Hydrogels provide the multifunctionality of smart materials and the applicability to medical regulatory systems. Hydrogel membranes that incorporate glucose oxidase for the closed loop treatment of type I diabetes mellitus are characterized and modeled. The Sorensen compartmental model is extended to represent the treatment system of a diabetic patient. The performance of the system closed by a hydrogel-based device is explored and compared to the dynamic behavior of a conventional scheme with an explicit controller element. Anionic and cationic hydrogels are discussed for insulin delivery application. Simulations demonstrate limitations in the range of swelling and contraction of hydrogels in a physiological environment due to the Donnan equilibrium effect. Results show the reduction of peak glucose levels and a basal insulin delivery from a hydrogel membrane system. The evaluation of ionic hydrogel membrane macrosystems prompts the consideration of detected pros and cons using different hydrogels, structures and scales. (C) 2008 American Institute of Chemical Engineers.