A bio-inspired screwed small-diameter vascular graft for endotheliazation and arterial regeneration

Abstract

The frequent failures of small-diameter vascular grafts (SDVGs) mainly result from thrombosis and insufficient endothelialization. Despite recent biochemical modification strategies aiming to enhance long-term patency, the challenges of suppressing thrombosis and promoting rapid endothelialization persist. We thus designed a biomimetic three-layer flexible vascular graft scaffold. This scaffold precisely replicates the nonlinear mechanical responses of vascular tissues and promotes vascular regeneration by minimizing the mechanical mismatch between the graft and the host. The biomimetic flexible SDVG scaffold comprises a screwed inner layer, a middle fabric layer, and a Polyethylene terephthalate (PET) helical coil. It shows excellent bending resistance and resilience, reducing thrombosis formation caused by impaired blood flow during bending. Moreover, this scaffold notably improves the adhesion, spreading, proliferation, and elongation of endothelial cells, facilitating luminal remodeling and maintaining long-term patency through its intimal topography. In vivo studies demonstrate that the endothelial layer forms within three months of implantation, ensuring long-term patency. By three months after implantation, both the endothelial and smooth muscle layers are regenerated, developing hierarchical microstructures and compositions similar to those of native vessels. The biomimetic flexible vascular graft with screwed structures exhibits excellent bending resistance and enhanced vascular remodeling, thereby promoting blood vessel regeneration and showing strong potential for clinical translation.