Off-the-Shelf Synthetic Biodegradable Grafts Transform In Situ into a Living Arteriovenous Fistula in a Large Animal Model

This study demonstrates the in situ transformation of a synthetic, cell-free, biodegradable vascular graft into a living, compliant arteriovenous fistula (AVF) in goats. The scaffold comprised electrospun polycarbonate-bisurea (PC-BU) with a 3D-printed polycaprolactone (PCL) anti-kink coil (6 mm diameter). After 3 months, grafts were largely resorbed and replaced by autologous tissue containing elastin, contractile αSMA⁺ smooth muscle cells, and endothelial lining. Mechanical testing revealed an estimated modulus comparable to native carotids, while ePTFE controls remained significantly stiffer. No calcification or fibrosis was detected. Macrophage polarization favored M2 (CD163⁺) over M1 (iNOS⁺), indicating regenerative remodeling. Though 3-month patency was 50% (vs 100% for ePTFE), all grafts were cannulatable with rapid hemostasis. The study validates the feasibility of off-the-shelf vascular grafts that remodel into living, self-healing conduits within 3 months.