Semi-interpenetrated networks were obtained by free radical polymerization/cross-linking of substituted anhydride modified collagen with 2-hydroxyethyl methacrylate (HEMA) in the presence of ammonium persulfate (APS) and N,N,N',N'-tetramethyl ethylene diamine (TEMED). Substituted anhydride modified collagens, porous materials with vinyl groups, have been previously synthesized by reaction of soluble collagen with dimethyl maleic anhydride (DMA) or citraconic anhydride (CTA). The structure and physicochemical properties of the obtained hydrogels were investigated by Fourier transform infrared spectroscopy, scanning electron microscopy (SEM), and water retention studies. Thermal properties of substituted anhydride modified collagen and their corresponding hydrogels have been investigated by differential scanning calorimetry (DSC) in dried and hydrated states. The denaturation temperature (T-d), denaturation enthalpy, and glass transition temperature (T-g) have been determined, and they were found to be dependent on chemical composition, thermal history, and moisture content. The water states (free or bonded) in the hydrated samples were correlated with their swelling degree.