Development of efficient drugs and therapies for the treatment of inflammatory conditions in the intestine is often hampered by the lack of reliable, robust, and high-throughput in vitro and in vivo models. Current models generally fail to recapitulate key aspects of the intestine, resulting in low translatability to the human situation. Here, an immunocompetent 3D perfused intestine-on-a-chip platform was developed and characterized for studying intestinal inflammation. Forty independent polarized 3D perfused epithelial tubular structures were grown from cells of mixed epithelial origin, including enterocytes (Caco-2) and goblet cells (HT29-MTX-E12). Immune cells THP-1 and MUTZ-3, which can be activated, were added to the system and assessed for cytokine release. Intestinal inflammation was mimicked through exposure to tumor necrosis factor-α (TNFα) and interleukin (IL)-1β. The effects were quantified by measuring transepithelial electrical resistance (TEER) and proinflammatory cytokine secretion on the apical and basal sides. Cytokines induced an inflammatory state in the culture, as demonstrated by the impaired barrier function and increased IL-8 secretion. Exposure to the known anti-inflammatory drug TPCA-1 prevented the inflammatory state. The model provides biological modularity for key aspects of intestinal inflammation, making use of well-established cell lines. This allows robust assays that can be tailored in complexity to serve all preclinical stages in the drug discovery and development process.

由于缺乏可靠、稳健和高通量的体外和体内模型，开发用于治疗肠道炎症的有效药物和疗法常常受到阻碍。目前的模型通常无法概括肠道的关键方面，导致对人类情况的可译性低。在这里，开发了一种具有免疫能力的 3D 灌注肠道芯片平台，并对其进行了表征，用于研究肠道炎症。四十个独立的极化 3D 灌注上皮管状结构从混合上皮来源的细胞生长，包括肠细胞 (Caco-2) 和杯状细胞 (HT29-MTX-E12)。将可以被激活的免疫细胞 THP-1 和 MUTZ-3 添加到系统中并评估细胞因子的释放。通过暴露于肿瘤坏死因子-α (TNFα) 和白细胞介素 (IL)-1β 来模拟肠道炎症。通过测量顶侧和基底侧的跨上皮电阻 (TEER) 和促炎细胞因子分泌来量化效果。细胞因子在培养物中诱导炎症状态，如屏障功能受损和 IL-8 分泌增加所证明的那样。接触已知的抗炎药 TPCA-1 可防止炎症状态。该模型利用完善的细胞系，为肠道炎症的关键方面提供了生物学模块化。这使得可以根据复杂性定制的稳健分析服务于药物发现和开发过程中的所有临床前阶段。通过测量顶侧和基底侧的跨上皮电阻 (TEER) 和促炎细胞因子分泌来量化效果。细胞因子在培养物中诱导炎症状态，如屏障功能受损和 IL-8 分泌增加所证明的那样。接触已知的抗炎药 TPCA-1 可防止炎症状态。该模型利用完善的细胞系，为肠道炎症的关键方面提供了生物学模块化。这使得可以根据复杂性定制的稳健分析服务于药物发现和开发过程中的所有临床前阶段。通过测量顶侧和基底侧的跨上皮电阻 (TEER) 和促炎细胞因子分泌来量化效果。细胞因子在培养物中诱导炎症状态，如屏障功能受损和 IL-8 分泌增加所证明的那样。接触已知的抗炎药 TPCA-1 可防止炎症状态。该模型利用完善的细胞系，为肠道炎症的关键方面提供了生物学模块化。这使得可以根据复杂性定制的稳健分析服务于药物发现和开发过程中的所有临床前阶段。正如屏障功能受损和 IL-8 分泌增加所证明的那样。接触已知的抗炎药 TPCA-1 可防止炎症状态。该模型利用完善的细胞系，为肠道炎症的关键方面提供了生物学模块化。这使得可以根据复杂性定制的稳健分析服务于药物发现和开发过程中的所有临床前阶段。正如屏障功能受损和 IL-8 分泌增加所证明的那样。接触已知的抗炎药 TPCA-1 可防止炎症状态。该模型利用完善的细胞系，为肠道炎症的关键方面提供了生物学模块化。这使得可以根据复杂性定制的稳健分析服务于药物发现和开发过程中的所有临床前阶段。