# Synthetic hydrogels to study formation and maintenance of intestinal crypts

> **NIH NIH R01** · UNIVERSITY OF COLORADO · 2021 · $399,456

## Abstract

ABSTRACT
Intestinal organoid models hold great promise as a tool to study intestinal development and disease, screen drug
candidates, or even produce transplantable tissue in vitro. Current culture methods for growth of intestinal
organoids rely almost exclusively on Matrigel, but Matrigel’s loosely-defined and variable composition makes
clinical translation nearly impossible and obstructs fundamental investigations into the role of key matrix factors
on organoid formation. While intestinal stem cells (ISCs) grown in Matrigel have a tremendous capacity for self-
organization into functionally sophisticated intestinal organoid structures, the self-organization principles are also
responsible for introducing variability and stochastic organoids that also differ from the native organ in multiple
aspects. In the proposed research, we aim to develop tunable hydrogel matrices for ISC expansion, colony
formation, and differentiation to form crypts. Unique to our materials is the ability to regulate the ISC
microenvironment spatiotemporally using photochemical reactions, and we propose to use photoadaptable
hydrogels to test hypotheses related to ISC mechanosensing and its effects on organoid growth (Aim 1); the role
of local matrix stiffness on organoid shape, cell proliferation, and crypt formation (Aim 2); and the plasticity of
crypt cells during their response to a stress or injury (Aim 3). We hypothesize that exogenous control of matrix
properties can be used to support efficient ISC organoid growth, and subsequently mimic cell-mediated crypt
formation and remodeling. The proposed material systems will allow us to not only study and direct the formation
of the crypt-villus architectures that are physiologically relevant, but also test maintenance of these structures in
response to dynamic changes in matrix properties corresponding to developmental processes, as well as crypt
regeneration after injury. Specifically, we propose to: 1. Investigate the role of matrix mechanical properties
and signaling on intestinal stem cells (ISCs) and their growth into spherical organoids. 2. Understand how
spatial changes in hydrogel mechanics permit ISCs to undergo progenitor commitment and subsequent
differentiation into functional cell types. and 3. Investigate the role of uniform and spatially variant cell-matrix
interactions on the de-differentiation of lineage specific epithelial cells and crypt regeneration after injury.

## Key facts

- **NIH application ID:** 10164770
- **Project number:** 5R01DK120921-03
- **Recipient organization:** UNIVERSITY OF COLORADO
- **Principal Investigator:** KRISTI S. ANSETH
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $399,456
- **Award type:** 5
- **Project period:** 2019-08-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10164770

## Citation

> US National Institutes of Health, RePORTER application 10164770, Synthetic hydrogels to study formation and maintenance of intestinal crypts (5R01DK120921-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10164770. Licensed CC0.

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