Enhanced endothelialization for developing artificial vascular networks with a natural vessel mimicking the luminal surface in scaffolds

Large tissue regeneration remains problematic because of a lack of oxygen and nutrient supply. An attempt to meet the metabolic needs of cells has been made by preforming branched vascular networks within a scaffold to act as channels for mass transport. When constructing functional vascular networks with channel patency, emphasis should be placed on anti-thrombogenic surface issues. The aim of this study was to develop a rapid endothelialization method for creating an anti-thrombogenic surface mimicking the natural vessel wall in the artificial vascular networks. Shear stress preconditioning and scaffold surface modification were investigated as effective approaches for promoting biomaterial endothelialization. We found that a transient increase in shear stress at the appropriate time is key to enhancing endothelialization. Moreover, surface modification with bioactive materials such as collagen and recombinant mussel adhesive protein fused with arginine–glycine–aspartic acid peptide (MAP-RGD) showed a synergetic effect with shear stress preconditioning. Platelet adhesion tests demonstrated the anti-thrombogenic potential of MAP-RGD itself without endothelialization. The rapid endothelialization method established in this study can be easily applied to preformed artificial vascular networks in porous scaffolds. Development of artificial vascular networks with an anti-thrombogenic luminal surface will open up a new chapter in tissue engineering and regenerative medicine.