It is urgently necessitate to develop a construct with desirable mechanical properties and antibacterial activity for biomedical applications. Zinc oxide (ZnO) has emerged as a promising antibacterial inorganic agent for the improvement of biopolymer scaffold properties. However, its agglomeration/aggregation has an adverse effect on its performance. In the present work, clay platelets have served as a substrate for decoration of high density, well‐distributed ZnO nanorods via in‐situ synthesis. Then, polycaprolactone (PCL) nanofibers containing 1%, 2%, 4%, and 6% ZnO nanorods decorated on clay platelets (Clay@ ZnO) are fabricated using the electrospinning technique. The tensile strength and modulus of the PCL scaffold are significantly enhanced by increasing Clay@ ZnO content, thanks to the presence of well‐distributed ZnO rods on exfoliated clay platelets. However, the maximum elongation at break is observed for PCL/1% (Clay@ ZnO). Disc diffusion method reveals that good coverage of clay platelets with ZnO nanorods boosts the antibacterial performance of ZnO against both Staphylococcus aureus and Escherichia coli bacteria strains. Moreover, incorporation of Clay@ ZnO powders into the PCL scaffold considerably enhances its antibacterial activity. Cell culturing assay demonstrates the favorable cytocompatibility of prepared nanocomposite nanofibers by promoting cell attachment and proliferation. Such engineered nanocomposite has a high potential to utilize in biomedical applications.
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