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3D printed muscle-bone organ implant for treating large injuries

Award Number: R01AR073135
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: 11/19/2020
PERIOD OF PERFORMANCE END DATE: 03/31/2024

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3D printed muscle-bone organ implant for treating large injuries - PROJECT SUMMARY In the United States, musculoskeletal diseases such as extremity injuries, burns, and tumors are a leading cause of disabilities and death, affecting one in two individuals. However, until now, there has been no effective implant that can replace the structure and function of damaged bone and muscle tissues, likely due to the difficulty of regulating the sophisticated heterogeneous bone-muscle junction structure. As a result, muscle damage has been largely ignored during musculoskeletal surgeries, which often results in disconnected tissues and fibrous tissue formation, leading to temporal or permanent musculoskeletal disability. In fact, in the human musculoskeletal system, there exists a direct attachment between bone and muscle tissues at a wide area of bone, forming a “bone-muscle unit.” Based on this structural closeness, the growth and development of bone and muscle are tightly coupled through growth factor signaling and cellular cross-talk. Therefore, damage to either bone or muscle can deteriorate health and function of the other tissue type. For this reason, there has been a strong need for developing an innovative musculoskeletal implant, which can integrate the distinguished physicochemical properties of hard tissue and soft tissue in a spatially controlled manner. To address this problem, we aim to design and build the first 3D printed muscle-bone implant, by utilizing state- of-the-art 3D multimaterial bioprinting that can extrude multiple types of tissue mimetic bioinks in a simultaneous and continuous manner. We will control the physicochemical properties of bioinks, such as viscosity and porosity, to provide an optimized artificial niche for the growth and differentiation of each cell type. We will also include biodegradable drug carriers to supply musculogenic and osteogenic growth factors with controlled release kinetic behavior, to aid tissue recovery. In addition, we will regulate the parameters for bioprinting, such as pneumatic pressure, and the injection and photocrosslinking conditions to build a 3D structure. We will then mature the 3D printed muscle-bone organ implant in a customized bioreactor system by applying compression and relaxation cycles that mimic musculoskeletal movement in vivo. Finally, we will evaluate the musculoskeletal regeneration capacity of our 3D printed muscle-bone implant in a mouse volumetric muscle loss and bone defect model. This research will present the first 3D print muscle-bone tissues with continuous structures ex vivo that can provide a groundbreaking clinical solution for curing severe musculoskeletal injuries and preventing disabilities in the clinic. We further expect that our 3D printed muscle-bone tissue platform will be beneficial for understanding developmental principles and pathological mechanisms of the musculoskeletal system.


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 = $0 )
2024	2022	TERASAKI INSTITUTE FOR BIOMEDICAL INNOVATION	21100 ERWIN ST	WOODLAND HILLS	CA	91367	LOS ANGELES	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	6	8/5/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $417,860 )
2022	2022	TERASAKI INSTITUTE FOR BIOMEDICAL INNOVATION	1018 WESTWOOD BLVD	LOS ANGELES	CA	90024	LOS ANGELES	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	6	8/5/2022	NON-COMPETING CONTINUATION	$37,990
2022	2022	TERASAKI INSTITUTE FOR BIOMEDICAL INNOVATION	1018 WESTWOOD BLVD	LOS ANGELES	CA	90024	LOS ANGELES	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	6	3/22/2022	NON-COMPETING CONTINUATION	$379,870
														Subtotal = $417,860

Issue Date FY: 2021 ( Subtotal = $417,874 )
2021	2021	TERASAKI INSTITUTE FOR BIOMEDICAL INNOVATION	1018 WESTWOOD BLVD	LOS ANGELES	CA	90024	LOS ANGELES	USA	Arthritis, Musculoskeletal and Skin Diseases Research	003	5	4/14/2021	NON-COMPETING CONTINUATION	$414,418
2021	2020	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Arthritis, Musculoskeletal and Skin Diseases Research	002	3	2/4/2021	NON-COMPETING CONTINUATION	$0
2021	2020	TERASAKI INSTITUTE FOR BIOMEDICAL INNOVATION	1018 WESTWOOD BLVD	LOS ANGELES	CA	90024	LOS ANGELES	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	4	11/19/2020	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$432,174
2021	2020	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90095	LOS ANGELES	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	3	11/18/2020	NON-COMPETING CONTINUATION	-$428,718
														Subtotal = $417,874

Issue Date FY: 2020 ( Subtotal = $428,718 )
2020	2020	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90095	LOS ANGELES	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	3	5/25/2020	NON-COMPETING CONTINUATION	$428,718
														Subtotal = $428,718

Issue Date FY: 2019 ( Subtotal = $433,024 )
2019	2019	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90095	LOS ANGELES	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	2	3/28/2019	NON-COMPETING CONTINUATION	$433,024
														Subtotal = $433,024

Issue Date FY: 2018 ( Subtotal = $453,761 )
2018	2018	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90095	LOS ANGELES	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	1	4/26/2018	NEW	$453,761
														Subtotal = $453,761

Grand Total All Awards = $2,151,237

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3D printed muscle-bone organ implant for treating large injuries

Award Number: R01AR073135

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: 11/19/2020

PERIOD OF PERFORMANCE END DATE: 03/31/2024

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