Speaker
Description
Introduction
The main defense mechanism against inhaled airborne particles is the epithelial barrier, consisting of lung epithelial cells connected by adherent junctions. While some airborne particles are eliminated by the innate defense system, those that are not detected, continue to progress in the body. In the long-term and high-concentration exposures the particles may escape the radar of the immune system1 which in turn triggers oxidative stress, inflammation, and apoptosis mechanisms that lead to the disruption of the barrier integrity2. Impairment of homeostatic interaction of cell-level to system-level defense mechanisms increases susceptibility to respiratory diseases and can contribute to disease initiation in other tissues of the human body. Physiological and anatomical mimicry models of the respiratory system have been proven to be essential for drug development and elucidating the pathophysiological-mechanisms of diseases triggered by epigenetics and hereditary genetic factors. Lung epithelial models can be organized as monoculture/multicultural cells with supporting scaffolds such as trans-wells and bio-gels. Notably as a novel study niche, organ-on-a-chips provide controllable physiological conditions that recapitulate tissue specific features. Epithelial cells, endothelial cells, their basement membranes, and interstitial space between these two monolayered cells provide an extracellular matrix of the lung epithelial barrier. The hierarchical structure of extracellular matrix (ECM) can be emulated by two chambers containing a biological or synthetic membrane, which is functionalized with epithelial-endothelial cells. Hydrogel-based systems such as type-I-collagen scaffolds, commercial matrices (Matrigel, gelMA) and decellularized-tissue-derived-scaffolds are also employed for housing cells3. Interestingly, decellularized leaves have been utilized as vasculatures4 or scaffolds5. Thus the choice for fabrication would heavily rely on the specific requirements of the model.
Methods
Polydimethylsiloxane based soft molded organ-on-a-chip platform was designed and fabricated to emulate epithelial barrier micro-physiology for evaluating the effects of aerosol exposure.
Results
Optimized model in terms of flow mechanics and the transport of microplastic particles were numerically modeled using the finite element calculation method. TEER measurements validated the barrier integrity has been successfully achieved in organ-on-a-chip platform while the exposure causes the disturbance of barrier integrity and cell viability demonstrated with IF-stainings.
Discussion
Obtaining a proven and repeatable model for epithelial barriers allows us to investigate the toxicology of pollutants and study new therapeutic breakthroughs for a healthier future. Innovative approaches such as the organ-on-a-chip systems stand out as promising candidates for these models
Acknowledgement: The funding provided by TUBITAK through 123M406 project is highly appreciated.
References
(1) Adami, G.; Pontalti, M.; Cattani, G.; Rossini, M.; Viapiana, O.; Orsolini, G.; Benini, C.; Bertoldo, E.; Fracassi, E.; Gatti, D.; Fassio, A. RMD Open 2022, 8 (1), e002055
(2) Raby, K.L.; Michaeloudes, C.; Tonkin, J.; Chung, K.F.; Bhavsar, P.K. Front.Immunol. 2023, 14, 1201658
(3) Bennet, T.J.; Randhawa, A.; Hua, J.; Cheung, K.C. Cells 2021, 10 (7), 1602
(4) Filiz, Y.; Arslan, Y.; Duran, E.; Saglam-Metiner, P.; Horozoglu, S.; Paradiso, A.; Martinez, D. C.; Sabour-Takanlou, M.; Heljak, M.; Jaroszewicz, J.; Biray-Avci, C.; Swieszkowski, W.; Yesil-Celiktas, O. Appl.Mater.Today 2024, 36, 102015. 102015
(5) Arslan, Y.; Paradiso, A.; Celiktas, N.; Erdogan, T.; Yesil-Celiktas, O.; Swieszkowski, W.Eur.Polym.J. 2023, 198, 112415. 112415
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