Cellular Self-Assembly with Microsphere Incorporation for Growth Factor Delivery Within Engineered Vascular Tissue...

Cellular self-assembly has been used to generate living tissue constructs as an alternative to seeding cells on or within exogenous scaffold materials. However, high cell and extracellular matrix density in self-assembled constructs may impede diffusion of growth factors during engineered tissue culture. In the present study, we assessed the feasibility of incorporating gelatin microspheres within vascular tissue rings during cellular self-assembly to achieve growth factor delivery. To assess microsphere incorporation and distribution within vascular tissue rings, gelatin microspheres were mixed with a suspension of human smooth muscle cells (SMCs) at 0, 0.2, or 0.6 mg per million cells and seeded into agarose wells to form self-assembled cell rings. Microspheres were distributed throughout the rings and were mostly degraded within 14 days in culture. Rings with microspheres were cultured in both SMC growth medium and differentiation medium, with no adverse effects on ring structure or mechanical properties. Incorporated gelatin microspheres loaded with transforming growth factor beta 1 stimulated smooth muscle contractile protein expression in tissue rings. These findings demonstrate that microsphere incorporation can be used as a delivery vehicle for growth factors within self-assembled vascular tissues.