Post-Stroke Timing of ECM Hydrogel Implantation Affects Biodegradation and Tissue Restoration

Extracellular matrix (ECM) hydrogel promotes tissue regeneration in lesion cavities after stroke. However, a bioscaffold’s regenerative potential needs to be considered in the context of the evolving pathological environment caused by a stroke. To evaluate this key issue in rats, ECM hydrogel was de...

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Autores principales:	Corina Damian, Harmanvir Ghuman, Carrinton Mauney, Reem Azar, Janina Reinartz, Stephen F. Badylak, Michel Modo
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	extracellular matrix hydrogel therapeutic window stroke regeneration tissue repair Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/282fbb61b7db4d85a399dbcef1b8e54b
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spelling	oai:doaj.org-article:282fbb61b7db4d85a399dbcef1b8e54b2021-11-11T16:50:34ZPost-Stroke Timing of ECM Hydrogel Implantation Affects Biodegradation and Tissue Restoration10.3390/ijms2221113721422-00671661-6596https://doaj.org/article/282fbb61b7db4d85a399dbcef1b8e54b2021-10-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11372https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Extracellular matrix (ECM) hydrogel promotes tissue regeneration in lesion cavities after stroke. However, a bioscaffold’s regenerative potential needs to be considered in the context of the evolving pathological environment caused by a stroke. To evaluate this key issue in rats, ECM hydrogel was delivered to the lesion core/cavity at 7-, 14-, 28-, and 90-days post-stroke. Due to a lack of tissue cavitation 7-days post-stroke, implantation of ECM hydrogel did not achieve a sufficient volume and distribution to warrant comparison with the other time points. Biodegradation of ECM hydrogel implanted 14- and 28-days post-stroke were efficiently (80%) degraded by 14-days post-bioscaffold implantation, whereas implantation 90-days post-stroke revealed only a 60% decrease. Macrophage invasion was robust at 14- and 28-days post-stroke but reduced in the 90-days post-stroke condition. The pro-inflammation (M1) and pro-repair (M2) phenotype ratios were equivalent at all time points, suggesting that the pathological environment determines macrophage invasion, whereas ECM hydrogel defines their polarization. Neural cells (neural progenitors, neurons, astrocytes, oligodendrocytes) were found at all time points, but a 90-days post-stroke implantation resulted in reduced densities of mature phenotypes. Brain tissue restoration is therefore dependent on an efficient delivery of a bioscaffold to a tissue cavity, with 28-days post-stroke producing the most efficient biodegradation and tissue regeneration, whereas by 90-days post-stroke, these effects are significantly reduced. Improving our understanding of how the pathological environment influences biodegradation and the tissue restoration process is hence essential to devise engineering strategies that could extend the therapeutic window for bioscaffolds to repair the damaged brain.Corina DamianHarmanvir GhumanCarrinton MauneyReem AzarJanina ReinartzStephen F. BadylakMichel ModoMDPI AGarticleextracellular matrixhydrogeltherapeutic windowstrokeregenerationtissue repairBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11372, p 11372 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	extracellular matrix hydrogel therapeutic window stroke regeneration tissue repair Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	extracellular matrix hydrogel therapeutic window stroke regeneration tissue repair Biology (General) QH301-705.5 Chemistry QD1-999 Corina Damian Harmanvir Ghuman Carrinton Mauney Reem Azar Janina Reinartz Stephen F. Badylak Michel Modo Post-Stroke Timing of ECM Hydrogel Implantation Affects Biodegradation and Tissue Restoration
description	Extracellular matrix (ECM) hydrogel promotes tissue regeneration in lesion cavities after stroke. However, a bioscaffold’s regenerative potential needs to be considered in the context of the evolving pathological environment caused by a stroke. To evaluate this key issue in rats, ECM hydrogel was delivered to the lesion core/cavity at 7-, 14-, 28-, and 90-days post-stroke. Due to a lack of tissue cavitation 7-days post-stroke, implantation of ECM hydrogel did not achieve a sufficient volume and distribution to warrant comparison with the other time points. Biodegradation of ECM hydrogel implanted 14- and 28-days post-stroke were efficiently (80%) degraded by 14-days post-bioscaffold implantation, whereas implantation 90-days post-stroke revealed only a 60% decrease. Macrophage invasion was robust at 14- and 28-days post-stroke but reduced in the 90-days post-stroke condition. The pro-inflammation (M1) and pro-repair (M2) phenotype ratios were equivalent at all time points, suggesting that the pathological environment determines macrophage invasion, whereas ECM hydrogel defines their polarization. Neural cells (neural progenitors, neurons, astrocytes, oligodendrocytes) were found at all time points, but a 90-days post-stroke implantation resulted in reduced densities of mature phenotypes. Brain tissue restoration is therefore dependent on an efficient delivery of a bioscaffold to a tissue cavity, with 28-days post-stroke producing the most efficient biodegradation and tissue regeneration, whereas by 90-days post-stroke, these effects are significantly reduced. Improving our understanding of how the pathological environment influences biodegradation and the tissue restoration process is hence essential to devise engineering strategies that could extend the therapeutic window for bioscaffolds to repair the damaged brain.
format	article
author	Corina Damian Harmanvir Ghuman Carrinton Mauney Reem Azar Janina Reinartz Stephen F. Badylak Michel Modo
author_facet	Corina Damian Harmanvir Ghuman Carrinton Mauney Reem Azar Janina Reinartz Stephen F. Badylak Michel Modo
author_sort	Corina Damian
title	Post-Stroke Timing of ECM Hydrogel Implantation Affects Biodegradation and Tissue Restoration
title_short	Post-Stroke Timing of ECM Hydrogel Implantation Affects Biodegradation and Tissue Restoration
title_full	Post-Stroke Timing of ECM Hydrogel Implantation Affects Biodegradation and Tissue Restoration
title_fullStr	Post-Stroke Timing of ECM Hydrogel Implantation Affects Biodegradation and Tissue Restoration
title_full_unstemmed	Post-Stroke Timing of ECM Hydrogel Implantation Affects Biodegradation and Tissue Restoration
title_sort	post-stroke timing of ecm hydrogel implantation affects biodegradation and tissue restoration
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/282fbb61b7db4d85a399dbcef1b8e54b
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Post-Stroke Timing of ECM Hydrogel Implantation Affects Biodegradation and Tissue Restoration

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