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Regenerating Hyaline Cartilage Using Nanofibrous Hollow Microspheres and Synergizing TGF-beta and HIF

Award Number: R01AR075770
ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Regenerating Hyaline Cartilage Using Nanofibrous Hollow Microspheres and Synergizing TGF-beta and HIF - Traumatized and diseased joint cartilage is the leading cause of disability, afflicting 33% of the adult population. State-of-the-art treatments for destroyed joint cartilage are seriously limited. Tissue engineering has this far failed to regenerate high-quality cartilage and prevent subsequent cartilage hypertrophy and degeneration. We have developed biodegradable nanofibrous hollow microspheres (NF-HMS) as a novel injectable carrier for chondrocytes and successfully regenerated high-quality cartilage. To circumvent both the shortage of autologous chondrocytes and the regulatory barriers to cell-based therapies, we propose to regenerate cartilage and suppress hypertrophy and degeneration by injecting the novel NF-HMS microcarrier that delivers key biological molecules to activate endogenous bone marrow stromal cells (BMSCs) for hyaline cartilage regeneration and suppress. First, we will mechanistically determine whether HIF-1, HIF-2, or both promote chondrogenesis and prevent hypertrophy/degeneration. Second, we will develop TGF- and the HIF stabilizer releasing NF-HMS to facilitate the chondrogenic differentiation of human and rabbit BMSCs using in vitro and a subcutaneous implantation model. Third, we will use the novel injectable NF-HMS carrier to synergize TGF- and HIF activities of endogenous BMSCs in order to regenerate and maintain high-quality cartilage in a rabbit osteochondral repair model. By accomplishing these specific aims, we will substantially deepen our understanding of the key factors that affect chondrogenesis, cartilage regeneration, and prevention of hypertrophy and cartilage degeneration, leading to a novel cartilage repair therapy without using exogenous or exogenously manipulated cells. The understandings and strategies developed in this project can also be utilized to engineer other tissues. 1


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: 2024 ( Subtotal = $258,982 )
2024	2024	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT ST STE 440A	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	4	11/21/2023	NON-COMPETING CONTINUATION	$240,293
2024	2024	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT ST STE 440A	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	4	6/18/2024	NON-COMPETING CONTINUATION	$18,689
														Subtotal = $258,982

Issue Date FY: 2023 ( Subtotal = $0 )
2023	2022	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT ST STE 440A	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	3	1/18/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $264,275 )
2022	2022	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT ST STE 440A	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	002	3	9/20/2022	NON-COMPETING CONTINUATION	$0
2022	2022	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT ST STE 440A	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	3	1/19/2022	NON-COMPETING CONTINUATION	$240,249
2022	2022	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT ST STE 440A	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	3	5/11/2022	NON-COMPETING CONTINUATION	$24,026
														Subtotal = $264,275

Issue Date FY: 2021 ( Subtotal = -$60,884 )
2021	2020	REGENTS OF THE UNIVERSITY OF MICHIGAN	503 THOMPSON ST	ANN ARBOR	MI	48109	WASHTENAW	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	1	6/8/2021	NEW	-$343,200
2021	2020	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT ST STE 440A	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	2	6/9/2021	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$282,316
														Subtotal = -$60,884

Issue Date FY: 2020 ( Subtotal = $343,200 )
2020	2020	REGENTS OF THE UNIVERSITY OF MICHIGAN	503 THOMPSON ST	ANN ARBOR	MI	48109	WASHTENAW	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	1	9/23/2020	NEW	$343,200
														Subtotal = $343,200

Grand Total All Awards = $805,573

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Regenerating Hyaline Cartilage Using Nanofibrous Hollow Microspheres and Synergizing TGF-beta and HIF

Award Number: R01AR075770

ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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