Tissue Engineering and Regenerative Medicine

The pancreatic islets transplantation (ITx) is a therapeutic alternative for patients with type-1 diabetes mellitus suffering from the hypoglycemia unawareness. The current protocol of ITx is limited, among other factors, by a suboptimal engraftment of islets after infusion into the hepatic portal vein. This results immediately in significant reduction of the graft and in unsatisfactory long-term graft viability predominantly due to an insufficient vasculature and supraphysiological nutrients,drugs and toxins concentration within portal vein blood. Therefore, a considerable effort has been spent to bioengineer an extra-hepatic transplant site rich in vasculature network similar to situation in native pancreas. We aimed to create a highlyvascularized bioartificial cavity using a macroporous polylactide-based scaffold with anisotropic channeled pores as a template,and a host body as the bioreactor. The capsular-shaped scaffolds were prepared using the Dip-TIPS method. We evaluated the effect of the scaffold pore architecture, implantation site and introduction of the vascular endothelial growth factor on the scaffold vascularization. In vivo studies (a rat model) showed the ability of the scaffold pore architecture to guide cell infiltration fully in omentum and partially when implanted subcutaneously. The in vivo magnetic resonance imaging data and immuno-histochemical analysis revealed the enhanced vascularization of the VEGF/scaffolds when compared to unmodified ones. The current study is a significant step forward in the field of biomaterial based extra-hepatic site for islets transplantation.