Intrahepatic islets transplantation is the current β-cell replacement approach in severe T1D patients. However, it application is limited due to shortage organ donor and islets loss after implant due to peritransplant damage. Herein, there is the need to find new approach for efficiently deliver β-cell to T1D patients. To this aim organ bioengineering provides tools able to replicate ex vivo a microenvironment suitable for islets viability, maturation and physiological function. Thus, here we biofabricate an innovative platform: the bioengineered vascularized islet organ (Bio-VIO), based on the ex vivo integration of immature neonatal porcine islets (NPIs), into a revascularized decellularized neonatal pig lung scaffold (α gal-KO). Decellularized lung scaffold are generated through an adapted protocol of detergent perfusion. HE staining and DNA analysis content confirmed the total loss of pig cells while preserving the lung matrix structure and relevant protein components. Bio-VIOs are engineered repopulating decellularized neonatal pig lung left lobe within the vascular compartment with subject-derived blood outgrowth endothelial cells (BOECs) and the alveolar space with NPIs. After 7 days of dynamic culture in a customized bioreactor, we validated Bio-VIO vascular and endocrine ex vivo compartments cell integration, viability and functionality. Islets (INS+, CHGA+) are successfully engrafted in the alveolar space and surrounded by a dense vascular network (hCD31+). Additionally the vascular compartment function is confirmed by fluorangiography assay. Bio-VIO endocrine function is confirmed by dynamic insulin secretion test. We observed a significant improvement in insulin secretion level compared to batch-matched NPIs cultured in vitro, hampering the idea of how a vascularized ECM is able to promote NPIs’ functional maturation. In conclusion, we engineered a biocompatible device based on clinical relevant endothelial and endocrine cell sources able to harbour a therapeutic dose of insulin producing cells. In the next future we will evaluate in vivo the Bio-VIO performance in relevant preclinical model of diabetes.