Complexation of CXCL12, FGF-2 and VEGF with Heparin Modulates the Protein Release from Alginate Microbeads

Long-term delivery of growth factors and immunomodulatory agents is highly required to support the integrity of tissue in engineering constructs, e.g., formation of vasculature, and to minimize immune response in a recipient. However, for proteins with a net positive charge at the physiological pH,...

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Autores principales:	Edyta Adrian, Dušana Treľová, Elena Filová, Marta Kumorek, Volodymyr Lobaz, Rafal Poreba, Olga Janoušková, Ognen Pop-Georgievski, Igor Lacík, Dana Kubies
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	alginate microbeads heparin CXCL12 VEGF FGF-2 protein release Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/d50c14b571614fd2a96d7be3fd8b3d00
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spelling	oai:doaj.org-article:d50c14b571614fd2a96d7be3fd8b3d002021-11-11T17:07:55ZComplexation of CXCL12, FGF-2 and VEGF with Heparin Modulates the Protein Release from Alginate Microbeads10.3390/ijms2221116661422-00671661-6596https://doaj.org/article/d50c14b571614fd2a96d7be3fd8b3d002021-10-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11666https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Long-term delivery of growth factors and immunomodulatory agents is highly required to support the integrity of tissue in engineering constructs, e.g., formation of vasculature, and to minimize immune response in a recipient. However, for proteins with a net positive charge at the physiological pH, controlled delivery from negatively charged alginate (Alg) platforms is challenging due to electrostatic interactions that can hamper the protein release. In order to regulate such interactions between proteins and the Alg matrix, we propose to complex proteins of interest in this study - CXCL12, FGF-2, VEGF - with polyanionic heparin prior to their encapsulation into Alg microbeads of high content of α-L-guluronic acid units (high-G). This strategy effectively reduced protein interactions with Alg (as shown by model ITC and SPR experiments) and, depending on the protein type, afforded control over the protein release for at least one month. The released proteins retained their in vitro bioactivity: CXCL12 stimulated the migration of Jurkat cells, and FGF-2 and VEGF induced proliferation and maturation of HUVECs. The presence of heparin also intensified protein biological efficiency. The proposed approach for encapsulation of proteins with a positive net charge into high-G Alg hydrogels is promising for controlled long-term protein delivery under in vivo conditions.Edyta AdrianDušana TreľováElena FilováMarta KumorekVolodymyr LobazRafal PorebaOlga JanouškováOgnen Pop-GeorgievskiIgor LacíkDana KubiesMDPI AGarticlealginate microbeadsheparinCXCL12VEGFFGF-2protein releaseBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11666, p 11666 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	alginate microbeads heparin CXCL12 VEGF FGF-2 protein release Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	alginate microbeads heparin CXCL12 VEGF FGF-2 protein release Biology (General) QH301-705.5 Chemistry QD1-999 Edyta Adrian Dušana Treľová Elena Filová Marta Kumorek Volodymyr Lobaz Rafal Poreba Olga Janoušková Ognen Pop-Georgievski Igor Lacík Dana Kubies Complexation of CXCL12, FGF-2 and VEGF with Heparin Modulates the Protein Release from Alginate Microbeads
description	Long-term delivery of growth factors and immunomodulatory agents is highly required to support the integrity of tissue in engineering constructs, e.g., formation of vasculature, and to minimize immune response in a recipient. However, for proteins with a net positive charge at the physiological pH, controlled delivery from negatively charged alginate (Alg) platforms is challenging due to electrostatic interactions that can hamper the protein release. In order to regulate such interactions between proteins and the Alg matrix, we propose to complex proteins of interest in this study - CXCL12, FGF-2, VEGF - with polyanionic heparin prior to their encapsulation into Alg microbeads of high content of α-L-guluronic acid units (high-G). This strategy effectively reduced protein interactions with Alg (as shown by model ITC and SPR experiments) and, depending on the protein type, afforded control over the protein release for at least one month. The released proteins retained their in vitro bioactivity: CXCL12 stimulated the migration of Jurkat cells, and FGF-2 and VEGF induced proliferation and maturation of HUVECs. The presence of heparin also intensified protein biological efficiency. The proposed approach for encapsulation of proteins with a positive net charge into high-G Alg hydrogels is promising for controlled long-term protein delivery under in vivo conditions.
format	article
author	Edyta Adrian Dušana Treľová Elena Filová Marta Kumorek Volodymyr Lobaz Rafal Poreba Olga Janoušková Ognen Pop-Georgievski Igor Lacík Dana Kubies
author_facet	Edyta Adrian Dušana Treľová Elena Filová Marta Kumorek Volodymyr Lobaz Rafal Poreba Olga Janoušková Ognen Pop-Georgievski Igor Lacík Dana Kubies
author_sort	Edyta Adrian
title	Complexation of CXCL12, FGF-2 and VEGF with Heparin Modulates the Protein Release from Alginate Microbeads
title_short	Complexation of CXCL12, FGF-2 and VEGF with Heparin Modulates the Protein Release from Alginate Microbeads
title_full	Complexation of CXCL12, FGF-2 and VEGF with Heparin Modulates the Protein Release from Alginate Microbeads
title_fullStr	Complexation of CXCL12, FGF-2 and VEGF with Heparin Modulates the Protein Release from Alginate Microbeads
title_full_unstemmed	Complexation of CXCL12, FGF-2 and VEGF with Heparin Modulates the Protein Release from Alginate Microbeads
title_sort	complexation of cxcl12, fgf-2 and vegf with heparin modulates the protein release from alginate microbeads
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/d50c14b571614fd2a96d7be3fd8b3d00
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Complexation of CXCL12, FGF-2 and VEGF with Heparin Modulates the Protein Release from Alginate Microbeads

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