Insight on the endothelialization of small silk-based tissue-engineered vascular grafts

Along with an increased incidence of cardiovascular diseases, there is a strong need for small-diameter vascular grafts. Silk has been investigated as a biomaterial to develop such grafts thanks to different processing options. Endothelialization was shown to be extremely important to ensure graft patency and there is ongoing research on the development and behavior of endothelial cells on vascular tissue-engineered scaffolds. This article reviews the endothelialization of silk-based scaffolds processed throughout the years as silk non-woven nets, films, gel spun, electrospun, or woven scaffolds. Encouraging results were reported with these scaffolds both in vitro and in vivo when implanted in small- to middle-sized animals. The use of coatings and heparin or sulfur to enhance, respectively, cell adhesion and scaffold hemocompatibility is further presented. Bioreactors also showed their interest to improve cell adhesion and thus promoting in vitro pre-endothelialization of grafts even though they are still not systematically used. Finally, the importance of the animal models used to study the right mechanism of endothelialization is discussed.