Covalent linkage of sulfated hyaluronan to the collagen scaffold Mucograft® enhances scaffold stability and reduces proinflammatory macrophage activation in vivo

Sulfated glycosaminoglycans (sGAG) show interaction with biological mediator proteins. Although collagen-based biomaterials are widely used in clinics, their combination with high-sulfated hyaluronan (sHA3) is unexplored. This study aims to functionalize a collagen-based scaffold (Mucograft®) with s...

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Autores principales:	Sarah Al-Maawi, Sandra Rother, Norbert Halfter, Karen M. Fiebig, Juliane Moritz, Stephanie Moeller, Matthias Schnabelrauch, Charles James Kirkpatrick, Robert Sader, Hans-Peter Wiesmann, Dieter Scharnweber, Vera Hintze, Shahram Ghanaati
Formato:	article
Lenguaje:	EN
Publicado:	KeAi Communications Co., Ltd. 2022
Materias:	Sulfated hyaluronan Collagen Wound healing Cellular reaction Multinucleated giant cells Materials of engineering and construction. Mechanics of materials TA401-492 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/221eb601dcf94198ac2ba521f2f773dd
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spelling	oai:doaj.org-article:221eb601dcf94198ac2ba521f2f773dd2021-11-04T04:35:06ZCovalent linkage of sulfated hyaluronan to the collagen scaffold Mucograft® enhances scaffold stability and reduces proinflammatory macrophage activation in vivo2452-199X10.1016/j.bioactmat.2021.06.008https://doaj.org/article/221eb601dcf94198ac2ba521f2f773dd2022-02-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2452199X21002929https://doaj.org/toc/2452-199XSulfated glycosaminoglycans (sGAG) show interaction with biological mediator proteins. Although collagen-based biomaterials are widely used in clinics, their combination with high-sulfated hyaluronan (sHA3) is unexplored. This study aims to functionalize a collagen-based scaffold (Mucograft®) with sHA3 via electrostatic (sHA3/PBS) or covalent binding to collagen fibrils (sHA3+EDC/NHS). Crosslinking without sHA3 was used as a control (EDC/NHS Ctrl). The properties of the sHA3-functionalized materials were characterized. In vitro growth factor and cytokine release after culturing with liquid platelet-rich fibrin was performed by means of ELISA. The cellular reaction to the biomaterials was analyzed in a subcutaneous rat model. The study revealed that covalent linking of sHA3 to collagen allowed only a marginal release of sHA3 over 28 days in contrast to electrostatically bound sHA3. sHA3+EDC/NHS scaffolds showed reduced vascular endothelial growth factor (VEGF), transforming growth factor beta 1 (TGF-β1) and enhanced interleukin-8 (IL-8) and epithelial growth factor (EGF) release in vitro compared to the other scaffolds. Both sHA3/PBS and EDC/NHS Ctrl scaffolds showed a high proinflammatory reaction (M1: CD-68+/CCR7+) and induced multinucleated giant cell (MNGC) formation in vivo. Only sHA3+EDC/NHS scaffolds reduced the proinflammatory macrophage M1 response and did not induce MNGC formation during the 30 days. SHA3+EDC/NHS scaffolds had a stable structure in vivo and showed sufficient integration into the implantation region after 30 days, whereas EDC/NHS Ctrl scaffolds underwent marked disintegration and lost their initial structure. In summary, functionalized collagen (sHA3+EDC/NHS) modulates the inflammatory response and is a promising biomaterial as a stable scaffold for full-thickness skin regeneration in the future.Sarah Al-MaawiSandra RotherNorbert HalfterKaren M. FiebigJuliane MoritzStephanie MoellerMatthias SchnabelrauchCharles James KirkpatrickRobert SaderHans-Peter WiesmannDieter ScharnweberVera HintzeShahram GhanaatiKeAi Communications Co., Ltd.articleSulfated hyaluronanCollagenWound healingCellular reactionMultinucleated giant cellsMaterials of engineering and construction. Mechanics of materialsTA401-492Biology (General)QH301-705.5ENBioactive Materials, Vol 8, Iss , Pp 420-434 (2022)
institution	DOAJ
collection	DOAJ
language	EN
topic	Sulfated hyaluronan Collagen Wound healing Cellular reaction Multinucleated giant cells Materials of engineering and construction. Mechanics of materials TA401-492 Biology (General) QH301-705.5
spellingShingle	Sulfated hyaluronan Collagen Wound healing Cellular reaction Multinucleated giant cells Materials of engineering and construction. Mechanics of materials TA401-492 Biology (General) QH301-705.5 Sarah Al-Maawi Sandra Rother Norbert Halfter Karen M. Fiebig Juliane Moritz Stephanie Moeller Matthias Schnabelrauch Charles James Kirkpatrick Robert Sader Hans-Peter Wiesmann Dieter Scharnweber Vera Hintze Shahram Ghanaati Covalent linkage of sulfated hyaluronan to the collagen scaffold Mucograft® enhances scaffold stability and reduces proinflammatory macrophage activation in vivo
description	Sulfated glycosaminoglycans (sGAG) show interaction with biological mediator proteins. Although collagen-based biomaterials are widely used in clinics, their combination with high-sulfated hyaluronan (sHA3) is unexplored. This study aims to functionalize a collagen-based scaffold (Mucograft®) with sHA3 via electrostatic (sHA3/PBS) or covalent binding to collagen fibrils (sHA3+EDC/NHS). Crosslinking without sHA3 was used as a control (EDC/NHS Ctrl). The properties of the sHA3-functionalized materials were characterized. In vitro growth factor and cytokine release after culturing with liquid platelet-rich fibrin was performed by means of ELISA. The cellular reaction to the biomaterials was analyzed in a subcutaneous rat model. The study revealed that covalent linking of sHA3 to collagen allowed only a marginal release of sHA3 over 28 days in contrast to electrostatically bound sHA3. sHA3+EDC/NHS scaffolds showed reduced vascular endothelial growth factor (VEGF), transforming growth factor beta 1 (TGF-β1) and enhanced interleukin-8 (IL-8) and epithelial growth factor (EGF) release in vitro compared to the other scaffolds. Both sHA3/PBS and EDC/NHS Ctrl scaffolds showed a high proinflammatory reaction (M1: CD-68+/CCR7+) and induced multinucleated giant cell (MNGC) formation in vivo. Only sHA3+EDC/NHS scaffolds reduced the proinflammatory macrophage M1 response and did not induce MNGC formation during the 30 days. SHA3+EDC/NHS scaffolds had a stable structure in vivo and showed sufficient integration into the implantation region after 30 days, whereas EDC/NHS Ctrl scaffolds underwent marked disintegration and lost their initial structure. In summary, functionalized collagen (sHA3+EDC/NHS) modulates the inflammatory response and is a promising biomaterial as a stable scaffold for full-thickness skin regeneration in the future.
format	article
author	Sarah Al-Maawi Sandra Rother Norbert Halfter Karen M. Fiebig Juliane Moritz Stephanie Moeller Matthias Schnabelrauch Charles James Kirkpatrick Robert Sader Hans-Peter Wiesmann Dieter Scharnweber Vera Hintze Shahram Ghanaati
author_facet	Sarah Al-Maawi Sandra Rother Norbert Halfter Karen M. Fiebig Juliane Moritz Stephanie Moeller Matthias Schnabelrauch Charles James Kirkpatrick Robert Sader Hans-Peter Wiesmann Dieter Scharnweber Vera Hintze Shahram Ghanaati
author_sort	Sarah Al-Maawi
title	Covalent linkage of sulfated hyaluronan to the collagen scaffold Mucograft® enhances scaffold stability and reduces proinflammatory macrophage activation in vivo
title_short	Covalent linkage of sulfated hyaluronan to the collagen scaffold Mucograft® enhances scaffold stability and reduces proinflammatory macrophage activation in vivo
title_full	Covalent linkage of sulfated hyaluronan to the collagen scaffold Mucograft® enhances scaffold stability and reduces proinflammatory macrophage activation in vivo
title_fullStr	Covalent linkage of sulfated hyaluronan to the collagen scaffold Mucograft® enhances scaffold stability and reduces proinflammatory macrophage activation in vivo
title_full_unstemmed	Covalent linkage of sulfated hyaluronan to the collagen scaffold Mucograft® enhances scaffold stability and reduces proinflammatory macrophage activation in vivo
title_sort	covalent linkage of sulfated hyaluronan to the collagen scaffold mucograft® enhances scaffold stability and reduces proinflammatory macrophage activation in vivo
publisher	KeAi Communications Co., Ltd.
publishDate	2022
url	https://doaj.org/article/221eb601dcf94198ac2ba521f2f773dd
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Covalent linkage of sulfated hyaluronan to the collagen scaffold Mucograft® enhances scaffold stability and reduces proinflammatory macrophage activation in vivo

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