# Combination of hiPSCs and bioengineering to repair injured pediatric brain

> **NIH NIH R01** · VIRGINIA COMMONWEALTH UNIVERSITY · 2020 · $420,147

## Abstract

Project Summary/Abstract
 Pediatric brain trauma is a significant debilitating health problem among children in the United States.
To date, there is no effective treatment to structurally repair the injured brain and restore the lost neurological
functions associated with brain trauma. Cell transplantation offers hope to treat the injured brain through direct
neural replacement to replenish cells lost to injury and reconstruct the disrupted neuronal circuitry or/and by
stimulating endogenous repair mechanisms. However, current approaches have encountered prominent issues
such as ethical controversies of cell source, limited cell availability, poor graft survival, lack of functional
integration of grafted cells, the risk of tumor formation and immunological rejection. Recent advances in tissue
engineering and induced pluripotent stem cells (iPSCs) have instilled new hope to develop patient-specific
autologous cell source to overcome the issues that neural transplantation has encountered. Utilizing iPSCs
and our well-constructed injectable hydrogel system, the goal of this proposal is to develop a biomaterial-
assisted cell transplantation strategy through modulating the host microenvironment to enhance brain structure
remodeling and improve survival, neuronal differentiation and functional integration of grafted cells achieving
repair and regeneration of the injured pediatric brain following traumatic injury. We have previously developed
a series of injectable in-situ cross-linkable hydrogels to promote the reconstruction of a complete vascular
network in the injured adult brain. We have also optimized our hydrogel system for supporting three
dimensional growths of cells and as a delivery vehicle releasing bioactive reagents. In this proposal, we plan
to utilize our hydrogel system to modify the host environment to promote long term survival, neuronal
differentiation and functional integration of the transplanted iPSC-derived neural stem cells (iPSC-NPs) in the
injured pediatric brain via reconstruction of a complete vasculature network and conditioning of focal tissue
microenvironment at the site of injury. We will test the central hypothesis that a combination of iPSCs
transplantation with targeted tissue bioengineering will achieve optimal brain tissue regeneration and enhance
functional recovery following pediatric brain injury. The hypothesis will be tests in two Specific Aims, 1)
Optimize the biomechanical and biochemical properties of our injectable hydrogel system to promote the
growth of primary neurons, endothelial cells isolated from neonatal brain and iPSC-NPs in vitro, 2) Utilize
injectable hydrogels optimized for neonatal brain cell growth to reconstruct local vasculature and deliver growth
promoting molecules in combination with iPSC-NPs to promote tissue structural regeneration and functional
recovery following pediatric brain injury. The results of this study will advance the understanding of the key
microenvironmental requirement...

## Key facts

- **NIH application ID:** 9944676
- **Project number:** 5R01NS093985-05
- **Recipient organization:** VIRGINIA COMMONWEALTH UNIVERSITY
- **Principal Investigator:** Dong Sun
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $420,147
- **Award type:** 5
- **Project period:** 2016-06-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9944676

## Citation

> US National Institutes of Health, RePORTER application 9944676, Combination of hiPSCs and bioengineering to repair injured pediatric brain (5R01NS093985-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9944676. Licensed CC0.

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