In vitro simulation of cellular exercise environments: advancements in methodology and signal simulation

• Existing in vitro exercise simulation techniques can replicate individual signals (e.g., mechanical stretch, electrical stimulation) but fail to capture the complex multi-dimensional interactions of the exercise microenvironment. • Integrating mechanical, electrical, and biochemical signals in a single platform is essential for accurately mimicking exercise-induced cellular adaptations. • Exercise mimetics, conditioned serum, and exosomes offer promising approaches to reproduce systemic exercise effects in vitro. • Multi-organ-on-chip technologies enable the simulation of systemic exercise responses, facilitating research on inter-organ crosstalk and therapeutic interventions.