Recent Advances in Electrospun Nanofiber Membrane Based Biomimetic Tissue Barriers and Drug Screening Functions

The construction of highly biomimetic in vitro tissue barrier models is essential for new drug development, as it enables accurate evaluation of the permeability efficiency, safety, and pharmacokinetic properties of drug candidates. Animal models have long been regarded as the standard criterion for assessing drug efficacy; however, they pose increasingly severe ethical concerns. Moreover, substantial interspecies differences in transmembrane transporter expression and metabolic pathways contribute to the low rate of successful clinical translation. Traditional 2D cell culture models lack a 3D matrix microenvironment and physiological mechanical signals similar to those in vivo. Consequently, epithelial or endothelial cells are prone to phenotypic alteration. They struggle to assemble structurally intact and functionally mature tight barriers. As a result, drug permeability and toxicity results often deviate markedly from in vivo physiological conditions. In contrast, electrospinning technology offers a promising approach for constructing biomimetic barriers. Electrospun nanofiber membranes closely resemble the fibrous network structure of the natural extracellular matrix and provide several distinct advantages, including precisely controllable pore sizes, large specific surface areas, and readily modifiable functional surfaces. Furthermore, the arrangement and physicochemical properties of the fibers can be precisely tailored to provide cells with inductive cues that mimic the in vivo physiological microenvironment. This review summarizes the design strategies of electrospun nanofiber membranes for the construction of key tissue barriers, including the lung, blood–brain barrier, intestine, kidney, and skin. In addition, it discusses recent advances in the application of these membranes for drug screening. Finally, universal design principles for cross-barrier construction are proposed. Overall, this review aims to support the development of more efficient and reliable in vitro drug-screening platforms.