# Engineering microscale hydrogel deposition to direct single stem cell differentiation

> **NIH NIH R01** · UNIVERSITY OF ILLINOIS AT CHICAGO · 2022 · $250,000

## Abstract

PROJECT SUMMARY
Adult stem cells hold broad-ranging clinical potential to regenerate injured tissues. For instance,
mesenchymal stem cells (MSCs) have been investigated in over 950 clinical trials for use in
many disease indications. Despite their significant clinical relevance, however, there is currently
lack of the mechanistic understanding to precisely control MSC functions for reproducible
therapeutic outcomes. Engineered hydrogels have been used to reveal the ability of MSCs to
sense and respond to matrix biophysical cues, which subsequently impact the differentiation
potential of MSCs. However, leveraging these insights for therapeutic purposes has been
challenging, since current approaches to interface a cell population with a hydrogel by
uncontrolled mixing overlook the significance of heterogeneity in the local amount of the gel
presented to individual cells, leading to variable and unclear cell-material interactions at the
single cell level. We describe herein a highly efficient approach to control microscale hydrogel
deposition around single cells in a 3D space independently of gel composition and elasticity.
Using this approach, our preliminary data show that MSCs rapidly expand in volume when they
adhere to an integrin ligand in thinner gels. We show that encapsulating single MSCs in a thin
gel coating is sufficient to enhance the osteogenic potential of MSCs even when gel elasticity is
low. We will build upon these results to test the hypothesis that controlling local gel deposition
around single MSCs impacts membrane tension and lineage specification by regulating cell
volume expansion. In Aim 1, we will determine the effect of varying local gel deposition on
regulatory volume decrease by modulating mechanosensitive ion channels and its impact on
membrane tension of MSCs. In Aim 2, we will determine how varied local gel deposition impacts
single MSC fate and MSC-based bone regeneration. We predict that there exists a
transcriptional program that is selectively activated when the gel deposition becomes thinner,
thereby impacting lineage specification of MSCs independently of gel elasticity. The project is
highly multidisciplinary in that it will employ a combination of expertise in biomaterials,
biophysical, genetic, and in vivo approaches to address the specific aims. The results will help
to define local gel deposition as an important determinant of stem cell growth, thereby impacting
stem cell mechanics and fate. Given the clinical relevance of these cells, our results will inform
formulation design of MSC-based therapeutics for improved regenerative outcomes.

## Key facts

- **NIH application ID:** 10582026
- **Project number:** 3R01GM141147-02S1
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT CHICAGO
- **Principal Investigator:** Jae-Won Shin
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $250,000
- **Award type:** 3
- **Project period:** 2021-04-01 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10582026

## Citation

> US National Institutes of Health, RePORTER application 10582026, Engineering microscale hydrogel deposition to direct single stem cell differentiation (3R01GM141147-02S1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10582026. Licensed CC0.

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