Organ-on-a-chip (OOC) is now becoming a potential alternative to the classical preclinical animal models, which reconstitutes in vitro the basic function of specific human tissues/organs and dynamically simulates physiological or pathological activities in tissue and organ level. Despite of the much progress achieved so far, there is still an urgent need to explore new biomaterials to construct a reliable and efficient tissue–tissue interface and a general fabrication strategy to expand from single-organ OOC to multi-organ OOC in an easy manner. In this paper, we propose a novel strategy to prepare double-compartment organ-on-a-chip (DC-OOC) using electrospun poly(l-lactic acid)/collagen I (PLLA/Col I) nanofiber membrane as tissue–tissue interface. The unique features of PLLA/Col I nanofiber membrane like excellent biocompatibility, strong affinity to multiple cells, adjustable orientation, controllable thickness and porosity endow the tissue–tissue interface with excellent semi-permeability, appropriate mechanical support, inducible cell orientation, good cell adhesion and proliferation. The integration of 3D printing technology during the fabrication process enables precise size control of the tissue–tissue interface and stable bonding with microfluidic channels. More importantly, our fabrication strategy and OOC configuration makes it easy to extend from DC-OOC to multi-compartment organ-on-a-chip (MC-OOC). To show its possible application, in vitro jaundice disease model is established by constructing blood vessel/skin/liver/lung organ-on-a-chip via MC-OOC. The downward trends of the cell viability after perfusion of bilirubin, the variation in cell sensitivity to bilirubin for different type of cells and recovery of cell viability after blue light therapy prove the feasibility of this jaundice disease model. We believe this general strategy of constructing tissue–tissue interface and multi-organ OOC can be used for many other in vitro physiological and pathological models.

Graphic Abstract

a Schematic illustration on fabrication process of DC-OOC; b construction of blood vessel/skin/liver/lung organ-on-a-chip as in vitro jaundice disease model

中文翻译：

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基于电纺纳米纤维膜的多室器官芯片作为体外黄疸疾病模型

器官芯片（OOC）现在正成为经典临床前动物模型的潜在替代品，它在体外重建特定人体组织/器官的基本功能，并在组织和器官水平上动态模拟生理或病理活动。尽管迄今为止取得了很大进展，但仍然迫切需要探索新的生物材料以构建可靠且高效的组织 - 组织界面以及以简单的方式从单器官 OOC 扩展到多器官 OOC 的通用制造策略. 在本文中，我们提出了一种使用电纺聚（l）制备双室器官芯片（DC-OOC）的新策略。-乳酸）/胶原蛋白 I（PLLA/Col I）纳米纤维膜作为组织-组织界面。PLLA/Col I 纳米纤维膜的独特特性，如优异的生物相容性、对多种细胞的强亲和力、可调节的取向、可控的厚度和孔隙率，赋予组织-组织界面优异的半透性、适当的机械支撑、可诱导的细胞取向、良好的细胞粘附和扩散。在制造过程中集成 3D 打印技术可以精确控制组织-组织界面的尺寸，并与微流体通道稳定结合。更重要的是，我们的制造策略和 OOC 配置可以很容易地从 DC-OOC 扩展到多室器官芯片 (MC-OOC)。为了展示其可能的应用，通过MC-OOC构建血管/皮肤/肝/肺器官芯片，建立体外黄疸病模型。灌注胆红素后细胞活力的下降趋势，不同类型细胞对胆红素敏感性的变化以及蓝光治疗后细胞活力的恢复证明了该黄疸病模型的可行性。我们相信这种构建组织-组织界面和多器官 OOC 的一般策略可用于许多其他体外生理和病理模型。

图形摘要

a DC-OOC制造过程示意图；b构建血管/皮肤/肝/肺器官芯片体外黄疸病模型