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• Maleic terminated PEG (PEG-MA) was synthesized without use of any catalyst. • Chitosan/PEG-MA hydrogels were fabricated using facile thermal crosslinking method. • In vitro and in vivo results showed complete biocompatibility and accelerated wound closure for hydrogels. The aim of this study was to fabricate a hydrogel based therapy to accelerate full-thickness wound healing process. Hydrogel matrix was composed from of chitosan as backbone and maleic terminated polyethylene glycol (PEG-MA) as crosslinking agent. PEG-MA was synthesized through a reaction of PEG with maleic anhydride. For hydrogel preparation, various PEG-MA/chitosan ratios were assessed to find the optimum ratio. Further improvement on hydrogel properties was achieved by adding TiO 2 nanoparticles to the matrix. PEG-MA synthesis was confirmed using 1H NMR and FTIR. Several characteristics of hydrogels, including swelling ratio, mechanical properties, water contact angle, and in vitro biocompatibility were appraised for both TiO 2 -free hydrogels and TiO 2 loaded hydrogels. Optimum hydrogels were then selected for in vivo analysis. Results indicate that hydrogels have a porous structure with swelling ratio in the range of 240–280%. In vitro estimations also revealed that hydrogels are completely biocompatible, while they could support human fibroblast cell proliferation during tested time (7 days). In vivo biocompatibility and full-thickness wound closure tests proved the biocompatibility of hydrogels in vivo and accelerated wound closure, respectively, in rat models. Overall, our findings indicate that the fabricated hydrogels are good nominates for wound healing applications as they enhance the wound contraction process with improved vascularization. [ABSTRACT FROM AUTHOR]