Genipin-crosslinked gelatin-maltodextrin phase-separated hydrogels consisting of gelatin-continuous or bicontinuous microstructures were developed to regulate swelling and release behavior of four fluorescent markers of varying molecular weights [(fluorescein (332 Da) and FITC-dextrans (FD) (4000-250,000 Da)]. Bicontinuous hydrogels showed significantly greater swelling than gelatin-continuous hydrogels under all conditions (at pH 1.5 and 7.4 and three genipin/gelatin crosslinking ratios) (P < 0.05). With both microstructures, fluorescein showed the largest release rate and total release followed by FD 4000 Da, FD 40,000 Da, and FD 250,000 Da (P < 0.05). Marker molecular weight, pH, and crosslink ratio all affected the rate and amount of release. The mode of transport for the solvent and all markers was Fickian or slightly anomalous, with diffusional exponent (n) values ranging from 0.35 to 0.64. These results demonstrated that with the proper combination of crosslink density, solvent pH, and microstructure, hydrogels with a specified swelling behavior may be developed. This, coupled with a marker of appropriate size, can lead to controllable levels and rates of release. (C) 2011 Wiley Periodicals, Inc. J Appl Polym Sci 121: 2662-2673, 2011