Effect of Heparinization on Promoting Angiogenesis of Decellularized Kidney Scaffolds

In recent years, the native decellularized extracellular matrix (ECM) provides a scaffold for tissues and organs, but also supports organogenesis and tissue remodeling. However, the anti-coagulation properties have always been a challenge in the creation of the ideal three dimensional bioscaffold materials for tissue engineering organ construction. This hurdle is also an inevitable issue that researchers have to face in the revascularization of the decellularized kidney scaffolds (DKSs). This manuscript describes the strategies to accelerate the endothelialization of blood vessels of DKSs based on anticoagulation, compared to previous reports in our research. In this study, we prepared a heparinized decellularized kidney scaffold (Hep-DKSs) by end-point attachment (EPA) technology, then binding the vascular endothelial growth factor (VEGF) with the Hep-DKSs in order to rapidly promote the formation of endothelialization of DKSs. Following, the anticoagulant properties and cytocompatibility of the modified scaffolds were investigated in vitro by means of Toluidine blue staining, Platelet adhesion assay and Co-culture of human umbilical vein endothelial cells (HUVECs). Subsequently, the modified scaffolds were transplantated to intrarenal subcapsular of the recipient rat. Then the transplanted specimens were observed on 1, 3, 7, 14, 21 and 28 days after transplantation. The results in vivo showed that the numbers of neovascularization were higher in the heparin cross-linking VEGF decellularized kidney scaffolds (HEP-VEGF-DKSs) than that of other decellularized renal scaffolds. Taken together, these data suggest that HEP-VEGF-DKSs have a good anticoagulation property and biocompatibility, and can slowly release heparin and VEGF, suggesting its ability of improving neovascularization better and faster and potential use for regeneration of whole decellularized kidney.