The effect of heparinized decellularized scaffolds on angiogenic capability.

The immobilization of heparin, a new and versatile approach to the surface modification of decellularized tissues, has the potential to greatly improve the hemocompatibility of engineered tissue constructs derived from decellularized organs. We report on porcine decellularized liver scaffolds (DLSs) heparinized by the end-point attachment (EPA) technique. The heparinized DLSs (HEP-DLSs) have the ability to bind and slowly release heparin-binding growth factors. We hypothesized that DLS-immobilized heparin acts as an antithrombotic coating reagent and binds vascular endothelial growth factor (VEGF) to induce angiogenesis in the DLSs. Human umbilical vein endothelial cells (HUVECs) seeded on HEP-VEGF-DLSs attached and remained bioactive. Using the chicken chorioallantoic membrane (CAM) assay, we found that the HEP-VEGF-DLSs induced a significant and rapid enhancement of angiogenesis compared with native DLSs. Scaffolds were implanted in the greater omentum of rats and evaluated after 7, 14, 21, and 28 days. There were significant increases in the numbers of blood vessels in the HEP-VEGF-DLSs compared with native DLSs at all time-points. The modified method introduced in this article could overcome obstacles faced by conventional matrices that lack the ability to induce rapid and sufficient vascularization.