Bioactive extracellular matrix scaffolds engineered with proangiogenic proteoglycan mimetics and loaded with endothelial progenitor cells promote neovascularization and diabetic wound healing

Diabetic ischemic wound treatment remains a critical clinical challenge. Neovascularization plays a significant role in wound healing during all stages of the tissue repair process. Strategies that enhance angiogenesis and neovascularization and improve ischemic pathology may promote the healing of...

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Autores principales:	Siqi He, Tanaya Walimbe, Hongyuan Chen, Kewa Gao, Priyadarsini Kumar, Yifan Wei, Dake Hao, Ruiwu Liu, Diana L. Farmer, Kit S. Lam, Jianda Zhou, Alyssa Panitch, Aijun Wang
Formato:	article
Lenguaje:	EN
Publicado:	KeAi Communications Co., Ltd. 2022
Materias:	Diabetic ischemic wound ECM scaffold Endothelial progenitor cells Neovascularization Wound healing Materials of engineering and construction. Mechanics of materials TA401-492 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/e0cf9bdd9cf540b48f856c8d765dacfb
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spelling	oai:doaj.org-article:e0cf9bdd9cf540b48f856c8d765dacfb2021-11-28T04:35:11ZBioactive extracellular matrix scaffolds engineered with proangiogenic proteoglycan mimetics and loaded with endothelial progenitor cells promote neovascularization and diabetic wound healing2452-199X10.1016/j.bioactmat.2021.08.017https://doaj.org/article/e0cf9bdd9cf540b48f856c8d765dacfb2022-04-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2452199X21003935https://doaj.org/toc/2452-199XDiabetic ischemic wound treatment remains a critical clinical challenge. Neovascularization plays a significant role in wound healing during all stages of the tissue repair process. Strategies that enhance angiogenesis and neovascularization and improve ischemic pathology may promote the healing of poor wounds, particularly diabetic wounds in highly ischemic conditions. We previously identified a cyclic peptide LXW7 that specifically binds to integrin αvβ3 on endothelial progenitor cells (EPCs) and endothelial cells (ECs), activates vascular endothelial growth factor (VEGF) receptors, and promotes EC growth and maturation. In this study, we designed and synthesized a multi-functional pro-angiogenic molecule by grafting LXW7 and collagen-binding peptides (SILY) to a dermatan sulfate (DS) glycosaminoglycan backbone, named LXW7-DS-SILY, and further employed this multi-functional molecule to functionalize collagen-based extracellular matrix (ECM) scaffolds. We confirmed that LXW7-DS-SILY modification significantly promoted EPC attachment and growth on the ECM scaffolds in vitro and supported EPC survival in vivo in the ischemic environment. When applied in an established Zucker Diabetic Fatty (ZDF) rat ischemic skin flap model, LXW7-DS-SILY-functionalized ECM scaffolds loaded with EPCs significantly improved wound healing, enhanced neovascularization and modulated collagen fibrillogenesis in the ischemic environment. Altogether, this study provides a promising novel treatment to accelerate diabetic ischemic wound healing, thereby reducing limb amputation and mortality of diabetic patients.Siqi HeTanaya WalimbeHongyuan ChenKewa GaoPriyadarsini KumarYifan WeiDake HaoRuiwu LiuDiana L. FarmerKit S. LamJianda ZhouAlyssa PanitchAijun WangKeAi Communications Co., Ltd.articleDiabetic ischemic woundECM scaffoldEndothelial progenitor cellsNeovascularizationWound healingMaterials of engineering and construction. Mechanics of materialsTA401-492Biology (General)QH301-705.5ENBioactive Materials, Vol 10, Iss , Pp 460-473 (2022)
institution	DOAJ
collection	DOAJ
language	EN
topic	Diabetic ischemic wound ECM scaffold Endothelial progenitor cells Neovascularization Wound healing Materials of engineering and construction. Mechanics of materials TA401-492 Biology (General) QH301-705.5
spellingShingle	Diabetic ischemic wound ECM scaffold Endothelial progenitor cells Neovascularization Wound healing Materials of engineering and construction. Mechanics of materials TA401-492 Biology (General) QH301-705.5 Siqi He Tanaya Walimbe Hongyuan Chen Kewa Gao Priyadarsini Kumar Yifan Wei Dake Hao Ruiwu Liu Diana L. Farmer Kit S. Lam Jianda Zhou Alyssa Panitch Aijun Wang Bioactive extracellular matrix scaffolds engineered with proangiogenic proteoglycan mimetics and loaded with endothelial progenitor cells promote neovascularization and diabetic wound healing
description	Diabetic ischemic wound treatment remains a critical clinical challenge. Neovascularization plays a significant role in wound healing during all stages of the tissue repair process. Strategies that enhance angiogenesis and neovascularization and improve ischemic pathology may promote the healing of poor wounds, particularly diabetic wounds in highly ischemic conditions. We previously identified a cyclic peptide LXW7 that specifically binds to integrin αvβ3 on endothelial progenitor cells (EPCs) and endothelial cells (ECs), activates vascular endothelial growth factor (VEGF) receptors, and promotes EC growth and maturation. In this study, we designed and synthesized a multi-functional pro-angiogenic molecule by grafting LXW7 and collagen-binding peptides (SILY) to a dermatan sulfate (DS) glycosaminoglycan backbone, named LXW7-DS-SILY, and further employed this multi-functional molecule to functionalize collagen-based extracellular matrix (ECM) scaffolds. We confirmed that LXW7-DS-SILY modification significantly promoted EPC attachment and growth on the ECM scaffolds in vitro and supported EPC survival in vivo in the ischemic environment. When applied in an established Zucker Diabetic Fatty (ZDF) rat ischemic skin flap model, LXW7-DS-SILY-functionalized ECM scaffolds loaded with EPCs significantly improved wound healing, enhanced neovascularization and modulated collagen fibrillogenesis in the ischemic environment. Altogether, this study provides a promising novel treatment to accelerate diabetic ischemic wound healing, thereby reducing limb amputation and mortality of diabetic patients.
format	article
author	Siqi He Tanaya Walimbe Hongyuan Chen Kewa Gao Priyadarsini Kumar Yifan Wei Dake Hao Ruiwu Liu Diana L. Farmer Kit S. Lam Jianda Zhou Alyssa Panitch Aijun Wang
author_facet	Siqi He Tanaya Walimbe Hongyuan Chen Kewa Gao Priyadarsini Kumar Yifan Wei Dake Hao Ruiwu Liu Diana L. Farmer Kit S. Lam Jianda Zhou Alyssa Panitch Aijun Wang
author_sort	Siqi He
title	Bioactive extracellular matrix scaffolds engineered with proangiogenic proteoglycan mimetics and loaded with endothelial progenitor cells promote neovascularization and diabetic wound healing
title_short	Bioactive extracellular matrix scaffolds engineered with proangiogenic proteoglycan mimetics and loaded with endothelial progenitor cells promote neovascularization and diabetic wound healing
title_full	Bioactive extracellular matrix scaffolds engineered with proangiogenic proteoglycan mimetics and loaded with endothelial progenitor cells promote neovascularization and diabetic wound healing
title_fullStr	Bioactive extracellular matrix scaffolds engineered with proangiogenic proteoglycan mimetics and loaded with endothelial progenitor cells promote neovascularization and diabetic wound healing
title_full_unstemmed	Bioactive extracellular matrix scaffolds engineered with proangiogenic proteoglycan mimetics and loaded with endothelial progenitor cells promote neovascularization and diabetic wound healing
title_sort	bioactive extracellular matrix scaffolds engineered with proangiogenic proteoglycan mimetics and loaded with endothelial progenitor cells promote neovascularization and diabetic wound healing
publisher	KeAi Communications Co., Ltd.
publishDate	2022
url	https://doaj.org/article/e0cf9bdd9cf540b48f856c8d765dacfb
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Bioactive extracellular matrix scaffolds engineered with proangiogenic proteoglycan mimetics and loaded with endothelial progenitor cells promote neovascularization and diabetic wound healing

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