# Investigating mechanical regulation of nephrogenesis using viscoelastic biomaterials and kidney organoids

> **NIH NIH F32** · HARVARD UNIVERSITY · 2022 · $67,174

## Abstract

PROJECT SUMMARY
Chronic kidney disease (CKD) affects ~15% of adults in the US and is associated with the irreversible loss of
nephrons, which form the basic functional unit of the kidney. There is currently no cure for CKD, and treatments
such as kidney transplantation and dialysis have a high morbidity and mortality. Developing strategies for
repairing or replacing nephrons will address this significant public health problem by providing an alternative
treatment for patients and a new model of kidney development and disease for drug screening.
Mechanical properties of the extracellular matrix, such as stiffness and viscoelasticity, regulate key aspects of
cell behavior that drive nephrogenesis in vivo, including proliferation, differentiation, and migration. However,
while the molecular mediators that drive nephrogenesis have been studied extensively, the role of matrix
mechanics in nephrogenesis remains unclear. Beyond elucidating the role of biomechanics in kidney
development, understanding the functional role of the mechanical microenvironment in nephrogenesis will help
to inform engineering strategies to reproduce nephrogenesis in vitro. The goal of this proposal is to integrate
3D viscoelastic alginate hydrogels and kidney organoids to test the hypothesis that the mechanical
microenvironment regulates nephrogenesis. The first aim is to determine the role of matrix stiffness and
viscoelasticity in the differentiation of human pluripotent stem cells into multipotent nephron progenitor cells and
the subsequent cellular organization of nephrons in kidney organoids. The second aim is to investigate how
hydrogel architecture affects the morphology and maturation of kidney organoids. These aims will be
accomplished by integrating bioengineering, biomaterials, developmental biology, computational modeling, and
mechanical characterization techniques.
Completion of this project will deepen our understanding of the role of the mechanical microenvironment in the
formation of nephrons and will fill a substantial knowledge gap regarding our fundamental understanding of
kidney development and stem cell differentiation in vivo. This work will also illuminate design principles for
engineering new biomaterials that support nephrogenesis in culture and the regeneration of nephrons in vivo.
The training will take place in the Mooney Lab at Harvard University in collaboration with the Mahadevan Lab at
Harvard University and the Bonventre Lab at Brigham and Women's Hospital. The training plan will enhance the
applicant’s skills in biomaterials design, quantitative biology, and kidney organoid culture and provide a broad
understanding of kidney development and disease.

## Key facts

- **NIH application ID:** 10536817
- **Project number:** 1F32DK134115-01
- **Recipient organization:** HARVARD UNIVERSITY
- **Principal Investigator:** Bryan Nerger
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $67,174
- **Award type:** 1
- **Project period:** 2022-08-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10536817

## Citation

> US National Institutes of Health, RePORTER application 10536817, Investigating mechanical regulation of nephrogenesis using viscoelastic biomaterials and kidney organoids (1F32DK134115-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10536817. Licensed CC0.

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