In vitro reconstruction of an alveolar barrier for modeling normal lung functions and pathological events serve as reproducible, high-throughput pharmaceutical platforms for drug discovery, diagnosis, and regenerative medicine. Despite much effort, the reconstruction of organ-level alveolar barrier functions has failed due to the lack of structural similarity to the natural basement membrane, functionalization with specific ligands for alveolar cell function, the use of primary cells and biodegradability. Here we report a bipolar cultured alveolar-capillary barrier model of human primary cells supported by a basement membrane mimics of fully synthetic bifunctional nanofibers. One-step electrospinning process using a bioresorbable polyester and multifunctional star-shaped polyethylene glycols (sPEG) enables the fabrication of an ultrathin nanofiber mesh with interconnected pores. The nanofiber mesh possessed mechanical stability against cyclic expansion as seen in the lung in vivo. The sPEGs as an additive provide biofunctionality to fibers through the conjugation of peptide to the nanofibers and hydrophilization to prevent unspecific protein adsorption. Biofunctionalized nanofiber meshes facilitated bipolar cultivation of endothelial and epithelial cells with fundamental alveolar functionality and showed higher permeability for molecules compared to microporous films. This nanofiber mesh for a bipolar cultured barrier have the potential to promote growth of an organ-level barrier model for modeling pathological conditions and evaluating drug efficacy, environmental pollutants, and nanotoxicology.

中文翻译：

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双功能培养的人原发性肺泡-毛细血管屏障模型的生物功能化纳米纤维的地下室膜模拟。

用于模拟正常肺功能和病理事件的肺泡屏障的体外重建可作为可重现的高通量药物平台，用于药物发现，诊断和再生医学。尽管付出了很多努力，但由于缺乏与天然基底膜的结构相似性，利用特定配体实现肺泡细胞功能的功能化，原代细胞的使用和可生物降解性，器官级肺泡屏障功能的重建失败了。在这里，我们报告的人原代细胞的双极培养的肺泡-毛细血管屏障模型由完全合成的双功能纳米纤维的基底膜模拟物支持。使用可生物吸收的聚酯和多功能星形聚乙二醇（sPEG）进行的一步静电纺制工艺能够制造具有互连孔的超薄纳米纤维网。如在体内肺中所见，纳米纤维网具有抵抗循环膨胀的机械稳定性。sPEG作为添加剂，通过肽与纳米纤维的缀合和亲水化作用为纤维提供了生物功能，以防止非特异性蛋白质的吸附。与微孔膜相比，生物功能化的纳米纤维网片促进了具有基本肺泡功能的内皮细胞和上皮细胞的双极培养，并显示了更高的分子渗透性。