Forty million individuals worldwide suffer from type 1 diabetes. This disease is managed by insulin therapy in a vast majority of patients because of the limited accessibility of beta cell replacement therapies (pancreas or islet of Langerhans transplantation). There is an urgent need for the development of a beta cell replacement therapy that will be available to larger numbers of type 1 diabetic patients. The VANGUARD project aims to deliver an Advanced Therapeutic Medicinal Product (ATMP) of high translational potential, with properties of increased functionality and implantability and protection from immune destruction. We 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. The consortium consists of 5 academic institutions with leading scientists in their field, 2 SMEs and 1 NGO with expertise in ethical and social aspects of transplantation. The ATMP delivered upon completion of the project will provide a model for rapid development of a bioartificial pancreas, utilizing “infinite” sources of insulin-producing cells (stem cell-derived, xenogeneic), and available to all type 1 diabetic patients before they develop the devastating chronic complications of the disease.