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Engineering a biopolymer hydrogel to inhibit osteogenesis: Implications for growth plate repair

Award Number: R21AR071585
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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Project Summary Every year, a substantial number of children injure a growth plate, a cartilaginous region found at the end of all long bones in children that provides signals for the bones to lengthen. The growth plate is the most fragile structure in a child’s developing bones, making it prone to injury. Damaged cartilage within the growth plate is often replaced by unwanted bone, forming a “bony bar”, which can lead to angular deformities or halt bone growth completely. Current surgical methods to correct bone growth defects are invasive, prone to infections and have low success rates. There is no current treatment that leads to complete repair of an injured growth plate. Innovative treatment strategies that prevent bony bar formation, restore functional growth plate cartilage, and permit normal longitudinal bone growth in affected individuals are greatly needed. This proposal seeks to develop an injectable hydrogel biomaterial system that could prevent bony bar formation and promote the formation of cartilage tissue, and which could ultimately be examined for its ability to heal growth plate injuries in children. It has been shown that mesenchymal stem cells (MSCs) infiltrate the injured growth plate and undergo osteogenic differentiation. Here, two important areas for inhibiting the osteogenesis of MSCs via a biomaterial system will be studied: (1) the role of biopolymer hydrogel substrate mechanics in preventing osteogenesis, and (2) the delivery of short interfering RNA (siRNA) from biopolymer hydrogels that can block osteogenic differentiation. We hypothesize that hydrogel systems that are less stiff and that provide sustained exposure of MSCs to p38 MAPK siRNA will inhibit osteogenesis. This proposal seeks to engineer hydrogel systems with these characteristics as a first step towards creating new technologies for helping to heal growth plate injuries in children. This will be accomplished as by two Aims: Aim 1 - To engineer a hydrogel system with mechanical cues that prevent osteogenic differentiation of MSCs. Aim 2 - To design a hydrogel that would provide sustained release of siRNA targeting p38 MAPK to prevent osteogenesis of MSCs. The p38 MAPK pathway has been linked to osteogenesis in various cell types, including MSCs. Local inhibition of this pathway by siRNA could prevent MSC osteogenesis from occurring after growth plate injury. For both Aims, these studies will be conducted in vitro and also in vivo in a rat growth plate injury model. This project is a first step towards successful development of a biomaterial system that can prevent MSC osteogenesis, which could ultimately aid in growth plate tissue 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: 2024 ( Subtotal = $0 )
2024	2019	TRUSTEES OF THE COLORADO SCHOOL OF MINES	1500 ILLINOIS ST	GOLDEN	CO	80401	JEFFERSON	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	2	12/19/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $0 )
2022	2019	TRUSTEES OF THE COLORADO SCHOOL OF MINES	1500 ILLINOIS ST	GOLDEN	CO	80401	JEFFERSON	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	2	3/14/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $0 )
2021	2019	TRUSTEES OF THE COLORADO SCHOOL OF MINES	1500 ILLINOIS ST	GOLDEN	CO	80401	JEFFERSON	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	2	2/4/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2019 ( Subtotal = $188,190 )
2019	2019	TRUSTEES OF THE COLORADO SCHOOL OF MINES	1500 ILLINOIS ST	GOLDEN	CO	80401	JEFFERSON	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	2	3/6/2019	NON-COMPETING CONTINUATION	$188,190
														Subtotal = $188,190

Issue Date FY: 2018 ( Subtotal = $165,527 )
2018	2018	TRUSTEES OF THE COLORADO SCHOOL OF MINES	1500 ILLINOIS ST	GOLDEN	CO	80401	JEFFERSON	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	1	5/5/2018	NEW	$165,527
														Subtotal = $165,527

Grand Total All Awards = $353,717

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Engineering a biopolymer hydrogel to inhibit osteogenesis: Implications for growth plate repair

Award Number: R21AR071585

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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