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Owing to significant differences across species in liver functions, in vitro human liver models are used for screening the metabolism and toxicity of compounds, modeling diseases, and cell‐based therapies. However, the extracellular matrix (ECM) scaffold used for such models often does not mimic either the complex composition or the nanofibrous topography of native liver ECM. Thus, here novel methods are developed to electrospin decellularized porcine liver ECM (PLECM) and collagen I into nano‐ and microfibers (≈200–1000 nm) without synthetic polymer blends. Primary human hepatocytes (PHHs) on nanofibers in monoculture or in coculture with nonparenchymal cells (3T3‐J2 embryonic fibroblasts or primary human liver endothelial cells) display higher albumin secretion, urea synthesis, and cytochrome‐P450 1A2, 2A6, 2C9, and 3A4 enzyme activities than on conventionally adsorbed ECM controls. PHH functions are highest on the collagen/PLECM blended nanofibers (up to 34‐fold higher CYP3A4 activity relative to adsorbed ECM) for nearly 7 weeks in the presence of the fibroblasts. In conclusion, it is shown for the first time that ECM composition and topography synergize to enhance and stabilize PHH functions for several weeks in vitro. The nanofiber platform can prove useful for the above applications and to elucidate cell‐ECM interactions in the human liver.

 

Electrospinning has emerged as a versatile and accessible technology for fabricating polymer fibers, particularly for biological applications. Natural polymers or biopolymers (including synthetically derivatized natural polymers) represent a promising alternative to synthetic polymers, as materials for electrospinning. Many biopolymers are obtained from abundant renewable sources, are biodegradable, and possess inherent biological functions. This review surveys recent literature reporting new fibers produced from emerging biopolymers, highlighting recent developments in the use of sulfated polymers (including carrageenans and glycosaminoglycans), tannin derivatives (condensed and hydrolyzed tannins, tannic acid), modified collagen, and extracellular matrix extracts. The proposed advantages of these biopolymer‐based fibers, focusing on their biomedical applications, are also discussed to highlight the use of new and emerging biopolymers (or new modifications to well‐established ones) to enhance or achieve new properties for electrospun fiber materials.

 

Drug-induced liver injury (DILI) remains a leading cause of drug attrition and acute liver failures, partly due to the inadequacy of animal models to accurately predict human clinical outcomes, which necessitates the utilization of in vitro models of the human liver. However, primary human hepatocytes (PHHs) are in short supply for routine drug screening. In contrast, induced pluripotent stem cells (iPSCs)-derived hepatocyte-like cells (HLCs) are a nearly unlimited cell source but display a fetal-like (versus adult-like) phenotype when differentiated using conventional protocols on tissue culture plastic or glass adsorbed with 2D extracellular matrix (ECM) proteins. Electrospinning can produce porous nanoscale 3D fibers that have a large surface area and present a high density of receptor ligands to modulate cell phenotype. However, the application of electrospinning to generate 3D liver-derived ECM substrates for HLC differentiation remains unexplored. Therefore, here we developed methods to a) electrospin nanofibers of different porosities and diameters using porcine liver ECM (PLECM) with or without type I collagen and b) use these fibers to determine functional modulation in iPSC-derived HLCs while using PHHs as a control cell type relative to conventional adsorbed ECM substrates.