# Regulation of chondrocyte fate and function by ECM Viscoelasticity

> **NIH NIH R01** · STANFORD UNIVERSITY · 2023 · $617,693

## Abstract

Abstract
Osteoarthritis (OA) is a major disease affecting 1 in 6 adults above 60 years of age in US that significantly impairs
quality-of-life by impacting movement and function. Tissue health and disease is frequently governed by a
complex and non-linear interplay of cell-intrinsic and systemic factors including both biochemical and biophysical
cues. The overall aim of this project is to understand how the changes in ECM (extra cellular matrix)
viscoelasticity affect cartilage homeostasis in health and during disease initiation and pathogenesis in OA.
Recent studies by our team have elegantly demonstrated that ECM viscoelasticity governs cell volume in
cartilage cells i.e. chondrocytes. Previous studies of cartilage biology had only examined the impact of ECM
elasticity (i.e. “stiffness”), and the role of viscoelasticity had been mostly ignored. We found that viscoelastic
hydrogels that exhibit fast stress relaxation, or were more viscous, could provide a microenvironment that is
more conducive to anabolic gene expression in human chondrocytes resulting in increased ECM production,
promoting a healthy chondrocyte phenotype. The underlying cause was observed to be the ability of
chondrocytes to expand their volume in the fast relaxing gels, an ability that was restricted in the slow relaxing
gels, which are more elastic. Understanding the optimal ECM viscoelasticity for healthy and human induced
pluripotent stem cell derived chondrocytes can guide ideal scaffold preparation for cartilage tissue engineering.
The aim of this proposal is therefore to optimize hydrogel viscoelasticity for engineering inflammation-
suppressive cartilage constructs. We will firstly optimize development of cartilage constructs in fast relaxing
hydrogels in the presence of dynamic mechanical loading. Secondly, these constructs will be tested in human
and rat models of cartilage defects. Thirdly, we aim to gain an understanding of the molecular pathways
underlying the relationship between mechano-transduction and inflammation in cartilage health and disease.
The experimental outcomes from these studies have the potential to enhance therapeutic strategies for cartilage
regeneration and OA that remain unmet clinical needs.

## Key facts

- **NIH application ID:** 10751895
- **Project number:** 1R01AR081993-01A1
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Nidhi Bhutani
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $617,693
- **Award type:** 1
- **Project period:** 2023-09-01 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10751895

## Citation

> US National Institutes of Health, RePORTER application 10751895, Regulation of chondrocyte fate and function by ECM Viscoelasticity (1R01AR081993-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10751895. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*