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

Adv Healthc Mater. 2024 Jul;13(17):e2303888. doi: 10.1002/adhm.202303888. Epub 2024 Mar 26.

Abstract

Current vascular access options require frequent interventions. In situ tissue engineering (TE) may overcome these limitations by combining the initial success of synthetic grafts with long-term advantages of autologous vessels by using biodegradable grafts that transform into autologous vascular tissue at the site of implantation. Scaffolds (6 mm-Ø) made of supramolecular polycarbonate-bisurea (PC-BU), with a polycaprolactone (PCL) anti-kinking-coil, are implanted between the carotid artery and jugular vein in goats. A subset is bio-functionalized using bisurea-modified-Stromal cell-derived factor-1α (SDF1α) derived peptides and ePTFE grafts as controls. Grafts are explanted after 1 and 3 months, and evaluated for material degradation, tissue formation, compliance, and patency. At 3 months, the scaffold is resorbed and replaced by vascular neo-tissue, including elastin, contractile markers, and endothelial lining. No dilations, ruptures, or aneurysms are observed and grafts are successfully cannulated at termination. SDF-1α-peptide-biofunctionalization does not influence outcomes. Patency is lower in TE grafts (50%) compared to controls (100% patency), predominantly caused by intimal hyperplasia. Rapid remodeling of a synthetic, biodegradable vascular scaffold into a living, compliant arteriovenous fistula is demonstrated in a large animal model. Despite lower patency compared to ePTFE, transformation into autologous and compliant living tissue with self-healing capacity may have long-term advantages.

Keywords: AV shunt; biodegradable supramolecular material; biofunctionalization; goat model; in situ tissue engineering; vascular dialysis access.

MeSH terms

  • Absorbable Implants
  • Animals
  • Arteriovenous Fistula
  • Blood Vessel Prosthesis*
  • Carotid Arteries / surgery
  • Chemokine CXCL12 / metabolism
  • Chemokine CXCL12 / pharmacology
  • Goats*
  • Polyesters / chemistry
  • Tissue Engineering / methods
  • Tissue Scaffolds / chemistry
  • Vascular Patency

Substances

  • Polyesters
  • Chemokine CXCL12