Objective of the present work was the development of a strategy for the synthesis of semi-interpenetrating networks (semi-IPN) based on chitosan and poly(methacrylamide) under physiological conditions. Free radical polymerization of methacryloylglycylglycine (MAGG) in the presence of chitosan and ethylene glycol dimethacrylate as the crosslinker was performed. Chitosan and poly(MAGG) hydrogels having different composition and amount of crosslinker were prepared. The presence of the two polymeric components in the polymer bulk was confirmed by fourier transform infrared spectroscopy (FTIR); thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) were used to further substantiate the structural feature of the semi-IPN hydrogels. Finally, degradation behavior promoted by lysozyme demonstrated that there was 60%, 68% and 76% of degradation of the semi-IPN hydrogel with 8%, 4% and 2% of crosslinker respectively in 28 days. The preliminary investigations of the prepared materials suggest their suitability for applications in tissue engineering and controlled release of bioactive agents. (C) 2012 Elsevier B.V. All rights reserved.