid
evaluation. For example, detailed investigations of these 3D biosystems, such as 3D electrophysiological
mapping for brain and heart organoids, cannot be achieved using conventional approaches such as two-
dimensional (2D) multi-electrode arrays (MEAs) for modulation and multimodal sensing. Furthermore, most
current biosystems lack stable and mature vascularization that exists in vivo, which poses challenges to
controlled delivery of oxygen, nutrition, and molecules like neural patterning factors to enhance organoid size,
lifespan, and complexity. Our goal is to develop a soft electronic/microfluidic hybrid 3D network for online
monitoring, regulation, and vascularization of human organoids. The resulting system will integrate separately
addressable electrical, optical, electrochemical, and thermal sensors and stimulators of designated locations
with 3D biomimetic microvascular networks for simultaneous sensing, stimulation, and well-controlled delivery
of molecules into deep tissues to study tissue development and modulation. We will achieve this goal through
pursuing three specific aims: (1) Develop multifunctional 3D electronic networks with high spatiotemporal
resolution for online monitoring and regulation of organoid function, (2) Develop biomimetic 3D microvascular
networks for the vascularization of 3D tissues and integrate them with 3D electronic networks into a hybrid
system, and (3) Evaluate the efficiency and functional robustness of the integrated system in vitro using brain
organoids as an example. Our proposed multifunctional hybrid system incorporates the following notable
innovative features: 1) Soft, stretchable 3D networks for electrical, optical, electrochemical, and thermal sensing
and stimulation of human organoids, 2) Biomimetic 3D microvascular networks for the vascularization of human
organoids, 3) Fully integrated electronics and microfluidics networks as a micro-lab for investigating various
induced and natural behaviors of human organoids. This work will create a new route to study neurodevelopment
and neurological disorders through simultaneous monitoring, regulation, and vascularization of brain organoids
throughout their 3D interior, which is of broad potential interest to the neuroscience community. In addition, the
developed 3D hybrid system can be applied to other types of organoids, including heart, lung, and kidney for in
vitro studies of related diseases.
