# Synthetic hydrogels for biomanufacturing of iPSC-derived neural cells for precision medicine

> **NIH NIH R44** · STEM PHARM, INC. · 2021 · $678,585

## Abstract

Human neural cells manufactured using patient-derived induced pluripotent stem cells (iPSCs) hold great
promise for modeling neurodevelopmental disorders, discovering new precision therapies, and screening for
potential risks from environmental toxins 1-4. There have been significant advances in the last decade in protocols
and commercial media systems developed for differentiation into specific neural cell types 5-8. However, there
remain significant technical challenges to overcome in their generation, manufacturing and assay workflows.
iPSCs are typically differentiated on animal-derived substrates that introduce intrinsic variability and lack control
over mechanical stiffness and biochemical composition. This often results in low yields and high variability, which
may be more pronounced when generating cellular models of diseases. There is a critical need to develop
commercial tools that promote differentiation of iPSCs into mature neural cells in a controlled, efficient, and
reproducible fashion and that eliminate animal derived products. The resulting cells, associated cell-based
assays and cellular therapeutics will have a transformative impact on neural disease modeling, drug and
therapeutic discovery and toxin screening.
 Our Phase I study identified chemically defined and robust synthetic hydrogels for efficient differentiation
of iPSC-derived neural progenitor cells (NPCs) into cortical neurons and subsequent maturation to post-mitotic,
functionally mature neurons. The highly innovative aspects of this work are that the substrates are employed as
thin hydrogel coatings using our proprietary surface-localized polymerization methods which provides several
technical and commercialization advantages. In order to bring these novel substrates to market we propose the
following specific aims for our Phase II proposal: Specific Aim 1 will further validate the work that demonstrated
our optimized synthetic thin hydrogel coatings support neural differentiation and maturation. Including further
functional characterization of cells cultured on the substrates by employing microelectrode array analysis and
differential transcriptional analysis to compare cells cultured on the substrate. We will characterize of the physical
and mechanical properties of the optimized thin hydrogels and develop methods for coating plates using
automated systems. Specific Aim 2 will apply the substrates in a Proof-of-Concept demonstration utilizing the
substrates to assess cortical neurons from Major Depressive Disorder patient-derived samples compared with
controls. Specific Aim 3 will expand the technology platform by optimizing coating techniques on microcarriers
suitable for bioreactor scaling, which is a critical step to demonstrate these substrates are applicable to
biomanufacturing applications. This work is significant, as there is a critical need for better tools to optimize yields
and reduce variability in the differentiation of iPSCs to defined neural subtype...

## Key facts

- **NIH application ID:** 10237392
- **Project number:** 5R44NS102088-03
- **Recipient organization:** STEM PHARM, INC.
- **Principal Investigator:** Connie S Lebakken
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $678,585
- **Award type:** 5
- **Project period:** 2018-09-15 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10237392

## Citation

> US National Institutes of Health, RePORTER application 10237392, Synthetic hydrogels for biomanufacturing of iPSC-derived neural cells for precision medicine (5R44NS102088-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10237392. Licensed CC0.

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