Development of Biomimetic Environments with Appropriate Chemical and Mechanical Cues for Cells in Bioengineered Vascular Grafts

Tissue engineered vascular constructs are promising for next generation vascular substitutes.  Currently, one major challenge facing the field is developing biomimetic environments capable of providing appropriate biochemical and biomechanical signals to cells within bioengineered vascular grafts. Previously, we showed that TGF-β1 that was conjugated within fibrin hydrogels through the action of factor XIII prolonged phosphorylation of Smad2 and enhanced contractility of vascular grafts as compared to soluble growth factor. Vascular contractility increased significantly with the concentration of immobilized TGF-β1 in a biphasic manner. Here we examined the hypothesis that mechanical force could further enhance the function of TGF-b1 decorated vascular grafts. To this end, we developed a high throughput biomechanical plate to investigate the effects of different mechano-stimulation protocols on control or TGF-b1 decorated tissue engineered vascular constructs (TEVs). We found that mechanical stimulation induced circumferential alignment of MSCs, increased the collagen content and the Young’s modulus of TEVs. Notably, pulsation at period of 2s and 5% distention significantly increased vascular reactivity through receptor and non-receptor mediated pathways suggesting increased myogenic function. Interestingly, mechanical stimulation of TGF-β1 conjugated TEVs further increased the vasoreactivity and mechanical properties. These results suggest that the optimal combination of mechanical stimulation and growth factor delivery yields more functional and mechanically robust vascular constructs.