Bioengineered Humanoid-on-Chip Platforms: Tools for Evaluating the Effects of Environmental Exposure on Human Physiological Barriers
Makaleler > Tam Makale · 2025
Yazarlar: Pelin Saglam Metiner, Özlem GÖKSEL, Tuncay GÖKSEL, Omer H. Yilmaz, Esra Erdal, Özlem YEŞİL ÇELİKTAŞ
Thoracic Research and Practice, Uluslararası, Scopus, 2025, cilt 26, ss 1-3
DOI: 10.4274/thoracrespract.2025.s001
Özet
Environmental pollutants; bioaerosols, chemicals and micro/nano-plastics (MNPs) can disrupt the mechano-biological processes of the human body, impairing structural, cellular, and molecular functions.Such disruptions may ultimately contribute to the onset of toxicity-associated pharmacokinetic disorders.1 Traditional in vivo and 2D in vitro models often fall short in accurately mimicking the complexity of human physiological responses to such environmental exposures.In response, recent advances in microfluidic organ-on-a-chip (OoC) platforms, organoid models, and induced pluripotent stem cell (iPSC) technologies have enabled the development of biomimetic, animal-free, and human-relevant in vitro models.These systems increasingly replicate the molecular, structural, and functional characteristics of both healthy 2 and diseased human tissues, providing powerful tools for toxicological, pharmacological, and pathophysiological research.3,4 To further enhance the predictive power of these models, multi-organ integration strategies are gaining attention particularly those emulating organ axis that are functionally and biochemically interconnected.5 Among these, the brain-lung-liver-intestine axis represents a critical multi-organ network that mediates systemic responses to external insults.For example, inhaled airborne pollutants can initiate inflammatory signaling in the lung, which may be translocated via the bloodstream to the liver and brain.6,7 Similarly, orally ingested MNPs or pharmaceuticals undergo metabolism in the intestine and liver, potentially generating bioactive metabolites that affect the central nervous system (CNS).5,8 Such complex inter-organ interactions are essential to understanding the full scope of environmental toxicity and human pathophysiology, yet are poorly captured in isolated organ models.5 Bioengineered humanoid-on-chip systems that incorporate the brain-lung-liver-intestine axis within a single fluidically linked microphysiological platform offer a novel solution.These integrated systems can simulate real-time organ-organ crosstalk under dynamic flow conditions, mimicking human circulatory, absorptive, and barrier functions with high fidelity.5,6,8 For instance, the intestine-on-chip component can model nutrient or xenobiotic absorption, followed by first-pass metabolism in the liver module, 8 systemic immune or endocrine responses via the lung module, 6 and downstream neuroinflammatory