Tennessee Valley Health Authority 1 article published in JoVE Bioengineering Sustained Administration of β-cell Mitogens to Intact Mouse Islets Ex Vivo Using Biodegradable Poly(lactic-co-glycolic acid) Microspheres Raymond C. Pasek1, Taylor E. Kavanaugh2, Craig L. Duvall2, Maureen A. Gannon1,3 1Department of Medicine, Vanderbilt University Medical Center, 2School of Engineering, Vanderbilt University, 3Department of Veterans Affairs, Tennessee Valley Health Authority Here, we present methodology to generate and administer compound of interest-loaded poly(lactic-co-glycolic acid) (PLGA) microspheres to intact mouse islets in culture with subsequent immunofluorescence analysis of β-cell proliferation. This method is suitable for determining the efficacy of candidate β-cell mitogens.