Peritoneal pre-conditioning reduces macrophage marker expression in collagen-containing engineered vascular grafts

Engineered vascular grafts have shown promise as arteriovenous shunts, but they have not yet progressed to clinical trials for coronary arteries <4 mm in diameter such as the coronary arteries. Control over initial biomaterial properties and remodeling are necessary to generate viable grafts. In this study, we blended collagen with a synthetic material, poly(ε-caprolactone), to modulate the post-grafting inflammatory response while avoiding aneurysmal-like dilation and failure that can occur with pure collagen grafts. We also used pre-implantation in an "in vivo bioreactor" to recruit autologous cells and improve patency after grafting. Electrospun conduits were pre-implanted within rat peritoneal cavities and then grafted autologously into abdominal aortae. Conduit collagen percentages and pre-implantation were tested for their impact on graft remodeling and patency. Burst pressures >2000 mmHg, reproducible expansion with systole/diastole, and maintenance of mechanical integrity were observed. More importantly, peritoneal pre-implantation reduced overall lipid oxidation, intimal layer thickness, and expression of an M1 macrophage marker. The condition with the most collagen, 25%, exhibited the lowest expression of macrophage markers but also resulted in a thicker intimal layer. Overall, the 10% collagen/PCL with peritoneal pre-implantation condition appeared to exhibit the best combination of responses, and may result in improved clinical graft viability. Statement of significance This manuscript describes a rodent study to systematically determine the benefits of both pre-implantation in the peritoneal cavity and specific ratios of collagen on engineered vascular graft viability. We show that pre-implantation had a significant benefit, including decreasing the expression of macrophage markers and reducing lipid oxidation after grafting. This study is the first time that the benefits of peritoneal pre-implantation have been compared to an "off the shelf," directly grafted control condition. We also demonstrated the importance of specific collagen ratio on the response after grafting. Overall, we feel that this article will be of interest to the field and it has the potential to address a significant clinical need: a graft for coronary arteries <4 mm in diameter.