Semi-degradable biomimetic double-layer small diameter vascular graft for arteriovenous fistula in large animals

A double layer small diameter vascular graft (SDVG) was fabricated by sequential electrospinning. The inner layer was composed by three kinds of biodegradable poly (ε-caprolactone) (PCL) fibers with three different molecular weights to induce endothelial regeneration and the outer layer comprised non-degradable thermoplastic polyurethane (TPU) fibers and PCL fibers with the numerical molecular weight of 80,000 g/mol to provide long-term mechanical support. The SDVG was further heparinized through "erosion and graft" strategy. The surface heparin content, the clotting time and the mechanical properties were evaluated in vitro. Then, the double layer SDVG was implanted into the sheep for six months as the arteriovenous fistula connecting carotid artery and jugular vein. The Doppler ultrasonic measurement and angiography showed the patency of the transplanted SDVGs and the in situ puncture test exhibited the potential of the SDVG for hemodialysis. H&E and Masson staining characterized the remodeling of the inner layer, whereas Safranin O and von Kossa staining demonstrated the regeneration of extracellular matrix and the absence of the calcification in the implanted SDVG. More importantly, the perfect regeneration of endothelium on the lumen of the SDVG was proven by CD31 staining. Consequently, the as-prepared SDVG showed the potential to be the artificial arteriovenous fistula in the clinic.