Impact of polycaprolactone, alginate, chitosan and zein nanofiber physical properties on immune cells for safe biomedical applications.

Nanofiber safety, especially immunogenicity, is important for their successful translation to clinical setting. This study provides a comprehensive evaluation of how nanofiber physical properties influence immune cells cultured on them, specifically peripheral blood mononuclear cells (PBMCs). We prepared nanofibers with a wide range of physical properties including various diameters, interfibrillar pore sizes and mat thicknesses, using four main polymers: polycaprolactone, alginate, chitosan, and zein. Our findings show that nanofiber diameters had only a marginal influence on the activity of immune cells, whereas interfibrillar nanofiber pore sizes had a significant effect, and mat thickness proved to have the greatest impact. Cells that penetrated deeper into the thick nanofiber mats ceased to proliferate but did not experience cytotoxicity. Moreover, we discovered that PBMCs penetrating the zein/PVP nanofiber mesh exhibited increased metabolic activity, indicating potential immunogenicity, whereas the other tested non-immunogenic nanofibers reduced it. To best of our knowledge, this study is the first to report on the impact of various nanofiber physical properties on in vitro immune cell behavior, thereby expanding the knowledge in the relatively unexplored field of nanofiber immunological safety. It underscores the need for rigorous preclinical nanofiber assessment and setting new standards for designing nanofiber-based biomedical products.