# A Neurovascular Microphysiological System

> **NIH NIH R01** · UNIVERSITY OF WISCONSIN-MADISON · 2022 · $340,156

## Abstract

PROJECT SUMMARY/ABSTRACT
There has recently been a dramatic increase in incidences of neurodevelopment disorders (NDDs) in children.
For instance, autism spectrum disorders have increased from 1 in 2000 people in 1980s to the recently reported
1 in 68 as reported by the CDC. In addition, instances of primary microcephaly due to Zika virus exposure have
gained global attention, and birth defects caused by thalidomide and prenatal alcohol exposures highlight the
importance of developing suitable model systems to understand, detect, and treat causes of these disorders.
The importance of vascular tissue development and its contributions to disease pathologies are often overlooked,
as the focus is instead on the role of neural and glial cell types. However, a number of neurodevelopmental and
neurodegenerative disorders are directly associated with vascular malformations, including microcephaly,
cerebral cavernous malformations, autism, Alzheimer’s disease, Alexander’s disease, and Rett syndrome. The
developing brain is at its most vulnerable during the early stages of neurodevelopment, and one key point of
vulnerability is the initial vascularization of the developing brain from the associated perineural vascular plexus
(PNVP), where the blood brain barrier has yet to fully form. There is to date no human model that mimics the
brain vasculature at this critical stage. We propose to generate a neurovascular microphysiological system (NV-
MPS) that mimics the initial vascularization of the developing brain and to progress the model to support the long
term maintenance of an engineered reproducible brain organoid. The proposed studies will achieve three specific
aims. Specific Aim 1 will create a developing brain microphysiological system (MPS) using a tubeless
microfluidics device, synthetic hydrogels and human PSC-derived cell types. Specific Aim 2 will generate models
of a diseased developing brain and measure molecular, cellular and tissue level outputs that have been identified
to be indicators of perineural vascular plexus formation, neurovascular integration and subsequent cortical
maturation. Specific Aim 3 will measure and stimulate neuronal electrophysiological function in the NV-MPSs
using integrated cellular reporters and optically transparent embedded electrodes. Completion of this research
will provide a simple, robust and reliable NV-MPS that will provide the means to study the initial vascularization
of the developing brain, the neurovascular contributions to neurological disorders and a means to test the effect
of xenobiotic exposures at the early stages of neural development and finally will create a perfusable vasculature
that feeds and maintains engineered neural organoids.

## Key facts

- **NIH application ID:** 10465063
- **Project number:** 5R01NS109427-04
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** WILLIAM L. MURPHY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $340,156
- **Award type:** 5
- **Project period:** 2019-07-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10465063

## Citation

> US National Institutes of Health, RePORTER application 10465063, A Neurovascular Microphysiological System (5R01NS109427-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10465063. Licensed CC0.

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