One of the most frequently applied polymers in regenerative medicine is polystyrene (PS), which is commonly used as a flat surface and requires surface modifications for cell culture study. Here, hierarchical composite meshes were fabricated via electrospinning PS with nylon 6 (PA6) to obtain enhanced cell proliferation, development, and integration with nondegradable polymer fibers. The biomimetic approach of designed meshes was verified with a scanning electron microscope (SEM) and MTS assay up to 7 days of cell culture. In particular, adding PA6 nanofibers changes the fibroblast attachment to meshes and their development, which can be observed by cell flattening, filopodia formation, and spreading. The proposed single-step manufacturing of meshes controlled the surface properties and roughness of produced composites, allowing governing cell behavior. Within this study, we show the alternative engineering of nondegradable meshes without post-treatment steps, which can be used in various applications in regenerative medicine. supervision, U.S.; project administration, U.S.; funding acquisition, U.S. All authors have read and agreed to the published version of the manuscript.