Bioactive coating of decellularized vascular grafts with a temperature-sensitive VEGF-conjugated hydrogel accelerates autologous endothelialization in vivo.
No ideal small-diameter vascular graft for widespread clinical application has yet been developed and current approaches still suffer from graft failure because of thrombosis or degeneration. Decellularized vascular grafts are a promising strategy as they preserve native vessel architecture while eliminating cell-based antigens and allow for autologous recellularization. In the present study, a functional in vivo rodent aortic transplantation model was used in order to evaluate the benefit of bioactive coating of decellularized vascular grafts with vascular endothelial growth factor (VEGF) conjugated to a temperature-sensitive aliphatic polyester hydrogel (HG). Luminal HG-VEGF coating persistence up to 4 weeks was confirmed in vivo by rhodamine-labelling. Doppler-sonography showed that the grafts were functional for up to 8 weeks in vivo. Histological and immunohistochemical analysis of the explanted grafts after 4 weeks and 8 weeks in vivo demonstrated significantly increased endothelium formation in the HG-VEGF group compared with the control group (luminal surface covered with single-layered endothelium, 4 weeks: 64.8 ± 7.6% vs. 40.4 ± 8.3%, p = 0.025) as well as enhanced media recellularization (absolute cell count, 8 weeks: 22.1 ± 13.0 vs. 3.2 ± 3.6, p = 0.0039). However, HG-VEGF coating also led to increased neo-intimal hyperplasia, resulting in a significantly increased intima-to-media ratio in the perianastomotic regions (intima-to-media ratio, 8 weeks: 1.61 ± 0.17 vs. 0.93 ± 0.09, p = 0.008; HG-VEGF vs. control). The findings indicate that HG-VEGF coating has potential for the development of engineered small-diameter artificial grafts, although further research is needed to prevent neo-intimal hyperplasia. Copyright © 2016 John Wiley & Sons, Ltd.
Department of Cardiovascular Surgery and Research Group for Experimental Surgery, Heinrich Heine University, Medical Faculty, Düsseldorf, Germany.
Makoto
M
Iijima
Department of Cardiovascular Surgery and Research Group for Experimental Surgery, Heinrich Heine University, Medical Faculty, Düsseldorf, Germany.
Hug
H
Aubin
Department of Cardiovascular Surgery and Research Group for Experimental Surgery, Heinrich Heine University, Medical Faculty, Düsseldorf, Germany.
Meike
M
Steinbrink
Department of Cardiovascular Surgery and Research Group for Experimental Surgery, Heinrich Heine University, Medical Faculty, Düsseldorf, Germany.
Franziska
F
Schiffer
Department of Cardiovascular Surgery and Research Group for Experimental Surgery, Heinrich Heine University, Medical Faculty, Düsseldorf, Germany.
Alexander
A
Assmann
Toronto General Research Institute, University Health Network and Department of Surgery, Division of Cardiovascular Surgery, University of Toronto, Toronto, Ontario, Canada.
Richard D
RD
Weisel
Department of Cardiovascular and Thoracic Surgery, Hokkaido University, Graduate school of Medicine, Sapporo, Japan.
Yoshiro
Y
Matsui
Toronto General Research Institute, University Health Network and Department of Surgery, Division of Cardiovascular Surgery, University of Toronto, Toronto, Ontario, Canada.
Ren-Ke
RK
Li
Department of Cardiovascular Surgery and Research Group for Experimental Surgery, Heinrich Heine University, Medical Faculty, Düsseldorf, Germany.
Artur
A
Lichtenberg
Department of Cardiovascular Surgery and Research Group for Experimental Surgery, Heinrich Heine University, Medical Faculty, Düsseldorf, Germany.
Payam
P
Akhyari
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology; D020099:Coated Materials, Biocompatible / Q000494:pharmacology*; D004562:Electrocardiography; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D006334:Heart Function Tests; D020100:Hydrogels / Q000737:chemistry*; D007109:Immunity / Q000187:drug effects; D007249:Inflammation / Q000473:pathology; D008297:Male; D011091:Polyesters / Q000737:chemistry; D017208:Rats, Wistar; D013696:Temperature; D018608:Ultrasonography, Doppler; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology*; D058017:Vascular Grafting
D020099:Coated Materials, Biocompatible; D020100:Hydrogels; D011091:Polyesters; D042461:Vascular Endothelial Growth Factor A
biofunctionalization; de novo endothelialization; decellularized small-diameter aortic grafts; temperature-sensitive hydrogel; vascular endothelial growth factor; vascular tissue engineering