VANGUARD will construct a bioartificial pancreas by assembling insulin- producing organoids, composed of islet cells, human amniotic epithelial cells (hAEC) and blood outgrowth endothelial cells (BOECs), into an amniotic membrane-derived hydrogel. Components of the amniotic membrane will provide extracellular matrix and mechanical protection and confer their well-defined anti-inflammatory and immunomodulatory properties to the constructs. hAECs will be genome-edited to overexpress and locally release immunomodulatory molecules (HLA-G, HLA-E, CD47 and PD-L1) and endothelial cells will enhance graft revascularization. Functionality, biocompatibility, potency and safety of the bioartificial pancreas will be assessed in vitro and in vivo by implantation in mice reconstituted with a human immune system as pre-clinical model.