Zidar Anže, Zupančič Špela, Kristl Julijana, Jeras Matjaž
Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Ljubljana, Aškerčeva cesta 7, 1000 Ljubljana, Slovenia.
Department of Clinical Biochemistry, Faculty of Pharmacy, University of Ljubljana, Aškerčeva cesta 7, 1000 Ljubljana, Slovenia.
Int J Biol Macromol. 2024 Dec;282(Pt 3):137029. doi: 10.1016/j.ijbiomac.2024.137029. Epub 2024 Oct 29.
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.
纳米纤维的安全性，尤其是免疫原性，对于其成功转化至临床应用至关重要。本研究全面评估了纳米纤维的物理性质如何影响在其上培养的免疫细胞，特别是外周血单核细胞（PBMCs）。我们使用四种主要聚合物：聚己内酯、海藻酸盐、壳聚糖和玉米醇溶蛋白，制备了具有广泛物理性质的纳米纤维，包括各种直径、纤维间孔径和垫厚度。我们的研究结果表明，纳米纤维直径对免疫细胞活性的影响微乎其微，而纤维间纳米纤维孔径有显著影响，垫厚度的影响最大。深入厚纳米纤维垫的细胞停止增殖，但未出现细胞毒性。此外，我们发现穿透玉米醇溶蛋白/聚乙烯吡咯烷酮纳米纤维网的PBMCs代谢活性增加，表明具有潜在免疫原性，而其他测试的非免疫原性纳米纤维则降低了代谢活性。据我们所知，本研究首次报道了各种纳米纤维物理性质对体外免疫细胞行为的影响，从而扩展了在相对未被探索的纳米纤维免疫安全性领域的知识。它强调了对纳米纤维进行严格临床前评估的必要性，并为设计基于纳米纤维的生物医学产品设定了新的标准。
