Sulfated levan from Halomonas smyrnensis as a bioactive, heparin-mimetic glycan for cardiac tissue engineering applications.
Chemical derivatives of levan from Halomonas smyrnensis AAD6(T) with low, medium and high levels of sulfation were synthesized and characterized by FTIR and 2D-NMR. Sulfated levan samples were found to exhibit anticoagulation activity via the intrinsic pathway like heparin in a dose-dependent manner. Exceptionally high heparin equivalent activity of levan sulfate was shown to proceed via thrombin inhibition where decreased Factor Xa activity with increasing concentration was observed in antithrombin tests and above a certain concentration, levan sulfate showed a better inhibitor activity than heparin. In vitro experimental results were then verified in silico by docking studies using equilibrium structures obtained by molecular dynamic simulations and results suggested a sulfation dependent binding mechanism. With its high biocompatibility and heparin mimetic activity, levan sulfate can be considered as a suitable functional biomaterial to design biologically active, functionalized, thin films and engineered smart scaffolds for cardiac tissue engineering applications.
IBSB, Department of Bioengineering, Marmara University, Istanbul, Turkey.
Merve
M
Erginer
IBSB, Department of Bioengineering, Marmara University, Istanbul, Turkey.
Ayca
A
Akcay
Department of Chemical Engineering, Yeditepe University, Istanbul, Turkey.
Binnaz
B
Coskunkan
IBSB, Department of Bioengineering, Marmara University, Istanbul, Turkey.
Tunc
T
Morova
Center for Materials, Devices and Integrated Systems, Rensselaer Polytechnic Institute, Troy, NY, USA.
Deniz
D
Rende
Department of Chemical Engineering, Yeditepe University, Istanbul, Turkey.
Seyda
S
Bucak
Department of Chemical and Biological Engineering, Rensselaer Polytechnic Institute, Troy, NY, USA.
Nihat
N
Baysal
Department of Materials Science and Engineering, Rensselaer Polytechnic Institute, Troy, NY, USA.
Rahmi
R
Ozisik
Department of Chemical Engineering, Marmara University, Istanbul, Turkey; TUBITAK-UME, Chemistry Group Laboratories, Kocaeli, Turkey.
Mehmet S
MS
Eroglu
Medeniyet University Medical School, Department of Cardiology, Istanbul, Turkey.
Mehmet
M
Agirbasli
IBSB, Department of Bioengineering, Marmara University, Istanbul, Turkey. Electronic address: ebru.toksoy@marmara.edu.tr.
Ebru
E
Toksoy Oner
D000818:Animals; D000925:Anticoagulants / Q000737:chemistry / Q000494:pharmacology; D040761:Biomimetic Materials / Q000737:chemistry / Q000494:pharmacology; D002236:Carbohydrate Conformation; D005630:Fructans / Q000737:chemistry* / Q000494:pharmacology*; D020632:Halomonas / Q000737:chemistry*; D006321:Heart / Q000187:drug effects; D006493:Heparin / Q000378:metabolism*; D006801:Humans; D008422:Materials Testing; D051379:Mice; D056004:Molecular Dynamics Simulation; D009206:Myocardium / Q000166:cytology*; D013431:Sulfates / Q000737:chemistry*; D013917:Thrombin / Q000037:antagonists & inhibitors; D023822:Tissue Engineering
D000925:Anticoagulants; D005630:Fructans; D013431:Sulfates; D006493:Heparin; C072599:levan; D013917:Thrombin
Anticoagulant activity; Halomonas smyrnensis; Heparin mimetics; Levan; Sulfation