Tuesday, February 17, 2026 2/17/2026

Engineered Asymmetric Hydrogel for Muscle Stem Cell Polarity and Fate Specification

Award Number: R01AR080616
ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 03/01/2022
PERIOD OF PERFORMANCE END DATE: 01/31/2027

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Engineered Asymmetric Hydrogel for Muscle Stem Cell Polarity and Fate Specification - ABSTRACT Skeletal muscle stem cell (MuSC) transplantation is emerging as a promising strategy for treating muscle- associated trauma and diseases. However, MuSCs spontaneously lose their “stemness” and engraftment potential in conventional 2D culture, critically limiting their applicability for cell-based therapy. This inability to culture MuSCs further limits the employment of cell engineering strategies, such as ex vivo gene editing patient derived cells. Thus, there is a critical need for a strategy to maintain and expand therapeutically potent MuSC ex vivo long-term. To date, MuSC culture systems that recapitulate the asymmetric MuSC niche, consisting of myofiber and basal lamina, required to establish cellular polarity, support physiologic cell division, and guide fate specification, do not exist. The contribution of active mechanical forces in modulating MuSC polarity, division, and fate specification also remains overlooked. We believe that establishing MuSC polarity is a requirement for supporting long-term symmetric expansion ex vivo through biochemical and biophysical means. To this end, the proposed research will engineer an asymmetric designer platform for expanding self-renewing MuSCs ex vivo long-term by directing cellular polarity and fate specification. In Aim 1, we will identify minimally essential asymmetric cues for establishing MuSC polarity by engineering an asymmetric hydrogel. In Aim 2, we will determine the effects of biochemically promoting symmetric cell division on long-term expansion of MuSCs using the asymmetric hydrogel. Biochemical strategies to inhibit asymmetric division and to promote symmetric division to achieve ex vivo MuSC expansion will be tested. In Aim 3, we will determine the effects of dynamic biomechanical stretch on regulation of symmetric MuSC expansion using the asymmetric hydrogel. Mechanisms by which externally applied forces align mitotic spindle orientation and regulate cell division of polarized MuSCs will be tested. Successful outcomes of this research will not only develop a platform for expanding MuSCs for cell therapies by directing stem cell polarity and fate specification but also provide establish a new paradigm for harnessing stem cell polarity in cell-instructive biomaterials for regenerative medicine.


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 = $409,831 )
2026	2026	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	1 GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	5	1/21/2026	NON-COMPETING CONTINUATION	$409,831
														Subtotal = $409,831

Issue Date FY: 2025 ( Subtotal = $409,831 )
2025	2025	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	1 GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	4	1/14/2025	NON-COMPETING CONTINUATION	$409,831
														Subtotal = $409,831

Issue Date FY: 2024 ( Subtotal = $543,167 )
2024	2024	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	1 GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	3	1/17/2024	NON-COMPETING CONTINUATION	$409,831
2024	2024	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	1 GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	002	3	5/29/2024	NON-COMPETING CONTINUATION	$31,875
2024	2024	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	1 GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	3	1/22/2024	SUPPLEMENT FOR EXPANSION	$101,461
														Subtotal = $543,167

Issue Date FY: 2023 ( Subtotal = $486,701 )
2023	2023	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	ONE GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	003	2	8/9/2023	SUPPLEMENT FOR EXPANSION	$42,274
2023	2023	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	ONE GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	004	2	8/25/2023	SUPPLEMENT FOR EXPANSION	$0
2023	2023	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	ONE GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	2	1/18/2023	NON-COMPETING CONTINUATION	$409,831
2023	2023	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	ONE GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	2	2/22/2023	NON-COMPETING CONTINUATION	$45,537
2023	2022	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	ONE GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	002	1	3/8/2023	SUPPLEMENT FOR EXPANSION	-$10,941
														Subtotal = $486,701

Issue Date FY: 2022 ( Subtotal = $496,097 )
2022	2022	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	ONE GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	1	9/22/2022	SUPPLEMENT FOR EXPANSION	$40,729
2022	2022	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	ONE GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	1	2/18/2022	NEW	$455,368
														Subtotal = $496,097

Grand Total All Awards = $2,345,627

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Engineered Asymmetric Hydrogel for Muscle Stem Cell Polarity and Fate Specification

Award Number: R01AR080616

ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 03/01/2022

PERIOD OF PERFORMANCE END DATE: 01/31/2027

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