Biomimetic hydrogels have been developed to fabricate multifunctional microenvironments for cell culture and tissue fabrication. In the current study, different compositions of gelatin (GA) and carboxymethylcellulose (CMC) synthesized via electrostatic interaction. To increase the interaction between these components phenol moieties were substituted on the backbone of GA (GelaPH) and CMC (CMCPH) via carbodiimide-mediated condensation reaction, and then subjected to enzymatic cross-linking in the presence of horseradish peroxidase and calcium peroxide as an electron donor to create a stable hybrid microenvironment for cell encapsulation and tissue engineering. The gelation time and swelling ration, mechanical strength of hydrogels reduced with increasing CMCPH content. On the other hand mechanical propertise like loss modulus (G'), storage modulus (G'') and compression strength increased by the incorpration of CMC. Computational simulation was performed using the finite element method, and the rate of oxygen transfer to the skin, which is a determining factor in wound healing, was investigated to find the optimal concentration of calcium peroxide. Results show that although, samples with higher concentration of CMCPH had lower percentage of cell viability, they had shorten period of healing procedure. Computational study shows that the exitance of calcium peroxide could bring oxygen releasing properties in syntheiszed hydrogels. The hydrogel including 1mg of CaO2 has the highest oxygen releasing proprties in comparison with other hydrogels, however, the formation of oxygen bubbles decreases the mechanical strength of the hydrogel. Thus, the hydrogel with 0.5mg of CaO2 is considerd as the optimum concentration of calcium peroxide in hydrogels . Overall, the results suggest that the optimum hybrid hydrogel can provide a superior biological microenvironment for fibroblasts in three-dimensional skin tissue engineering.