Development of a Platform for the Biofabrication of Endocrine Pancreatic Tissue Constructs through Co-Axial Micro-Extrusion

Type-1 Diabetes (T1D) is an auto-immune disease in which the insulin-producing β-cells in the islets of Langerhans are destroyed, affecting over 20 million patients worldwide. Islet transplantation may offer a viable treatment strategy, but transplanted islet lifespan is limited by auto- and allo-immune responses and poor engraftment upon transplantation. Biofabrication of tissue engineered constructs encapsulating islets may offer a viable strategy, as this encapsulation may allow for immune-protection of the islets and circumvent issues associated with engraftment. Here, we describe for the first time a single-step fabrication procedure for tissue constructs incorporating isolated mouse islets with supporting endothelial progenitor cells. A platform for the fabrication of these constructs through co-axial micro-extrusion (Dual Ink Co-axial Bioprinter-1; DICAB-1) was first established, characterised and found to be biocompatible with MS1 and β-TC-6 cell lines (endothelial and beta-cells of murine origin, respectively). Bioprinted islets were found to survive fabrication procedures as well as secrete considerable amounts of insulin, albeit with substantial variability and with sub-optimal glucose responsivity. These results constitute a major step towards the development of a sophisticated platform in which constructs incorporating islets, supporting cells and immune protection can be fabricated in a single-step process.