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Suturable bioprinted vascularized muscle constructs for treatment of skeletal muscle loss

Award Number: R01AR077132
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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Suturable bioprinted vascularized muscle constructs for treatment of skeletal muscle loss - Project Summary Volumetric muscle loss (VML) usually occurs following traumatic injury and results in a composite loss of muscle mass. These injuries manifest in decreased strength and functional impairments. Clinically, these injuries often heal with fibrosis, as opposed to skeletal muscle regeneration. Current existing therapeutic options are also insufficient for VML treatment, and complications are often associated with surgical repair including nerve injury, excessive immune response, infection, scarring, and limitations of tissue graft supply. Indeed, natural healing and surgical procedures are inefficient in restoring the functionality of injured muscles, resulting in a poor quality of life. Therefore, developing clinically relevant three-dimensional (3D) tissue using patient-specific genetically identical cells has emerged as a potential solution to address the above issues. To achieve this aim, there are two existing main challenges. The first challenge is obtaining large amounts of patient-specific genetically identical cells. The use of human pluripotent stem cells (hiPSCs) differentiated to the muscle lineage represents a promising candidate to build upon personalized therapy. However, directing the differentiation of hiPSCs to the muscle fate along with reproducible differentiation schemes has proven to be challenging. The second challenge is developing a highly organized and vascularized 3D skeletal muscle tissue to maintain the viability of cells inside thick tissue constructs via engineered vessel networks. Furthermore, the fabricated tissues have to strongly integrate into injured site via surgical methods. To address these challenges, we plan to develop a suturable 3D vascularized muscle tissue from hiPSC-derived myogenic precursor cells (hiPSC-MPCs) embedded in biomaterials using bioprinting techniques. We will optimize the recently developed protocols allowing efficient production of functional myofibers from hiPSCs in hydrogels with tunable mechanical properties and degradable profiles, which mimic the extracellular matrix (ECM) of native skeletal muscle tissue. To create biomimetic vascularized muscle constructs, a multi-material embedded bioprinting technique will be used to precisely control the positions of the vascular network and aligned muscle fibers with biologically relevant architectures. With the conventional bioprinting system, it is difficult to precisely control the materials’ position in Z directions to create freestanding hydrogel architectures. Also, to achieve prolonged retention of implants into the injured site and to improve muscle regeneration, a muscle growth factor (IGF-1) laden suturable graft will be developed. hiPSC-MPCs-laden constructs will be printed on the suturable graft consisting of IGF-1-laden PGS/GelMA substrates using electrospinning.


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 = $453,645 )
2025	2025	BRIGHAM & WOMENS HOSPITAL INC	75 FRANCIS ST	BOSTON	MA	02115	SUFFOLK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	5	2/14/2025	NON-COMPETING CONTINUATION	$453,645
														Subtotal = $453,645

Issue Date FY: 2024 ( Subtotal = $492,741 )
2024	2024	BRIGHAM & WOMENS HOSPITAL INC	75 FRANCIS ST	BOSTON	MA	02115	SUFFOLK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	4	1/23/2024	NON-COMPETING CONTINUATION	$457,182
2024	2024	BRIGHAM & WOMENS HOSPITAL INC	75 FRANCIS ST	BOSTON	MA	02115	SUFFOLK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	4	6/12/2024	NON-COMPETING CONTINUATION	$35,559
														Subtotal = $492,741

Issue Date FY: 2023 ( Subtotal = $531,030 )
2023	2023	BRIGHAM & WOMENS HOSPITAL INC	75 FRANCIS ST	BOSTON	MA	02115	SUFFOLK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	3	4/24/2023	NON-COMPETING CONTINUATION	$53,103
2023	2023	BRIGHAM & WOMENS HOSPITAL INC	75 FRANCIS ST	BOSTON	MA	02115	SUFFOLK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	3	1/19/2023	NON-COMPETING CONTINUATION	$477,927
														Subtotal = $531,030

Issue Date FY: 2022 ( Subtotal = $536,504 )
2022	2022	BRIGHAM AND WOMEN'S HOSPITAL, INC., THE	75 FRANCIS ST	BOSTON	MA	02115	SUFFOLK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	2	2/17/2022	NON-COMPETING CONTINUATION	$487,730
2022	2022	BRIGHAM AND WOMEN'S HOSPITAL, INC., THE	75 FRANCIS ST	BOSTON	MA	02115	SUFFOLK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	2	5/30/2022	NON-COMPETING CONTINUATION	$48,774
														Subtotal = $536,504

Issue Date FY: 2021 ( Subtotal = $542,120 )
2021	2021	BRIGHAM AND WOMEN'S HOSPITAL, INC., THE	75 FRANCIS ST	BOSTON	MA	02115	SUFFOLK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	1	2/16/2021	NEW	$542,120
														Subtotal = $542,120

Grand Total All Awards = $2,556,040

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Suturable bioprinted vascularized muscle constructs for treatment of skeletal muscle loss

Award Number: R01AR077132

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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