Modeling changes in vascular and extracellular matrix integrity that can occur in decellularized kidneys after implantation

Abstract

A method was established to identify alterations in vascular patency and extracellular matrix integrity of decellularized porcine kidney scaffolds. These scaffolds were perfused with blood at physiologically normal (500 and 650 ml/min) and abnormal (200 ml/min) rates. Variations in venous outflow were then assessed over 24 hours. Angiographic data confirmed that standard arterial branching patterns and the integrity of the extracellular matrix were considerably disrupted. Scaffolds subjected to normal arterial perfusion rates observed drops in venous outflow across the 24 hours. These reductions rose from roughly 40% after 12 hours to 60% after 24 hours. At the end of the test period, regardless of the underlying damage that occurred, the kidneys appeared intact on the surface, and there were no apparent signs of clotting. In comparison, venous flow rates decreased by 80 to 100% across the 24 hours in acellular scaffolds subjected to a far lower perfusion rate of 200 ml/min. These kidneys also appeared intact after 24 hours of perfusion, but presented several arterial, venous, and ureteral clots. The results of this study provide insight into circumstances that limit scaffold viability and provide a simplified model to analyze other conditions that can better prepare scaffolds for long-term transplantation.