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Bioactive coating of decellularized vascular grafts with a temperature‐sensitive VEGF‐conjugated hydrogel accelerates autologous endothelialization in vivo
Author(s) -
Iijima Makoto,
Aubin Hug,
Steinbrink Meike,
Schiffer Franziska,
Assmann Alexander,
Weisel Richard D.,
Matsui Yoshiro,
Li RenKe,
Lichtenberg Artur,
Akhyari Payam
Publication year - 2018
Publication title -
journal of tissue engineering and regenerative medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.835
H-Index - 72
eISSN - 1932-7005
pISSN - 1932-6254
DOI - 10.1002/term.2321
Subject(s) - decellularization , in vivo , intimal hyperplasia , vascular endothelial growth factor , angiogenesis , transplantation , pathology , chemistry , neovascularization , biomedical engineering , tissue engineering , medicine , surgery , cancer research , vegf receptors , biology , microbiology and biotechnology , smooth muscle
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.