A novel dual organ-on-chip platform for prolonged study of lung-muscle crosstalk

Le résumé fourni par la source

Pulmonary and skeletal muscle dysfunction often coincide in COPD, which may be a consequence of inter-organ crosstalk. Lung-derived factors may contribute to muscle deterioration, while muscle-derived myokines may influence lung homeostasis. Traditional static in vitro models fail to mimic inter-organ signaling dynamics. To address this, we developed a dual Lung/Muscle-on-Chip (L/MoC) platform to model lung-muscle interactions under controlled microfluidic conditions. The LMOC consists of microfluidic chips fabricated by sandwiching a laser-cut 500 µm polyester channel-containing layer between two polystyrene substrates, bonded with mild solvents. For the MoC, immortalized human myoblasts were used and for the LoC A549 lung epithelial cells. A ‘universal medium’ was selected out of 8 candidate media based on compatibility for culturing differentiated human myotubes and A549 cells. To enhance fluid management, we developed FlexiX, a novel fluid-controlling hub for sterile medium handling, volumetric adjustments, sampling, and waste disposal. A peristaltic pump maintained a closed fluid circuit at 1 μl/min, where FLexiX switched the circulation from growth to differentiation media into the MoC for 1 and 4 days, respectively. Once myotubes formed, the LoC was integrated into the circuit and muscle differentiation medium was replaced with universal medium. Brightfield microscopy confirmed that our LMoC platform maintained lung and muscle cell viability for up to 10 days—outperforming the 2-day viability of static A549 cultures. By enabling long-term co-culture with dynamic perfusion, our system serves as a robust tool for mechanistic studies and drug testing in lung-muscle crosstalk research.

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