Fuglsang-Madsen Albert, Haagensen Janus Anders Juul, De Rudder Charlotte, Simões Filipa Bica, Molin Søren, Johansen Helle Krogh
Department of Clinical Microbiology, Rigshospitalet, Copenhagen, Denmark.
The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kgs, Lyngby, Denmark.
Adv Exp Med Biol. 2025;1476:69-85. doi: 10.1007/5584_2024_829.
Despite advances in healthcare, bacterial pathogens remain a severe global health threat, exacerbated by rising antibiotic resistance. Lower respiratory tract infections, with their high death toll, are of particular concern. Accurately replicating host-pathogen interactions in laboratory models is crucial for understanding these diseases and evaluating new therapies. In this communication, we briefly present existing in vivo models for cystic fibrosis and their limitations in replicating human respiratory infections. We then present a novel, 3D-printed, cytocompatible microfluidic lung-on-a-chip device, designed to simulate the human lung environment, and with possible use in recapitulating general infectious diseases.Our device enables the colonisation of fully differentiated lung epithelia at an air-liquid interface with Pseudomonas aeruginosa, a key pathogen in many severe infections. By incorporating dynamic flow, we replicate the clearance of bacterial toxins and planktonic cells, simulating both acute and chronic infections. This platform supports real-time monitoring of therapeutic interventions, mimics repeated drug administrations as in clinical settings, and facilitates the analysis of colony-forming units and cytokine secretion over time. Our findings indicate that this lung-on-a-chip device has significant potential for advancing infectious disease research, in optimizing treatment strategies against infections and in developing novel treatments.
尽管医疗保健取得了进展，但细菌病原体仍然是全球严重的健康威胁，抗生素耐药性的上升使这一威胁更加严重。下呼吸道感染导致的死亡人数众多，尤其令人担忧。在实验室模型中准确复制宿主与病原体的相互作用对于理解这些疾病和评估新疗法至关重要。在本通讯中，我们简要介绍了现有的囊性纤维化体内模型及其在复制人类呼吸道感染方面的局限性。然后，我们展示了一种新型的、3D打印的、具有细胞相容性的微流控肺芯片装置，该装置旨在模拟人类肺部环境，并可能用于概括一般传染病。我们的装置能够使完全分化的肺上皮细胞在气液界面处被铜绿假单胞菌定殖，铜绿假单胞菌是许多严重感染中的关键病原体。通过引入动态流动，我们复制了细菌毒素和浮游细胞的清除过程，模拟了急性和慢性感染。该平台支持对治疗干预进行实时监测，模拟临床环境中的重复给药，并便于分析随时间变化的菌落形成单位和细胞因子分泌。我们的研究结果表明，这种肺芯片装置在推进传染病研究、优化抗感染治疗策略和开发新疗法方面具有巨大潜力。
