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Healing and Angiogenic Properties of Collagen/Chitosan Scaffolds Enriched with Hyperstable FGF2-STAB® Protein: In Vitro, Ex Ovo and In Vivo Comprehensive Evaluation

L. Vojtová, V. Pavliňáková, J. Muchová, K. Kacvinská, J. Brtníková, M. Knoz, B. Lipový, M. Faldyna, E. Göpfert, J. Holoubek, Z. Pavlovský, M. Vícenová, VH. Blahnová, V. Hearnden, E. Filová

. 2021 ; 9 (6) : . [pub] 20210522

Language English Country Switzerland

Document type Journal Article

Persistent link   https://www.medvik.cz/link/bmc21017701

Grant support
17-29874A Ministerstvo Zdravotnictví Ceské Republiky
LO1508 Ministry of Education, Youth and Sports of the Czech Republic
CEITEC VUT/FEKT-J-20-6146 Vysoké Učení Technické v Brně
NV17-29874A MZ0 CEP Register

Wound healing is a process regulated by a complex interaction of multiple growth factors including fibroblast growth factor 2 (FGF2). Although FGF2 appears in several tissue engineered studies, its applications are limited due to its low stability both in vitro and in vivo. Here, this shortcoming is overcome by a unique nine-point mutant of the low molecular weight isoform FGF2 retaining full biological activity even after twenty days at 37 °C. Crosslinked freeze-dried 3D porous collagen/chitosan scaffolds enriched with this hyper stable recombinant human protein named FGF2-STAB® were tested for in vitro biocompatibility and cytotoxicity using murine 3T3-A31 fibroblasts, for angiogenic potential using an ex ovo chick chorioallantoic membrane assay and for wound healing in vivo with 3-month old white New Zealand rabbits. Metabolic activity assays indicated the positive effect of FGF2-STAB® already at very low concentrations (0.01 µg/mL). The angiogenic properties examined ex ovo showed enhanced vascularization of the tested scaffolds. Histological evaluation and gene expression analysis by RT-qPCR proved newly formed granulation tissue at the place of a previous skin defect without significant inflammation infiltration in vivo. This work highlights the safety and biocompatibility of newly developed crosslinked collagen/chitosan scaffolds involving FGF2-STAB® protein. Moreover, these sponges could be used as scaffolds for growing cells for dermis replacement, where neovascularization is a crucial parameter for successful skin regeneration.

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