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Epithelium and endothelium, occupying a significant proportion of cells in the human body, play a crucial role in maintaining organs’ normal structure and function. Various methods have been employed to study the physiology and pathology of epithelium and endothelium. However, these conventional methods, such as animal trials and two-dimensional (2D) cell culture, fail to precisely simulate the complex biology of the human body due to the species difference and lack of the native microenvironment in human systems, which is essential for cell culture. To overcome these limitations, epithelium/endothelium on chips have been proposed, which can mimic the pathophysiology of native human systems in a controllable way. This review introduces the recent progress in epithelium/endothelium on chips, aiming to provide a comprehensive review of the fabrication and application of this technology. We first depict the chips’ basic components, materials, and fabrication techniques. Then, we focus on different chip types, from single cell-on-chip, single organ/tissue-on-chip, to multi-organs-on-chip. After that, we describe the biomedical applications such as in vitro study of the physiology and interaction of organs, construction of disease models, and drug development. Finally, the recent challenges and future outlook of epithelium/endothelium on chips are discussed.

Liver plays a critical role in drug metabolism and nowadays multi-cellular culture systems aiming at imitating liver-specific morphology and functionality are advancing robustly. Numerous immortalized or stem cell-induced hepatic cell lines have been investigated to enhance the hepatic phenotype in establishing co-culture systems. Owing to the robust progresses of microtechnology and bioengineering, two-dimensional (2D) co-cultures such as sandwich culture and micropatterned co-culture systems have emerged. Controllably arranging the hepatocytes and fibroblasts allows bio-mimic homotypic and heterotypic interactions, and the miniaturized co-culture platform realizes high-throughput and sensitive drug screening. Yet, to address the rapid dedifferentiation and the decreased maintenance of hepatic functions existing in 2D cellular systems, various three-dimensional (3D) and dynamic hepatocyte co-culturing formats have been established to obtain more physiologically relevant liver microsystems and prolonged hepatic functionalities, such as spheroid barcodes, liver organoids, bioengineered hepatic spheroids, and microfluidic perfused liver-on-a-chip. In this review, we first introduce the typical structural color spheroid barcodes which facilitate multiple screening and testing. Then we sketch various advances in liver-imitating cellular co-culture protocols through representative examples. Meanwhile, we summarize current difficulties and propose the prospects of bioengineered liver-on-barcode systems for reliable and high-throughput drug screening.

When organs, especially external organs are injured, pathogens and excessive water loss can threaten the wound healing process and cause local irreversible tissue damage. Here, novel natural κ-Carrageenan microparticles (MPs) able to deliver bioactive proteins and small molecules to the wound surface for promoted regeneration were developed using microfluidic electrospray. The side chains of κ-Carrageenan were modified with methacrylate pendant groups to make the monomer photonic cross-linkable. By changing the concentration of methacrylated-κ-Carrageenan, different porosities of MPs with controllable drug loading were achieved. The size of the MPs can also be tailored by adjusting the voltage of the applied electric field. Vascular endothelial growth factor (VEGF) and antimicrobial peptides Eumenitin were co-loaded into the microparticles (VEGF-Eumenitin-MPs) and released sustainedly in phosphate-buffered saline. The VEGF-Eumenitin-MPs had high biocompatibility and intensive antibacterial activities for bacteria. Furthermore, the antibacterial and angiogenetic properties of the VEGF-Eumenitin-MPs were demonstrated in a infectious wound model and the chronic wound healing process was significantly enhanced in vivo. Therefore, the developed porous MPs with sustained drug release properties have the potential to serve as a platform to deliver bioactive proteins and small molecules to the wound surface for promoted regeneration.