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Tissue Engineering Strategies to Revitalize Allografts

Award Number: R01AR064200
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: 07/01/2023
PERIOD OF PERFORMANCE END DATE: 06/30/2027

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Tissue Engineering Strategies to Revitalize Allografts - There are limited options for reconstruction of bone defects resulting from congenital anomalies, trauma, infection, and oncologic resection. Over 2 million bone graft procedures are performed annually worldwide, with the clinical ‘gold standard’ being the use of autografts. Autografts fully heal and integrate, mediated by the periosteum, a thin layer of tissue and periosteal cells (PCs) surrounding bone. However, autografts are limited due to tissue availability and donor site morbidity. Thus, decellularized allografts are commonly employed. However, the limited ability of allografts, which lack periosteum, to remodel and integrate with the host tissue directly contributes to ~35% and 60% failure rates within 2 and 10 years of implantation. Periosteal-mediated healing is coordinated by a variety of contextual cues including matrix remodeling and adhesion and temporally defined release of paracrine factors. Our overarching hypothesis is that allograft healing will be dramatically improved by capturing critical healing cues in a tissue engineered periosteum (TEP). In the first funding cycle, we pioneered development of the TEP, which incorporates mesenchymal stem cells (MSCs) and OPs within hydrolytically degradable poly(ethylene glycol)(PEG)-based hydrogels, which are formed around allografts, similar to native periosteum. TEP shows outstanding promise to enhance murine allograft healing, resulting in a 300% increase in maximum fracture torque versus unmodified allografts at 9 weeks post-implantation. However, healing was plagued by fibrotic tissue, which results in the allograft limited to ~50% of autograft maximum torque. Fibrosis is consistent with poorly supported infiltration of TEP by host vessel/tissue, a limitation resulting from bulk hydrolytic TEP degradation which results in structural insufficiencies to support complete host-tissue infiltration. Thus, the focus of this renewal is a cellularly remodeled TEP, which enables localized, cell-demanded degradation while maintaining bulk hydrogel properties to support host-tissue infiltration. Three specific aims are outlined: Specific Aim 1: Tune TEP matrix cues (adhesive peptides and MMP-degradable crosslinks) to coordinate tissue infiltration and improve allograft healing. Specific Aim 2: Characterize TEP-mediated host-tissue recruitment. Specific Aim 3: Exploit the optimized TEP matrix to deliver peptides emulating periosteal paracrine cues as a translatable, acellular TEP. Successful completion of these Aims will significantly advance our understanding of how the periosteum coordinates allograft healing and the design of engineered periosteum to promote these bone regeneration processes. The developed material platforms and general approach are also readily applicable in other tissue engineering applications.


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: 2025 ( Subtotal = $420,027 )
2025	2025	UNIVERSITY OF OREGON	1776 E 13TH AVE	EUGENE	OR	97403	LANE	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	9	7/22/2025	NON-COMPETING CONTINUATION	$420,027
														Subtotal = $420,027

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2023	UNIVERSITY OF OREGON	1776 E 13TH AVE	EUGENE	OR	97403	LANE	USA	Arthritis, Musculoskeletal and Skin Diseases Research	004	8	5/8/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
2024	2023	UNIVERSITY OF OREGON	1776 E 13TH AVE	EUGENE	OR	97403	LANE	USA	Arthritis, Musculoskeletal and Skin Diseases Research	003	8	5/2/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$258,862
2024	2023	UNIVERSITY OF OREGON	1776 E 13TH AVE	EUGENE	OR	97403	LANE	USA	Arthritis, Musculoskeletal and Skin Diseases Research	005	8	6/7/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
2024	2022	UNIVERSITY OF ROCHESTER	910 GENESEE ST	ROCHESTER	NY	14611	MONROE	USA	Arthritis, Musculoskeletal and Skin Diseases Research	002	7	5/2/2024	SUPPLEMENT FOR EXPANSION	-$32,724
2024	2021	UNIVERSITY OF ROCHESTER	910 GENESEE ST	ROCHESTER	NY	14611	MONROE	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	7	5/2/2024	SUPPLEMENT FOR EXPANSION	-$19,661
2024	2021	UNIVERSITY OF ROCHESTER	910 GENESEE ST	ROCHESTER	NY	14611	MONROE	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	7	5/2/2024	NON-COMPETING CONTINUATION	-$206,477
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $422,350 )
2023	2023	UNIVERSITY OF OREGON	1585 E 13TH AVE	EUGENE	OR	97403	LANE	USA	Arthritis, Musculoskeletal and Skin Diseases Research	003	8	5/19/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$448,776
2023	2022	UNIVERSITY OF ROCHESTER	910 GENESEE ST	ROCHESTER	NY	14611	MONROE	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	7	3/23/2023	SUPPLEMENT FOR EXPANSION	-$26,426
2023	2021	UNIVERSITY OF ROCHESTER	910 GENESEE ST	ROCHESTER	NY	14611	MONROE	USA	Arthritis, Musculoskeletal and Skin Diseases Research	002	7	5/18/2023	NON-COMPETING CONTINUATION	$0
2023	2021	UNIVERSITY OF ROCHESTER	500 JOSEPH C WILSON BLVD	ROCHESTER	NY	14627	MONROE	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	7	1/19/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $422,350

Issue Date FY: 2022 ( Subtotal = $67,731 )
2022	2022	UNIVERSITY OF ROCHESTER	500 JOSEPH C WILSON BLVD	ROCHESTER	NY	14627	MONROE	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	7	8/5/2022	SUPPLEMENT FOR EXPANSION	$59,150
2022	2021	UNIVERSITY OF ROCHESTER	500 JOSEPH C WILSON BLVD	ROCHESTER	NY	14627	MONROE	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	7	8/4/2022	NON-COMPETING CONTINUATION	$0
2022	2017	UNIVERSITY OF ROCHESTER	500 JOSEPH C WILSON BLVD	ROCHESTER	NY	14627	MONROE	USA	Arthritis, Musculoskeletal and Skin Diseases Research	002	5	9/26/2022	NON-COMPETING CONTINUATION	$8,581
														Subtotal = $67,731

Issue Date FY: 2021 ( Subtotal = $566,951 )
2021	2021	UNIVERSITY OF ROCHESTER	500 JOSEPH C WILSON BLVD	ROCHESTER	NY	14627	MONROE	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	7	6/17/2021	NON-COMPETING CONTINUATION	$517,660
2021	2021	UNIVERSITY OF ROCHESTER	500 JOSEPH C WILSON BLVD	ROCHESTER	NY	14627	MONROE	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	7	9/9/2021	SUPPLEMENT FOR EXPANSION	$49,291
														Subtotal = $566,951

Issue Date FY: 2020 ( Subtotal = $460,643 )
2020	2020	UNIVERSITY OF ROCHESTER	500 JOSEPH C WILSON BLVD	ROCHESTER	NY	14627	MONROE	USA	Arthritis, Musculoskeletal and Skin Diseases Research	002	6	8/26/2020	COMPETING CONTINUATION	$522,668
2020	2017	UNIVERSITY OF ROCHESTER	500 JOSEPH C WILSON BLVD	ROCHESTER	NY	14627	MONROE	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	5	5/2/2020	NON-COMPETING CONTINUATION	-$8,358
2020	2017	UNIVERSITY OF ROCHESTER	500 JOSEPH C WILSON BLVD	ROCHESTER	NY	14627	MONROE	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	5	5/2/2020	SUPPLEMENT FOR EXPANSION	-$53,667
														Subtotal = $460,643

Issue Date FY: 2019 ( Subtotal = $0 )
2019	2017	UNIVERSITY OF ROCHESTER	500 JOSEPH C WILSON BLVD	ROCHESTER	NY	14627	MONROE	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	5	2/26/2019	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2017 ( Subtotal = $286,113 )
2017	2017	UNIVERSITY OF ROCHESTER	500 JOSEPH C WILSON BLVD	ROCHESTER	NY	14627	MONROE	USA	Arthritis, Musculoskeletal and Skin Diseases Research	003	5	6/14/2017	NON-COMPETING CONTINUATION	$29,358
2017	2017	UNIVERSITY OF ROCHESTER	601 ELMWOOD AVE	ROCHESTER	NY	14642	MONROE	USA	Arthritis, Musculoskeletal and Skin Diseases Research	002	5	3/23/2017	SUPPLEMENT FOR EXPANSION	$53,667
2017	2017	UNIVERSITY OF ROCHESTER	601 ELMWOOD AVE	ROCHESTER	NY	14642	MONROE	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	5	2/23/2017	NON-COMPETING CONTINUATION	$311,321
2017	2017	UNIVERSITY OF ROCHESTER	601 ELMWOOD AVE	ROCHESTER	NY	14642	MONROE	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	5	2/28/2017	NON-COMPETING CONTINUATION	-$108,233
														Subtotal = $286,113

Issue Date FY: 2016 ( Subtotal = $345,913 )
2016	2016	UNIVERSITY OF ROCHESTER	1325 MOUNT HOPE AVE, SUITE 260	ROCHESTER	NY	14642	MONROE	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	4	3/2/2016	EXTENSION WITH OR WITHOUT FUNDS	$345,913
														Subtotal = $345,913

Issue Date FY: 2015 ( Subtotal = $338,213 )
2015	2015	UNIVERSITY OF ROCHESTER	1325 MOUNT HOPE AVE, SUITE 260	ROCHESTER	NY	14642	MONROE	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	3	5/6/2015	SUPPLEMENT FOR EXPANSION	$44,644
2015	2015	UNIVERSITY OF ROCHESTER	1325 MOUNT HOPE AVE, SUITE 260	ROCHESTER	NY	14642	MONROE	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	3	2/26/2015	NON-COMPETING CONTINUATION	$293,569
														Subtotal = $338,213

Issue Date FY: 2014 ( Subtotal = $326,188 )
2014	2014	UNIVERSITY OF ROCHESTER	1325 MOUNT HOPE AVE, SUITE 260	ROCHESTER	NY	14642	MONROE	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	2	3/14/2014	NON-COMPETING CONTINUATION	$326,188
														Subtotal = $326,188

Issue Date FY: 2013 ( Subtotal = $293,569 )
2013	2013	UNIVERSITY OF ROCHESTER	1325 MOUNT HOPE AVE, SUITE 260	ROCHESTER	NY	14642	MONROE	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	1	3/1/2013	NEW	$293,569
														Subtotal = $293,569

Grand Total All Awards = $3,527,698

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Tissue Engineering Strategies to Revitalize Allografts

Award Number: R01AR064200

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: 07/01/2023

PERIOD OF PERFORMANCE END DATE: 06/30/2027

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