An in vivo study on endothelialized vascular grafts produced by autologous biotubes and adipose stem cells (ADSCs)

Abstract

Currently, commercial synthetic vascular grafts made from Dacron and ePTFE for small-diameter, vascular applications (<6 mm) show limited reendothelization and are less compliant, often resulting in thrombosis and intimal hyperplasia. Although good blood compatibility can be achieved in autologous arteries and veins, the number of high quality harvest sites is limited, and the grafts are size-mismatched for use in the fistula or cardiovascular bypass surgery; thus, alternative small graft substitutes must be developed. A biotube is an in vivo, tissue-engineered approach for the growth of autologous grafts through the subcutaneous implantation of an inert rod through the inflammation process. In the present study, we embedded silicone rods with a diameter of 2 mm into the dorsal subcutaneous tissue of rabbits for 4 weeks to grow biotubes. The formation of functional endothelium cells aligned on the inner wall surface was achieved by seeding with adipose stem cells (ADSCs). The ADSCs-seeded biotubes were implanted into the carotid artery of rabbits for more than 1 month, and the patency rates and remodeling of endothelial cells were observed by angiography and fluorescence staining, respectively. Finally, the mechanical properties of the biotube were also evaluated. The fluorescence staining results showed that the ADSCs differentiated not only into endothelia cells but also into smooth muscle cells. Moreover, the patency of the ADSCs-seeded biotube remained high for at least 5 months. These small-sized ADSCs-seeded vascular biotubes may decrease the rate of intimal hyperplasia during longer implantation times and have potential clinical applications in the future.