The broader impact/ commercial potential of the Small Business technology Transfer (STTR) project is to develop a bioreactor that may be used for production and expansion of cells for regenerative medicine, tissue engineering, and drug discovery. While significant advances have been made in developing strategies for the culture and differentiation of pluripotent stem cells, there is a critical gap in scaling these processes up to the number of cells required for clinical and research applications. The specific focus of this project is the scale-up of beta islet cells for the treatment of diabetes. Diabetes currently affects 400 million people worldwide leading to 5 million deaths a year. There is currently no cure. A source of transplantable islet cells could alleviate many diabetic complications and restore the quality of life for millions of individuals.This STTR Phase I project proposes to develop and test a novel wicking bioreactor and bioprocess for expansion of human pluripotent-derived beta islet cells. More specifically, this will require focusing on 3 major objectives: i)Optimizing the cellulosic surface of the wicking matrix with chemical and extra cellular matrix additions to ensure attachment and proliferation of the islet cells; ii)optimizing controlled differentiation parameters such as oxygenation levels and feed rates to achieve a 10 fold increase in differentiated cells; and iii) develop a process using physical and biochemical means to remove the differentiated cells from the matrix while maintaining cellular integrity both in terms of viability and phenotype. These studies will serve as proof-of-principle of the proposed bioreactor for tissue engineering and regenerative medicine applications.