Peritoneal pre-conditioning impacts long-term vascular graft patency and remodeling.

Abstract

There are questions about how well small-animal models for tissue-engineered vascular grafts (TEVGs) translate to clinical patients. Most TEVG studies used grafting times ≤6months where conduits from generally biocompatible materials like poly(ε-caprolactone) (PCL) perform well. However, longer grafting times can result in significant intimal hyperplasia and calcification. This study tests the hypothesis that differences in pro-inflammatory response from pure PCL conduits will be consequential after long-term grafting. It also tests the long-term benefits of a peritoneal pre-implantation strategy on rodent outcomes. Electrospun conduits with and without peritoneal pre-implantation, and with 0% and 10% (w/w) collagen/PCL, were grafted into abdominal aortae of rats for 10months. This study found that viability of control grafts without pre-implantation was reduced unlike prior studies with shorter grafting times, confirming the relevance of this model. Importantly, pre-implanted grafts had a 100% patency rate. Further, pre-implantation reduced intimal hyperplasia within the graft. Differences in response between pure PCL and collagen/PCL conduits were observed (e.g., fewer CD80+ and CD3+ cells for collagen/PCL), but only pre-implantation had an effect on the overall graft viability. This study demonstrates how long-term grafting in rodent models can better evaluate viability of different TEVGs, and the benefits of the peritoneal pre-implantation step.