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Human induced pluripotent stem cell (hiPSC)-derived brain organoids can recapitulate the complex cytoarchitecture of the brain as well as the genetic and epigenetic footprint of human brain development. Although the brain organoids are able to mimic the structures and functions of brain in vitro, the 3D models have difficulty in integrating a complex vascular network that can provide the interaction with organoids. Here we report on a microfluidicbased three-dimensional, vascularized cortical organoid tissue construct consisting of 1) a perfused micro-vessel against an extracellular matrix (ECM), dynamic flow and membrane-free culture of the endothelial layer, 2) a sprouted vascular network using a combination of angiogenic factors, and 3) a vascularized hiPSCderived cortical organoid. We report on an optimization of density/stiffness of ECM to induce angiogenic sprouting and effect of angiogenic factors to trigger robust, rapid, and directional angiogenesis for concentration-driven and repetitive sprout formation. Vascularized network in the microfluidic device was further characterized in terms of morphology, directional alignment under perfusion, lumen formation, and permeability. HiPSCderived cortical organoid was generated, placed, and integrated into a vascularized network in the vascularized microfluidic device. We investigate how vascularized micro-vessels interact with cortical organoid. This paper further demonstrates the potential utility of a membrane-free vascularized cortical organoid in perfusion used to model Alzheimer’s disease and for toxicity screening of nerve agents.
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Stretchable Mesh Nanoelectronics for 3D Single‐Cell Chronic Electrophysiology from Developing Brain Organoids
Abstract Human induced pluripotent stem cell derived brain organoids have shown great potential for studies of human brain development and neurological disorders. However, quantifying the evolution of the electrical properties of brain organoids during development is currently limited by the measurement techniques, which cannot provide long‐term stable 3D bioelectrical interfaces with developing brain organoids. Here, a cyborg brain organoid platform is reported, in which “tissue‐like” stretchable mesh nanoelectronics are designed to match the mechanical properties of brain organoids and to be folded by the organogenetic process of progenitor or stem cells, distributing stretchable electrode arrays across the 3D organoids. The tissue‐wide integrated stretchable electrode arrays show no interruption to brain organoid development, adapt to the volume and morphological changes during brain organoid organogenesis, and provide long‐term stable electrical contacts with neurons within brain organoids during development. The seamless and noninvasive coupling of electrodes to neurons enables long‐term stable, continuous recording and captures the emergence of single‐cell action potentials from early‐stage brain organoid development.
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- Award ID(s):
- 2011754
- PAR ID:
- 10500425
- Publisher / Repository:
- Wiley
- Date Published:
- Journal Name:
- Advanced Materials
- Volume:
- 34
- Issue:
- 11
- ISSN:
- 0935-9648
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
-
Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1002/adma.202106829
