Engineering of fibrin-based functional and implantable small-diameter blood vessels

Abstract

Conclusion: Fibrin can serve as an appropriate scaffold for engineering small caliber blood vessels that have both vasoreactivity and considerable mechanical strength. Summary: Currently, autogenous tissue, such as saphenous vein or radial artery, is the gold standard for an arterial substitute for a small caliber vessel. The authors engineered implantable small diameter blood vessels using a fibrin gel with embedded ovin smooth muscle and endothelial cells. Fibrin gels can achieve high seeding of smooth muscle and endothelial cells with uniform cellular distribution. Fibrin might thus be an alternative to collagen as a scaffold for an engineered small caliber vessel. The fibrin matrix based tissue engineered vessels developed in this study exhibited considerable reactivity in response to both receptor and non-receptor mediated dilators and vasoconstrictors. Apoprotinin when added to fibrin gel preparation at moderate concentrations increased mechanical strength of the engineered blood vessel but decreased vascular activity. Mechanical strength and reactivity of the blood vessels were comparable to those of native veins. The mechanical strength of the fibrin-based blood vessels was sufficiently strong to withstand implantation into the jugular veins of lambs. Late microscopic analysis indicated tissue engineered vessels integrated well to native tissue while demonstrating similar flow rates and patency as native vessels. At fifteen weeks after implantation the fibrin-based vessels demonstrated matrix remodeling with production of both elastin and collagen fibers and orientation of smooth muscle cells perpendicular to the direction of blood flow. Comment: One of the “Holy Grails” of vascular surgery is the development of a commercially available, off the shelf, highly effective arterial substitute for a small caliber vessel. This study indicates that use of a fibrin scaffold for development of such an arterial substitute is a potentially fertile line of inquiry. These engineered vessels appear to remain patent when implanted, seamlessly integrate into native vessel, and display vaso-reactivity similar to normal veins. Obviously, development of a commercial product is many years away. Nevertheless, it is good to know that, even after the failure of endothelial seeding of prosthetic grafts, investigators are still pursuing the development of a small caliber arterial substitute.