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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: Adrian, Edyta, Treľová, Dušana, Filová, Elena, Kumorek, Marta, Lobaz, Volodymyr, Poreba, Rafal, Janoušková, Olga, Pop-Georgievski, Ognen, Lacík, Igor, Kubies, Dana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8583835/
https://www.ncbi.nlm.nih.gov/pubmed/34769095
http://dx.doi.org/10.3390/ijms222111666
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author Adrian, Edyta
Treľová, Dušana
Filová, Elena
Kumorek, Marta
Lobaz, Volodymyr
Poreba, Rafal
Janoušková, Olga
Pop-Georgievski, Ognen
Lacík, Igor
Kubies, Dana
author_facet Adrian, Edyta
Treľová, Dušana
Filová, Elena
Kumorek, Marta
Lobaz, Volodymyr
Poreba, Rafal
Janoušková, Olga
Pop-Georgievski, Ognen
Lacík, Igor
Kubies, Dana
author_sort Adrian, Edyta
collection PubMed
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.
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spelling pubmed-85838352021-11-12 Complexation of CXCL12, FGF-2 and VEGF with Heparin Modulates the Protein Release from Alginate Microbeads Adrian, Edyta Treľová, Dušana Filová, Elena Kumorek, Marta Lobaz, Volodymyr Poreba, Rafal Janoušková, Olga Pop-Georgievski, Ognen Lacík, Igor Kubies, Dana Int J Mol Sci Article 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. MDPI 2021-10-28 /pmc/articles/PMC8583835/ /pubmed/34769095 http://dx.doi.org/10.3390/ijms222111666 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Adrian, Edyta
Treľová, Dušana
Filová, Elena
Kumorek, Marta
Lobaz, Volodymyr
Poreba, Rafal
Janoušková, Olga
Pop-Georgievski, Ognen
Lacík, Igor
Kubies, Dana
Complexation of CXCL12, FGF-2 and VEGF with Heparin Modulates the Protein Release from Alginate Microbeads
title 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_short 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
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8583835/
https://www.ncbi.nlm.nih.gov/pubmed/34769095
http://dx.doi.org/10.3390/ijms222111666
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