Swelling compensation of engineered vasculature fabricated by additive manufacturing and sacrifice-based technique using thermoresponsive hydrogel

Abstract

Engineered vasculature is widely employed to maintain the cell viability within in vitro tissues. A variety of fabrication techniques for engineered vasculature have been explored, with combination of additive manufacturing with a sacrifice-based technique being the most common approach. However, the size deformation of vasculature caused by the swelling of sacrificial materials remains unaddressed. In this study, Pluronic F-127 (PF-127), the most widely used sacrificial material, was employed to study the deformation of the vasculature. Then, a thermoresponsive hydrogel comprising poly(N-isopropylacrylamide) (PNIPAM) and gelatin methacrylate (GelMA) was used to induce volume shrinkage at 37°C to compensate for the deformation of vasculature caused by the swelling of a three-dimensional (3D)- printed sacrificial template, and to generate vasculature of a smaller size than that after deformation. Our results showed that the vasculature diameter increased after the sacrificial template was removed, whereas it decreased to the designed diameter after the volume shrinkage. Human umbilical vein endothelial cells (HUVECs) formed an endothelial monolayer in the engineered vasculature. Osteosarcoma cells (OCs) were loaded into a hierarchical vasculature within the thermoresponsive hydrogel to investigate the interaction between HUVECs and OCs. New blood vessel infiltration was observed within the lumen of the engineered vasculature after in vivo subcutaneous implantation for 4 weeks. In addition, engineered vasculature was implanted in a rat ischemia model to further study the function of engineered vasculature for blood vessel infiltration. This study presents a small method aiming to accurately create engineered vasculature by additive manufacturing and a sacrificebased technique.