“…[3] In situ tissue engineering strategies, using acellular, totally or partially degradable, scaffolds that are gradually replaced/remodeled by the host, might represent a viable alternative, joining the main advantage of synthetic grafts (i.e., early puncturability) and the ones of biological substitutes (higher compatibility, remodeling capability, higher patency rates). [4][5][6] In this context, we have previously developed an electrospun hybrid vascular graft based on the combination of natural silk fibroin and synthetic poly-carbonate urethane (a blend named Silkothane), [7] which proved to be a potential candidate for an in situ engineering approach to arteriovenous shunting, due to its favorable mechanical properties, suitable permeability, nonhemolytic character, long clotting time, capability of sustaining adhesion of human umbilical vein endothelial cells in vitro, and early cannulation potential. [8] Indeed, the validation of any in situ tissue engineering products, being their performances so much dependent on the host reaction, needs to face in vivo testing early in the product development pipeline, to assess safety and feasibility of implantation, as well as to preliminarily evaluate the outcomes of grafting in a clinically relevant setting.…”