Mathematical Model for Microencapsulation of Pancreatic Islets within a Biofunctional PEG Hydrogel Seda Kzlel* Introduction Poly(ethylene glycol) diacrylate (PEG-DA) hydrogel mem- branes have been widely used for encapsulation of variety of cell types for tissue engineering and regenerative medicine due to their hydrophilic character and biocom- patibility. [1–3] Further, biofunctional PEG hydrogels that incorporate sophisticated biochemical and mechanical cues have been studied extensively to mimic biochemical aspects of natural extracellular matrix. The semipermeable PEG hydrogel networks allow molecular transport and serve as an immunoprotective barrier to prevent the rejection of transplanted cells by the immune system of the host. [4] Due to these properties, PEG hydrogels are considered excellent materials for encapsulation of pan- creatic islets for the treatment of type 1 diabetes. [5,6] Immunoprotective barrier must be designed to allow the passage of low-molecular-weight nutrients and waste, as well as small proteins (e.g., insulin), while simultaneously preventing contact between host immune cells and encapsulated islets and the diffusion of large antibodies. In addition, recent studies have provided evidence that synthetic peptide epitopes might be useful in the design of an islet encapsulation environment to promote islet survival and function. [6–8] Thickness and permeability of the membrane, as well as the level of peptide incorporation within the membrane, are all critical factors that determine the success of immunoprotective devices and islet survival. These are crucial because a thick membrane can present a Full Paper S. Kızılel Department of Chemical and Biological Engineering, Koc ¸ University, Istanbul, 34450, Turkey Fax: þ90 212 338 1548; E-mail: skizilel@ku.edu.tr The results of a mathematical model for surface-initiated polymerization of biofunctional PEG-based hydrogels to predict gel properties prior to synthesis is reported. The mathematical model developed in this study describes microencapsulation of islets within an insulinotropic peptide (GLP-1) functionalized PEG hydro- gels. Experimental measurements of the thickness and swelling of GLP-1 functiona- lized hydrogel membranes compare well with the model. The model is capable of predicting the crosslink density, thickness, and the level of GLP-1 incorporation within the membrane. This study demonstrates the possibility of modulating the concen- tration of biological cues in highly per- missive and biofunctional PEG hydrogels for optimizing engineered tissue function. 514 Macromol. Theory Simul. 2010, 19, 514–531 ß 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim wileyonlinelibrary.com DOI: 10.1002/mats.201000033