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In today’s world, wound healing is a growing serious problem for clinical institutes. In this study, nanofibrous scaffolds were prepared using polyurethane as a mat scaffold. Also, by immersing curcumin as an antibacterial component another scaffold was fabricated using the electrospinning technique. The obtained scaffolds were characterized by means of scanning electron microscopy, tensile analysis, porosity, and water vapor transmission rate. MTT and DAPI staining were used to prove the biocompatibility and cell attachment of the nanofibers. The curcumin incorporated into the PU scaffold can stop both the Gram-negative and Gram-positive bacteria activities through direct contact with them. Studies showed that the PU/Curcumin scaffold has considerable ability to play a key role in wound healing applications.