Cross-linked poly(alkylene citrates) with L-glutathione for vascular tissue engineering: structure–property relationships and cell-type dependent response to oxidative stress

Filip Koper; Dominika Grzywna; Lucie Svobodová; Antonín Sedlář; Libor Kobera; Tomáš Riedel; Zuzana Riedelová; Agata Flis; Hynek Beneš; Elżbieta Pamuła; Lucie Bačáková; Wiktor P. Kasprzyk

doi:10.1039/D4TB02563F

Cross-linked poly(alkylene citrates) with l-glutathione for vascular tissue engineering: structure–property relationships and cell-type dependent response to oxidative stress†

Filip Koper,

^a Dominika Grzywna,^a Lucie Svobodová,

^b Antonín Sedlář,

^b Libor Kobera,

^c Tomáš Riedel,

^d Zuzana Riedelová,^d Agata Flis,^e Hynek Beneš,

^f Elżbieta Pamuła,^e Lucie Bačáková

*^b and Wiktor P. Kasprzyk

*^a

Author affiliations

* Corresponding authors

^a Cracow University of Technology, Faculty of Chemical Engineering and Technology, Department of Biotechnology and Physical Chemistry, 24 Warszawska Str., 31-155 Krakow, Poland
E-mail: wiktor.kasprzyk@pk.edu.pl

^b Czech Academy of Sciences, Institute of Physiology, Department of Biomaterials and Tissue Engineering, 1083 Vídeňská Str., 142 20 Prague, Czech Republic
E-mail: Lucie.Bacakova@fgu.cas.cz

^c Czech Academy of Sciences, Institute of Macromolecular Chemistry, Department of Structural Analysis, Heyrovského nám. 1888/2, 162 00 Prague, Czech Republic

^d Czech Academy of Sciences, Institute of Macromolecular Chemistry, Department of Chemistry and Physics of Surfaces and Biointerfaces, Heyrovského nám. 1888/2, 162 00 Prague, Czech Republic

^e AGH University of Krakow, Faculty of Materials Science and Ceramics, Department of Biomaterials and Composites, 30 Adam Mickiewicza Ave., 30-059 Krakow, Poland

^f Czech Academy of Sciences, Institute of Macromolecular Chemistry, Department of Polymer Processing, Heyrovského nám. 1888/2, 162 00 Prague, Czech Republic

Abstract

Cross-linked poly(alkylene citates) (cPAC) based on 1,6-hexanediol (cPHC) and 1,8-octanediol (cPOC) and modified with 0.4, 0.8 and 1.6% w/w L-glutathione (GSH) were synthesized as potential materials for vascular tissue engineering. The materials prepared at a citric acid : diol molar ratio of 2 : 3 exhibited superior mechanical strength and reduced acidity in comparison to the 1 : 1 materials. All materials exhibited blue fluorescence, which intensity was enhanced with increasing GSH concentration. Conversely, the latter demonstrated marginally enhanced antioxidant properties. The preliminary cell culture tests of the 2 : 3 materials with human adipose tissue stem cells (ASCs) revealed that cPOC did not provide an appropriate environment for cell colonization due to its higher acidity than cPHC. In contrast, cPHC promoted the growth of ASCs and other cell types, including fibroblasts (NHDFs), endothelial cells (HUVECs), and smooth muscle cells (SMCs), at all GSH concentrations, with minimal negative effect on HUVEC and SMC proliferation. The induction of oxidative stress by menadione demonstrated a notable decline in the metabolic activity of both ASCs and NHDFs on cPHCs across all GSH concentrations. However, an incremental protective effect on the cells was observed with increasing GSH concentrations. In contrast, HUVECs and SMCs demonstrated increased metabolic activity, without the protective effect of GSH being observed. Therefore, the findings demonstrate that cell type-specific differences exist in cell response to oxidative stress. Consequently, the addition of antioxidants to the polymer should be guided by the intended cell type for use in vascular reconstruction. Our results also suggest an intrinsic antioxidant activity of cPHC materials and their good hemocompatibility with human blood in vitro.

Journal of Materials Chemistry B

Cross-linked poly(alkylene citrates) with l-glutathione for vascular tissue engineering: structure–property relationships and cell-type dependent response to oxidative stress†

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Cross-linked poly(alkylene citrates) with L-glutathione for vascular tissue engineering: structure–property relationships and cell-type dependent response to oxidative stress

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