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Acellular composite hydrogel scaffolds for volumetric muscle regeneration

Award Number: R21AR079708
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: 02/01/2022
PERIOD OF PERFORMANCE END DATE: 01/31/2026

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Acellular composite hydrogel scaffolds for volumetric muscle regeneration - Project Summary There are almost 5 million reconstructive procedures performed annually as a result of traumatic injury, cancer ablation, cosmetic procedures, or combat injuries. The destruction or removal of large amounts of skeletal muscle, termed volumetric muscle loss (VML), resulting from traumatic events such as car crashes or combat injuries, represents a significant health concern. Skeletal muscle is highly vascularized, and relies on adequate infiltration of blood vessels to repair and regenerate. The gold standard for VML repair is autologous grafting, and is limited by reduced functional outcomes and inadequate host-mediated graft revascularization. Current biomaterial-based tissue engineered approaches towards the repair of skeletal muscle tissue after VML rely on passive neovascularization from the host, as opposed to actively recruiting vascular networks to accompany satellite cell infiltration during repair. As such, there remains a significant need to develop materials that will actively stimulate the development of vasculature that will guide organized and aligned skeletal muscle tissue regeneration. We hypothesize that scaffolds that stimulate the rapid creation of a new vasculature and aligned muscle tissue will significantly enhance skeletal muscle repair in VML injuries. To test this hypothesis, we will create a class of biodegradable composite scaffolds that will be implanted into VML injuries to enable the recruitment of endothelial cells and satellite cells. As such, the objective is to create a composite material that promotes in situ regeneration of mature functional muscle tissue. To fabricate these scaffolds, collagen sponges with defined, anisotropic architectures will be fabricated and embedded with angiogenic self-assembling peptide hydrogels, termed SLan (Aim 1). Assessment of the mechanics of scaffolds will complement in vitro analyses of cellular infiltration and compatibility to define material parameters that will induce aligned vascularized skeletal muscle tissue. Scaffolds comprised of collagen, SLan, or composites will then be implanted into a murine model of VML to assess the contribution of each material to enhance VML repair (Aim 2). Particular emphasis will be placed on the ability of these scaffolds to support functional recovery as measured by muscular contraction in longitudinal studies. Histologic assessments will characterize i) the cellular infiltrate and the contribution of aligned scaffolds to guide organized skeletal muscle tissue growth, ii) the modulation of in situ neovascularization and supporting structures, and iii) changes in inflammation. Ultimately, we aim to address two major limitations within skeletal muscle tissue regeneration: i) inadequate vascularization of constructs in situ, and ii) the lack of organized alignment of nascent myofibers during repair of VML injuries; both factors known to inhibit functional recovery. These outcomes will result in the creation of a new class of composite materials to functionally drive cellular infiltration with hydrogels that are specifically designed to recruit specific supporting structures necessary for tissue regeneration and repair.


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 = $0 )
2025	2023	NEW JERSEY INSTITUTE OF TECHNOLOGY	323 DR MARTIN LUTHER KING JR BLVD	NEWARK	NJ	07102	ESSEX	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	2	12/24/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $301,474 )
2023	2023	NEW JERSEY INSTITUTE OF TECHNOLOGY	323 DR MARTIN LUTHER KING JR BLVD	NEWARK	NJ	07102	ESSEX	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	2	1/12/2023	NON-COMPETING CONTINUATION	$179,306
2023	2023	NEW JERSEY INSTITUTE OF TECHNOLOGY	323 DR MARTIN LUTHER KING JR BLVD	NEWARK	NJ	07102	ESSEX	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	2	2/27/2023	NON-COMPETING CONTINUATION	$19,923
2023	2023	NEW JERSEY INSTITUTE OF TECHNOLOGY	323 DR MARTIN LUTHER KING JR BLVD	NEWARK	NJ	07102	ESSEX	USA	Arthritis, Musculoskeletal and Skin Diseases Research	002	2	7/12/2023	SUPPLEMENT FOR EXPANSION	$102,245
														Subtotal = $301,474

Issue Date FY: 2022 ( Subtotal = $165,681 )
2022	2022	NEW JERSEY INSTITUTE OF TECHNOLOGY	323 DR MARTIN LUTHER KING JR BLVD	NEWARK	NJ	07102	ESSEX	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	1	1/25/2022	NEW	$165,681
														Subtotal = $165,681

Grand Total All Awards = $467,155

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Acellular composite hydrogel scaffolds for volumetric muscle regeneration

Award Number: R21AR079708

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: 02/01/2022

PERIOD OF PERFORMANCE END DATE: 01/31/2026

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