Complexation of CXCL12, FGF-2 and VEGF with heparin modulates the protein release from alginate microbeads

0547347 - ÚMCH 2022 RIV CH eng J - Journal Article
Adrian, Edyta - Treĺová, D. - Filová, Elena - Kumorek, Marta M. - Lobaz, Volodymyr - Poreba, Rafal - Janoušková, Olga - Pop-Georgievski, Ognen - Lacík, I. - Kubies, Dana
Complexation of CXCL12, FGF-2 and VEGF with heparin modulates the protein release from alginate microbeads.
International Journal of Molecular Sciences. Roč. 22, č. 21 (2021), č. článku 11666. E-ISSN 1422-0067
R&D Projects: GA MZd(CZ) NV16-28254A; GA MZd(CZ) NV19-02-00068; GA ČR(CZ) GA20-08679S
Institutional support: RVO:61389013 ; RVO:67985823
Keywords : alginate microbeads * heparin * CXCL12
OECD category: Polymer science; Biomaterials (as related to medical implants, devices, sensors) (FGU-C)
Impact factor: 6.208, year: 2021
Method of publishing: Open access
https://www.mdpi.com/1422-0067/22/21/11666

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.
Permanent Link: http://hdl.handle.net/11104/0323866