# Engineering microscale hydrogel deposition to direct single stem cell differentiation

> **NIH NIH R01** · UNIVERSITY OF ILLINOIS AT CHICAGO · 2021 · $400,150

## 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:** 10181469
- **Project number:** 1R01GM141147-01
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT CHICAGO
- **Principal Investigator:** Jae-Won Shin
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $400,150
- **Award type:** 1
- **Project period:** 2021-04-01 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10181469

## Citation

> US National Institutes of Health, RePORTER application 10181469, Engineering microscale hydrogel deposition to direct single stem cell differentiation (1R01GM141147-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10181469. Licensed CC0.

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