# Hydrogels with Tunable Stress Relaxation and Mobility for Enhancing Articular Cartilage Regeneration

> **NIH NIH F31** · STANFORD UNIVERSITY · 2023 · $47,694

## Abstract

Acute injury to articular cartilage is common and can significantly increase an individual’s risk for developing
osteoarthritis, yet effective regenerative therapies remain lacking. Cartilage has a limited capacity for self-
regeneration due to low cellularity and lack of vasculature. One promising strategy for cartilage repair is the use
of mesenchymal stem cells (MSCs). Injectable hydrogel carriers are particularly desirable for MSC delivery as
they can be applied to cartilage defects in minimally invasive procedures. Hydrogel design can be inspired by
native cartilage tissue properties such as stiffness and biochemical ligands, which have been extensively studied
in the context of MSC chondrogenesis in 3D. Cartilage is also viscoelastic, demonstrating stress relaxation
behavior in response to applied stresses. Using alginate hydrogels as a model system, it has been recently
shown that faster stress-relaxation enhances chondrocyte-based cartilage production. However, the way
viscoelasticity modulates MSC-based cartilage regeneration remains largely unknown.
Our lab has previously reported sliding hydrogels (SG) with mobile crosslinks that can slide along the PEG
polymer backbone, which significantly accelerated MSC chondrogenesis in 3D compared to non-mobile,
covalently crosslinked hydrogels. Unlike alginate hydrogels, SG is crosslinked by irreversible covalent bonds
and does not exhibit stress relaxation. Based on previous findings in both the SG and alginate hydrogel systems,
I hypothesize that introducing viscoelasticity to SG would further accelerate MSC-based cartilage regeneration
in a dose-dependent manner through enhanced mechanotransduction in vitro and in vivo. To test this hypothesis,
I propose to: (1) Develop and characterize adaptable sliding hydrogels (ASG) with tunable stress relaxation as
a 3D stem cell niche through the incorporation of dynamic crosslinks; (2) Evaluate the effect of stress relaxation
in ASG on MSC chondrogenesis in vitro and elucidate the underlying mechanisms by characterizing
mechanotransduction signaling; (3) Validate the efficacy of ASG with optimized stress relaxation in accelerating
MSC-based cartilage regeneration in vivo using a rat osteochondral defect model. Compared to alginate
hydrogels, the proposed PEG-based ASG is a cleaner system that presents cells with highly controlled niche
cues. The outcomes will fill a critical gap in knowledge about the way viscoelasticity influences MSC
chondrogenesis in 3D and pioneer the in vivo translation of dynamic hydrogels with viscoelasticity for cartilage
regeneration. I will be mentored by a team of basic and clinical scientists with complementary expertise in
biomaterials and tissue engineering, polymer chemistry, mechanotransduction, imaging and animal models. The
outcomes will fill a critical gap in knowledge about the way that viscoelasticity influences MSC chondrogenesis
in 3D and validate adaptable sliding hydrogels as a new biomaterial for accelerating M...

## Key facts

- **NIH application ID:** 10750831
- **Project number:** 1F31AR083254-01
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** SARAH JANE JONES
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $47,694
- **Award type:** 1
- **Project period:** 2023-09-15 → 2026-11-13

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10750831

## Citation

> US National Institutes of Health, RePORTER application 10750831, Hydrogels with Tunable Stress Relaxation and Mobility for Enhancing Articular Cartilage Regeneration (1F31AR083254-01). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10750831. Licensed CC0.

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