Effect of an oxygen-generating scaffold on the viability and insulin secretion function of porcine neonatal pancreatic cell clusters.

Abstract

Islet encapsulation techniques have shown limited success in maintaining islet survival and function because encapsulation decreases oxygen supply. In this study, an oxygen-generating scaffold was fabricated to prevent hypoxic cell damage and improve the viability and insulin secretion of islets. We fabricated an oxygen-generating scaffold by mixing calcium peroxide (CaO2 ) with polydimethylsiloxane (PDMS). We evaluated the effects of the oxygen-generating PDMS+CaO2 scaffold on viability, caspase-3 and caspase-7 activity, oxygen consumption rate (OCR), glucose-stimulated insulin secretion (GSIS), hypoxic cell marker expression, and reactive oxygen species (ROS) levels in porcine neonatal pancreatic cell clusters (NPCCs). We also fabricated a microfluidic device that allowed measuring the effects of the oxygen-generating scaffold on viability. Oxygen generation by the PDMS+CaO2 scaffold was sustained for more than 24hours in vitro. NPCCs encapsulated in PDMS+CaO2 showed higher viability than NPCCs in PDMS scaffolds and control NPCCs grown without a scaffold. PDMS+CaO2 -encapsulated NPCCs showed lower caspase-3 and caspase-7 activity, hypoxic cell expression, and ROS levels, and higher OCR and GSIS than those in PDMS or control cells. Using the microfluidic device, we observed that the viability of PDMS+CaO2 -encapsulated NPCCs was higher than that of PDMS-encapsulated NPCCs. NPCCs in PDMS+CaO2 scaffolds show higher viability and insulin secretion than do NPCCs in PDMS scaffolds and control cells. Therefore, this oxygen-generating scaffold has potential for application in future islet transplantation studies.