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

Autoři	VOJTOVA Lucy PAVLINAKOVA Veronika MUCHOVA Johana KACVINSKA Katarina BRTNIKOVA Jana KNOZ Martin LIPOVÝ Břetislav FALDYNA Martin GOPFERT Eduard HOLOUBEK Jakub PAVLOVSKÝ Zdeněk VICENOVA Monika HEFKA BLAHNOVA Veronika HEARNDEN Vanessa FILOVA Eva
Rok publikování	2021
Druh	Článek v odborném periodiku
Časopis / Zdroj	BIOMEDICINES
Fakulta / Pracoviště MU	Lékařská fakulta
Citace
www	https://www.mdpi.com/2227-9059/9/6/590
Doi	http://dx.doi.org/10.3390/biomedicines9060590
Klíčová slova	collagen; chitosan; scaffold; FGF2; skin regeneration; tissue engineering
Popis	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 degrees C. Crosslinked freeze-dried 3D porous collagen/chitosan scaffolds enriched with this hyper stable recombinant human protein named FGF2-STAB(R) 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(R) already at very low concentrations (0.01 mu g/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(R) 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.