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Muscle-driven, implanted endoprostheses for musculoskeletal limb reconstruction

Award Number: R33AR078096
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: 09/11/2020
PERIOD OF PERFORMANCE END DATE: 01/31/2025

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Muscle-driven, implanted endoprostheses for musculoskeletal limb reconstruction - PROJECT SUMMARY The long-term goal of the proposed translational project is to improve the sensorimotor function of people with amputation and other severe musculoskeletal defects. Physically attaching muscles to limb prostheses could restore natural motor and sensory function to patients. Since all prostheses must be worn externally on the body, the previous approach required transferring muscle forces through skin, which had limitations in function and appearance. To better facilitate physical muscle-prosthesis attachment, the proposed project introduces endoprostheses, which are jointed limb prostheses that can be completely implanted within living skin. The geometry and mechanical properties will likely differ between endoprosthetic and biological limbs, and endoprostheses may be implanted at different times across clinical cases. There is an urgent need to understand how the endoprosthesis and muscle reattachment timing affect muscle structure and motor function. The overall objective of the proposed project is to determine the effects and interactions of muscle reattachment timing (immediate vs delayed) and context (biological vs endoprosthetic limb) on muscle structure and motor function in a rabbit model of below-knee amputation. The project’s central hypothesis is that muscle structure and motor function will recover with delayed reattachment across an endoprosthetic ankle but will be best when reattached immediately across a biological ankle. The rationale for the proposed research is that it will provide critical in vivo data to support our future research and inform how endoprostheses are implemented clinically. Phase 1 of the project includes two aims: (Aim 1) quantify the effect of reattachment timing on muscle structure and motor function in a biological limb context, and (Aim 2) determine the effect of muscle reattachment context (biological vs endoprosthetic limb) on muscle structure and motor function. In Phase 2, Aim 3 is to evaluate the interaction effect of reattachment timing and context. The endoprosthesis will replace the rabbit hindlimb ankle and foot, and muscles in the residual limb will be attached across the endoprosthetic ankle using synthetic tendon. Muscle structure will be measured by ultrasound imaging, tissue measurements, and histology. Motor function will be assessed by measuring hindlimb biomechanics during locomotion and ankle force-generating capacity during electrical stimulation of muscles attached to the endoprosthesis. The expected outcomes of the proposed research are a working in vivo experimental platform – an MDE prototype and animal model – data on muscle structure and motor function for different reattachment timings and contexts. The endoprostheses concept is highly innovative and radically different from existing externally worn limb prostheses. Endoprostheses are significant because they will enhance sensorimotor function and make limb prostheses more attractive, comfortable, and convenient to use, drastically improving patients’ independence and quality of life.


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 = -$4,276 )
2025	2023	UNIVERSITY OF TENNESSEE	201 ANDY HOLT TOWER	KNOXVILLE	TN	37996	KNOX	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	3	6/17/2025	EXTENSION WITH OR WITHOUT FUNDS	-$4,276
														Subtotal = -$4,276

Issue Date FY: 2024 ( Subtotal = $17,437 )
2024	2023	UNIVERSITY OF TENNESSEE	201 ANDY HOLT TOWER	KNOXVILLE	TN	37996	KNOX	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	3	2/8/2024	EXTENSION WITH OR WITHOUT FUNDS	$17,437
2024	2023	UNIVERSITY OF TENNESSEE	201 ANDY HOLT TOWER	KNOXVILLE	TN	37996	KNOX	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	3	5/14/2024	EXTENSION WITH OR WITHOUT FUNDS	$0
														Subtotal = $17,437

Issue Date FY: 2023 ( Subtotal = $331,701 )
2023	2023	UNIVERSITY OF TENNESSEE	201 ANDY HOLT TOWER	KNOXVILLE	TN	37996	KNOX	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	3	5/11/2023	EXTENSION WITH OR WITHOUT FUNDS	$331,701
														Subtotal = $331,701

Grand Total All Awards = $344,863

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Muscle-driven, implanted endoprostheses for musculoskeletal limb reconstruction

Award Number: R33AR078096

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: 09/11/2020

PERIOD OF PERFORMANCE END DATE: 01/31/2025

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