3D Bioprinting of Human Islet-like Cellular Aggregates-Vascular Platform for Modeling Diabetes

Abstract

Pancreatic islets have spheroidal microarchitecture, surrounded by vasculatures and extracellular matrix (ECM), and are located along with a large blood vessel. However, current stem cell-based islet models lack the pancreatic tissue-specific microenvironment and vascular features of islets. In this regard, we developed pancreatic tissue-derived ECM-based peri-islet niche-like (PINE) bioink supplemented with basement membrane proteins, which can promote the structural integrity of islets and the functional maturation of β cells by providing biochemical cues. We further investigated whether the co-culture of endothelial cells could enhance insulin secretion capacity of stem cell-derived islets via secreting paracrine factors. Finally, we fabricated human islet-like cellular aggregates-vascular platform using PINE bioink and 3D bioprinting technology to recapitulate each unique tissue architecture (e.g., spheroid and tubular structure) and validated the applicability of this platform for diabetes modeling. The developed platform reflected not only structural characteristics of pancreatic tissue and but also physiomimetic responses from diabetic islets and vessels. Our platform will facilitate developing improved pharmacotherapies for patients, opening chances for precision diabetic medicine.