Nordihydroguaiaretic acid (NDGA), an antioxidant with two functional ortho-catechols from the creosote bush, has been shown to increase the mechanical properties of synthetic collagen fibers, producing biologically based, biocompatible fibers with material properties in uniaxial tensile tests to failure that are comparable to those of native tendon (Koob and Hernandez, Biomaterials 23 (2002) 203; Koob et al., J Biomed Mater Res, 56 (2001) 31; 56 (2001) 40). The NDGA polymerization scheme was applied to gelatin hydrogels to determine whether it could provide a viable approach for producing gelatin based biological materials with advantageous mechanical and thermal properties. NDGA treatment eliminated gelatin solubilization from hydrogels in chaotropic agents and increased the thermal stability of gelatin hydrogels from less than 37 degrees C to over 80 degrees C. NDGA caused a dose dependent increase in the compressive stiffness and fracture load of gels ranging in concentration from 2.5% to 40% gelatin in uniaxial, unconfined compression tests to failure. Maximum fracture load averaged 0.5+/-0.1MPa and the compressive modulus averaged 4.4+/-1.4MPa for all gelatin concentrations, however, the concentration of NDGA that produced maximum strength and stiffness varied inversely with gelatin concentration. The compressive strength and stiffness of 5% gelatin hydrogels treated with NDGA were independent of temperature up to 52 degrees C. These results indicate that NDGA polymerization renders gelatin hydrogels thermally and mechanically stable and thereby potentially useful for surgical procedures that would benefit from biocompatible, stable and mechanically competent gelatin-based biomaterials.