# Decoupling Hydrogel Stiffness and Diffusivity for Hematopoietic Stem Cell Culture and Differentiation

> **NIH NIH R21** · UNIVERSITY OF TEXAS AT AUSTIN · 2024 · $186,172

## Abstract

PROJECT ABSTRACT
Hematopoietic stem cells (HSCs) in the bone marrow receive mechanical signals via adhesions to the
extracellular matrix and chemical signals from cytokines diffusing through the extracellular matrix. These two
signaling methods influence HSC survival, proliferation, and differentiation, with critical long-term effects on the
immune system and the body’s ability to maintain homeostasis. While in vitro studies using synthetic hydrogels
as artificial matrices have led to new insights on environmental control of HSC behavior, stiffness and solute
transport are highly correlated in synthetic hydrogels, so the mechanisms behind HSC responses to these
environments remain uncertain. The resulting uncertainty and limited control of hydrogel physical
properties may explain why robust methods for in vitro HSC expansion have not been established.
Therefore, the studies proposed here will fill a critical gap in hydrogel design capabilities and apply that new
knowledge to in vitro HSC culture. First, we will create a library of forty-five unique hydrogel formulations by
simultaneously manipulating three structural hydrogel synthesis parameters that our fundamental models have
predicted to create robust, independent variations in stiffness and solute transport. Second, we will culture HSCs
in a smaller, nine-formulation square matrix of hydrogel formulations with independently tuned stiffnesses and
solute transport profiles to decouple how the two physical hydrogel properties affect HSC survival, proliferation,
and differentiation. These studies will provide fundamental insight into HSC interactions with their physical
environment and identify physically optimized conditions for in vitro HSC culture.

## Key facts

- **NIH application ID:** 10810824
- **Project number:** 5R21HL165180-02
- **Recipient organization:** UNIVERSITY OF TEXAS AT AUSTIN
- **Principal Investigator:** NICHOLAS A PEPPAS
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $186,172
- **Award type:** 5
- **Project period:** 2023-04-01 → 2026-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10810824

## Citation

> US National Institutes of Health, RePORTER application 10810824, Decoupling Hydrogel Stiffness and Diffusivity for Hematopoietic Stem Cell Culture and Differentiation (5R21HL165180-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10810824. Licensed CC0.

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