Widespread application of islet transplantation as a cure for type 1 Diabetes Mellitus patients is limited mainly due to the need for life-long immunosuppression associated with serious side effects. Immunoisolation by encapsulation of islets in semi-permeable membranes may overcome this issue as it allows for transplantation potentially obviating the need for immunosuppressive drug therapy. This work focuses on the development and validation of a model of the mass transfer and secretion kinetics of insulin - the major regulator of glucose homeostasis - in a new microwell membrane based encapsulation device for pancreatic islets. Due to the high number and complexity of parameters that determine the effectiveness of the device, the implementation of a reliable numerical model is of critical importance for optimization of the micro-confined bioengineered environment. The simultaneous solution of mass transfer and uptake/production reactions occurring through the polymeric membrane system and within the islets allows detailed description of the spatial distribution profiles of insulin, glucose, and oxygen with the aim to assure an adequate insulin dynamics. The simulation tool, experimentally validated, is used to improve the scaffold geometry with the aim to assure adequate responsiveness and function over time for future clinical implementation of the device. (C) 2019 Institution of Chemical Engineers. Published by Elsevier B.V. All rights reserved.