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The hydrophobicity of polyurethane fibers is undesired for tissue engineering. In this work, fibers are fabricated by electrospinning and coated with silk fibroin (SF) for biocompatibility and biologically synthesized silver (Ag) nanoparticles (NPs) for antibacterial activity. The scanning electron microscopy revealed the undistorted morphology and the presence of NPs on fibers. The Fourier transform infrared and thermogravimetric analysis show the successful incorporation of SF and Ag NPs. The water contact angle drops from 101.26±0.2° in pristine to 3.1±0.3° in the hydrothermally treated fibers. The moisture regain from 1.87±0.3% to 6.7±0.4% is observed after 24 h. The mineralization shows the hydroxyapatite NPs in all composites. The large zone of inhibition is observed in the composite, with the Ag NPs equal to 11.5±0.04 mm for Staphylococcus aureus and 18.91±0.02 mm for Escherichia coli. The increased proliferation of HEK 293T cells for 6 days of culture on composite scaffolds compared to the pristine scaffolds is achieved. The cell attachment examinations show successful attachment of cells on fibers and nuclear staining analysis shows the highest proliferation in scaffolds with an intermediate concentration of Ag NPs (10%). This strategy presents a novel improvisation for as‐spun PU fibers that can fabricate wound‐healing biomaterials for tissue engineering.