Bioactive coating of decellularized vascular grafts with a temperature-sensitive VEGF-conjugated hydrogel accelerates autologous endothelialization in vivo.

Abstract

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.