Composite fibrin scaffolds increase mechanical strength and preserve contractility of tissue engineered blood vessels.

Abstract

We recently demonstrated that fibrin-based tissue engineered blood vessels (TEV) exhibited vascular reactivity, matrix remodeling and sufficient strength for implantation into the veins of an ovine animal model, where they remained patent for 15 weeks. Here we present an approach to improve the mechanical properties of fibrin-based TEV and examine the relationship between mechanical strength and smooth muscle cell (SMC) function. To this end, we prepared TEV that were composed of two layers: a cellular layer containing SMC embedded in fibrin hydrogel to provide contractility and matrix remodeling; and a second cell-free fibrin layer composed of high concentration fibrinogen to provide mechanical strength. The ultimate tensile force of double-layered TEV increased with FBG concentration in the cell-free layer in a dose-dependent manner. Double-layered TEV exhibited burst pressure that was ten-fold higher than single-layered tissues but vascular reactivity remained high even though the cells were constricting an additional tissue layer. These results showed that mechanical strength results largely from the biomaterial but contractility requires active cellular machinery. Consequently, they may suggest novel approaches for engineering biomaterials that satisfy the requirement for high mechanical strength while preserving SMC function.