Sulfation degree not origin of chondroitin sulfate derivatives modulates keratinocyte response

Luisana Corsuto; Sandra Rother; Linda Koehler; Emiliano Bedini; Stephanie Moeller; Matthias Schnabelrauch; Vera Hintze; Chiara Schiraldi; Dieter Scharnweber

doi:10.1016/j.carbpol.2018.02.072

Sulfation degree not origin of chondroitin sulfate derivatives modulates keratinocyte response

Carbohydr Polym. 2018 Jul 1:191:53-64. doi: 10.1016/j.carbpol.2018.02.072. Epub 2018 Mar 1.

Authors

Luisana Corsuto¹, Sandra Rother², Linda Koehler², Emiliano Bedini³, Stephanie Moeller⁴, Matthias Schnabelrauch⁴, Vera Hintze², Chiara Schiraldi⁵, Dieter Scharnweber⁶

Affiliations

¹ Department of Experimental Medicine, Section of Biotechnology, Second University of Naples, Italy.
² Technische Universitaet Dresden, Institute of Materials Science, Max Bergmann Center of Biomaterials, D-01069 Dresden, Germany.
³ Department of Chemical Sciences, University of Naples Federico II, Complesso Universitario Monte S. Angelo, via Cintia 4, I-80126 Napoli, Italy.
⁴ Biomaterials Department, INNOVENT e.V., D-07745 Jena, Germany.
⁵ Department of Experimental Medicine, Section of Biotechnology, Second University of Naples, Italy. Electronic address: chiara.schiraldi@unicampania.it.
⁶ Technische Universitaet Dresden, Institute of Materials Science, Max Bergmann Center of Biomaterials, D-01069 Dresden, Germany. Electronic address: dieter.scharnweber@tu-dresden.de.

PMID: 29661321
DOI: 10.1016/j.carbpol.2018.02.072

Abstract

Chondroitin sulfate (CS) sulfation-dependently binds transforming growth factor-β1 (TGF-β1) and chronic wounds often accompany with epidermal hyperproliferation due to downregulated TGF-β signaling. However, the impact of CS on keratinocytes is unknown. Especially biotechnological-chemical strategies are promising to replace animal-derived CS. Thus, this study aims to evaluate the effects of CS derivatives on the interaction with vascular endothelial growth factor-A (VEGF-A) and on keratinocyte response. Over-sulfated CS (sCS3) interacts stronger with VEGF-A than CS. Furthermore, collagen coatings with CS variants are prepared by in vitro fibrillogenesis. Stability analyses demonstrate that collagen is firmly integrated, while the fibril diameters decrease with increasing sulfation degree. CS variants sulfation-dependently decelerate keratinocyte (HaCaT) migration and proliferation in a scratch assay. HaCaT cultured on sCS3-containing coatings produced increased amounts of solute active TGF-β1 which could be translated into biomaterials able to decrease epidermal hyperproliferation in chronic wounds. Overall, semi-synthetic and natural CS yield to comparable responses.

Keywords: Artificial extracellular matrix; Chondroitin sulfate; Inflammatory cytokines; Matrix metalloproteinase; Sulfation degree; Vascular endothelial growth factor.