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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MDPI AG
2021-10-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/21/11666 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-10T06:02:04Z |
| format | Article |
| id | doaj.art-d50c14b571614fd2a96d7be3fd8b3d00 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T06:02:04Z |
| publishDate | 2021-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-d50c14b571614fd2a96d7be3fd8b3d002023-11-22T20:55:54ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-10-0122211166610.3390/ijms222111666Complexation of CXCL12, FGF-2 and VEGF with Heparin Modulates the Protein Release from Alginate MicrobeadsEdyta Adrian0Dušana Treľová1Elena Filová2Marta Kumorek3Volodymyr Lobaz4Rafal Poreba5Olga Janoušková6Ognen Pop-Georgievski7Igor Lacík8Dana Kubies9Institute of Macromolecular Chemistry, Czech Academy of Sciences, Heyrovsky sq.2, 162 06 Prague, Czech RepublicPolymer Institute of the Slovak Academy of Sciences, Dubravska cesta 9, 845 41 Bratislava, SlovakiaDepartment of Biomaterials and Tissue Engineering, Institute of Physiology of the Czech Academy of Sciences, Videnska 1083, 142 20 Prague, Czech RepublicInstitute of Macromolecular Chemistry, Czech Academy of Sciences, Heyrovsky sq.2, 162 06 Prague, Czech RepublicInstitute of Macromolecular Chemistry, Czech Academy of Sciences, Heyrovsky sq.2, 162 06 Prague, Czech RepublicInstitute of Macromolecular Chemistry, Czech Academy of Sciences, Heyrovsky sq.2, 162 06 Prague, Czech RepublicInstitute of Macromolecular Chemistry, Czech Academy of Sciences, Heyrovsky sq.2, 162 06 Prague, Czech RepublicInstitute of Macromolecular Chemistry, Czech Academy of Sciences, Heyrovsky sq.2, 162 06 Prague, Czech RepublicPolymer Institute of the Slovak Academy of Sciences, Dubravska cesta 9, 845 41 Bratislava, SlovakiaInstitute of Macromolecular Chemistry, Czech Academy of Sciences, Heyrovsky sq.2, 162 06 Prague, Czech RepublicLong-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.https://www.mdpi.com/1422-0067/22/21/11666alginate microbeadsheparinCXCL12VEGFFGF-2protein release |
| spellingShingle | 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 International Journal of Molecular Sciences alginate microbeads heparin CXCL12 VEGF FGF-2 protein release |
| 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 | alginate microbeads heparin CXCL12 VEGF FGF-2 protein release |
| url | https://www.mdpi.com/1422-0067/22/21/11666 |
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