AbstractFunctional artificial vascular meshes from biodegradable polymers have been widely explored for certain tissue engineered meshes. Still, the foreign body reaction and limitation in endothelialization are challenges for such devices. Here, degradable meshes from phase-segregated multiblock copolymers consisting of poly(ε-caprolactone) (PCL) and polydepsipeptide segments are successfully prepared by electrospinning and electrospraying techniques. The pEGFP-ZNF580 plasmid microparticles (MPs-pZNF580) were loaded into the electrospun meshes to enhance endothelialization. These functional meshes were evaluated in vitro and in vivo. The adhesion and proliferation of endothelial cells on the meshes were enhanced in loaded mesh groups. Moreover, the hemocompatibility and the tissue response of the meshes were further tested. The complete tests showed that the vascular meshes modified with MPs-pZNF580 possessed satisfactory performance with an average fiber diameter of 550 ± 160 nm, tensile strength of 27 ± 3 MPa, Young’s modulus of 1. 9 ± 0.2 MPa, water contact angle of 95° ± 2°, relative cell number of 122% ± 1% after 7 days of culture, and low blood platelet adhesion as well as weak inflammatory reactions compared to control groups.