Bioprinting of Physiomimetic Human Islet-like Cellular Aggregates-Vascular Platform for Functional Maturation of Beta Cells

Abstract

Pancreatic islets are point-shaped cellular aggregates surrounded by capillary network and extracellular matrix (ECM) and aligned with blood vessels. Recent advances in bioprinting technology have enabled the construction of engineered pancreatic tissue recapitulating unique structural features of the human islets. However, current human pluripotent stem cell-derived islets lack vasculatures and pancreatic tissue-relevant environments, which are key triggers of insulin producing-beta cell maturation. In this study, we fabricated human islet-like cellular aggregates (HICAs)-vascular platform using pancreatic tissue-derived ECM-based peri-islet niche-like (PINE) bioink reinforced with basement membrane proteins to attain functional maturation of beta cells. Stem cell-derived islets encapsulated in the PINE bioink showed increased insulin secretion capacity compared to islets encapsulated in the other ECM-derived bioink, confirming that 3D pancreatic-mimetic microenvironment could support beta cell functions with biochemical cues. We further investigated whether the bioprinted HICAs could assemble into co-printed blood vessel, contacting endothelial cells, via biostructural cues. Bioprinting of HICAs-vascular platform guided not only pancreatic tissue-specific architecture but the mature behavior of beta cells in vitro. Our platform will potentiate the application of the physiomimetic pancreatic tissue model for diabetes research, opening chances for precision therapeutic drug testing and mature tissue transplants.