Objective: This study aimed to investigate the role of an exogenous Epidermal Growth Factor and a hyaluronic acid-based scaffold on fracture healing in a rat femoral fracture model Methods: Forty-eight male Wistar-Albino rats, each weighing a mean 392 grams (range= 350-450 grams) and aged 8.2 months (6-9 months), were used for this experimental study. All surgical procedures were performed on the left femur by a single surgeon. An open femoral fracture was created in all rats. The animals were randomly divided into one of the four groups: Control (12), EGF (12), HA (12) and Combined (12). In the 4th and sixth weeks, samples were processed and analyzed using biomechanical and histological methods. Results: Fracture healing was significantly improved in the Combined group compared to the control one, EGF and HA groups in all parameters at both experimental time points. At the fourth and sixth weeks after surgery, fracture healing in the EGF and HA groups was significantly increased at histological evaluation compared to controls. In addition, compared with EGF, HA and Control groups, a significant difference in callus tissue was detected in the Combined group at 4 and 6-week time points in biomechanical features. Conclusion: This study has shown that combining local EGF and HA scaffold accelerates bone healing and strengthens the bony callus histologically and biomechanically. Using EGF-HA combined scaffolds may represent a possible future strategy in trauma surgery.