Human lung organoids (HLOs) are increasingly used to model development and infectious diseases, however their ability to recapitulate functional pulmonary tissue response to nanomaterial (NM) exposures has yet to be demonstrated. Here, we established a lung organoid exposure model that utilises microinjection to present NMs into the lumen of organoids. Our model assures efficient, reproducible and controllable exposure of the apical pulmonary epithelium, emulating real-life human exposure scenario. By comparing the impact of two well studied carbon-based NMs, graphene oxide sheets (GO) and multi-walled carbon nanotubes (MWCNT), we validated lung organoids as tools for predicting pulmonary NM-driven responses. In agreement with established data, we demonstrate that MWCNT, but not GO, elicit adverse effects on lung organoids, leading to a pro-fibrotic phenotype. Our findings reveal the capacity and suitability of HLOs for hazard assessment of NMs, aligned with the much sought-out 3Rs (animal research replacement, reduction, refinement) framework.

中文翻译：

---

功能性人肺类器官模拟碳纳米材料暴露引起的肺组织反应

人肺类器官 (HLO) 越来越多地用于模拟发育和传染病，但其重现功能性肺组织对纳米材料 (NM) 暴露的反应的能力尚未得到证实。在这里，我们建立了一种肺类器官暴露模型，利用显微注射将 NM 呈现到类器官的管腔中。我们的模型可确保心尖肺上皮的有效、可重复和可控暴露，模拟现实生活中的人类暴露场景。通过比较两种经过充分研究的碳基 NM、氧化石墨烯片 (GO) 和多壁碳纳米管 (MWCNT) 的影响，我们验证了肺类器官作为预测肺部 NM 驱动反应的工具。与既定数据一致，我们证明 MWCNT 而不是 GO 对肺类器官产生不利影响，导致促纤维化表型。我们的研究结果揭示了 HLO 对 NM 进行危害评估的能力和适用性，与备受追捧的 3R（动物研究替代、减少、细化）框架保持一致。