Friday, December 26, 2025 12/26/2025

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

Award Number: F31AR083254
ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 09/15/2023
PERIOD OF PERFORMANCE END DATE: 11/13/2026

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Hydrogels with Tunable Stress Relaxation and Mobility for Enhancing Articular Cartilage Regeneration - 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 MSC-based cartilage regeneration.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $49,538 )
2026	2026	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	3	12/16/2025	NON-COMPETING CONTINUATION	$49,538
														Subtotal = $49,538

Issue Date FY: 2025 ( Subtotal = $48,974 )
2025	2025	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	2	11/14/2024	NON-COMPETING CONTINUATION	$48,974
														Subtotal = $48,974

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2023	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	1	6/18/2024	NEW	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $47,694 )
2023	2023	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	1	8/2/2023	NEW	$47,694
														Subtotal = $47,694

Grand Total All Awards = $146,206

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

Award Number: F31AR083254

ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 09/15/2023

PERIOD OF PERFORMANCE END DATE: 11/13/2026

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