Enhancing angiogenesis alleviates hypoxia and improves engraftment of enteric cells in polycaprolactone scaffolds

We examined whether expediting angiogenesis in porous polycaprolactone (PCL) scaffolds could reduce hypoxia and consequently improve the survival of transplanted enteric cells. To accelerate angiogenesis, we delivered vascular endothelial growth factor (VEGF) using PCL scaffolds with surface crosslinked heparin. The fabrication and characterization of scaffolds has been reported in our previous study. Enteric cells, isolated from intestinal tissue of neonatal mice and expanded in vitro for 10 days, exhibited high expression levels for contractile protein α-smooth muscle actin and desmin. The cultured enteric cells were seeded in scaffolds and were implanted subcutaneously in immunodeficient mice for 7 and 14 days. At day 7, the heparin-modified PCL scaffolds with VEGF exhibited significantly increased angiogenesis and engraftment of enteric cells, with a simultaneous reduction in hypoxia. At day 14, the blood vessels grew across the entire thickness of the scaffold and resulted in a significantly diminished hypoxic environment; however, the transplanted cell density did not increase further. In conclusion, the enhancement of angiogenesis reduced cellular hypoxia and improved the engraftment of enteric cells.