Endothelialized and preconditioned natural umbilical arteries with long term patency open the route for future human uses.

The major challenge of vascular tissue engineering is to develop a small calibre vascular graft with a high patency rate. In native vessels, the thrombosis is prevented by the endothelium located at the luminal site of the vessel. The aim of this study was to develop a resistant endothelial lining on the inner surface of vascular graft using a polyelectrolyte multilayers (PEM) film. Umbilical arteries were de-endothelialized, coated with 3.5 bilayers of poly(styrene sulfonate) (PSS)/poly(allylamine hydrochloride) (PAH) and then cellularized with endothelial cells. The grafts were cultured for a week in static condition and preconditioned by exposure to a shear stress of at 1 Pa for three hours before implantation on the rabbit carotid site. Histological and confocal microscopy in vitro investigations showed that PEMs films improve cell adhesion and retention on the luminal surface after shear stress preconditioning. In vivo Doppler data showed that graft preconditioning is a crucial factor for graft patency. Indeed, preconditioned grafts remained over the whole experimental period, whereas unpreconditioned grafts were obstructed after only one week of implantation. These results open the route toward the development of a new generation of vascular substitutes having a long term patency.

Mechanical and biological performances of new scaffolds made of collagen hydrogels and fibroin microfibers for vascular tissue engineering.

A microstructured composite material made of collagen hydrogel (matrix) and silk fibroin microfibers (randomly oriented reinforcing fibers) is investigated in order to conjugate the mechanical resistance of fibroin with the suitable biological performance of collagen to design new scaffolds for vascular tissue engineering. Results show that fibroin microfibers and collagen fibrils have suitable interfacial adhesion, and the scaffold exhibits improved mechanical properties if compared with a pure collagen hydrogel. Furthermore, the overall biological performance is improved.

The importance of the effect of shear stress on endothelial cells in determining the performance of hemoglobin based oxygen carriers.

The lack of blood donations and the threat of infections from blood and blood products have led to extensive research into the development of blood substitutes. The latest generation of hemoglobin based oxygen carriers (HBOC) has been shown to induce side effects like hypertension, vasoconstriction, inflammation and oxidative stress. HBOC are able to restore volemia and transport oxygen after a hemorrhagic shock, the reperfusion leading to the restoration of the blood flow in vessels. We propose an innovative approach, more closely emulating clinical situations, to assess the impact of HBOC perfusion on endothelial cells (EC) in vitro. Through this approach we quantified levels of oxidative stress, vasoactive factors and inflammation. EC were cultivated under a laminar flow to reproduce the return of shear stress (SS) during the reperfusion. We showed that heme oxygenase I transcription correlated with changes in oxidatively modified heme and methemoglobin; all were lower under SS. SS induced increased nitric oxide production, which may have implications for the mechanism of in vivo vasoconstriction and hypertension. E-selectin changes under SS were greater than those of ICAM-1. Our results demonstrate how it is essential to include SS in assays attempting to understand the potential vascular side effects of HBOC perfusion.