# Injectable hydrogels for hiPSC-neuron therapy of spinal cord injury

> **NIH NIH K01** · STANFORD UNIVERSITY · 2024 · $168,296

## Abstract

PROJECT SUMMARY
 Regenerative medicine cell transplantation strategies are limited by poor transplanted cell survival,
retention, and integration. To overcome this, I propose development of an engineered biomaterial that addresses
two major causes of transplanted cell death: (i) acute membrane damage during injection and (ii) long-term
exposure to a toxic microenvironment, by providing (i) cell encapsulation within an injectable hydrogel and (ii)
slow-release of growth factors. To evaluate the preclinical effectiveness of this biomaterial, I will target cervical
spinal cord injury (SCI), which results in permanent sensorimotor dysfunction and has no clinically available
regenerative therapies. My data demonstrates that transplanting human induced pluripotent stem cell-derived
neurons (hiPSC-neurons) significantly improves anatomical and functional outcomes in rat models of cervical
SCI; however, this cell type suffers from poor transplanted cell viability, reducing therapeutic efficacy. I have
already shown that use of an injectable hydrogel significantly improves the acute viability of encapsulated cells
by providing mechanical shielding during injection, which resulted in statistically improved neurite outgrowth and
forelimb function. I now hypothesize that tuning the temporal growth factor-release properties of this designer,
injectable hydrogel will significantly improve long-term survival of transplanted hiPSC-neurons, leading to
significantly improved anatomical and functional outcomes. Specifically, in Aim 1, I will optimize a growth factor-
release system in vitro to assist hiPSC-neurons in surviving oxidative stress and excitotoxicity that are present
at the injury site. In Aim 2, I perform functional evaluation of this biomaterial/cell therapy in a subacute model of
SCI in comparison to standard delivery vehicles (saline and fibrinogen) and appropriate controls.
 My career goal is to lead a translational laboratory that leverages expertise in biomaterials and stem cell
biology to develop regenerative therapies for central nervous system (CNS) injury and to serve as a role model
for young female scientists from underrepresented backgrounds. This Career Development Award would enable
me to enhance my strong background in CNS neurodegeneration and stem cell biology with new expertise in
biomaterial design and translational bioengineering. My career development plan includes (1) formal
coursework in materials science and bioengineering, (2) technical training in recombinant biomaterials synthesis
and characterization, (3) close mentorship by an outstanding bioengineer with a strong track-record of successful
training and collaboration, and (4) career guidance by an Advisory Committee to prepare for my transition to
independence. My training plan leverages the outstanding resources available within Stanford University and
national and international events to strengthen my scientific network, build on my extensive mentorship and
grantsmanship...

## Key facts

- **NIH application ID:** 10885406
- **Project number:** 1K01EB033870-01A1
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Vanessa Madelyn Doulames
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $168,296
- **Award type:** 1
- **Project period:** 2024-06-14 → 2027-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10885406

## Citation

> US National Institutes of Health, RePORTER application 10885406, Injectable hydrogels for hiPSC-neuron therapy of spinal cord injury (1K01EB033870-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10885406. Licensed CC0.

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