Electrical Signature of Engineered Muscle Tissue: multi-frequency impedance analysis of X-MET

The field of skeletal muscle tissue engineering aims to reproduce the structural and functional complexity of native muscle in vitro, providing advanced models for research and medical applications. In this context, a crucial aspect is represented by the dielectric properties, which allow a nondestructive and label-free insight into tissue composition, microstructure, and functional integrity. Here, we investigated for the first time the passive dielectric behavior of the X-MET, an advanced scaffold-free three-dimensional vascularized skeletal muscle construct, assessed through multi-frequency bioimpedance measurements of impedance magnitude (|Z|), dissipation factor (D), and phase angle (θ). Our findings revealed that, compared with native murine muscle, X-MET exhibited a higher impedance magnitude, a broader dissipation factor dispersion, and distinct phase behavior. These variations are indicative of its heterogeneous cellular composition and extracellular matrix content. Our results demonstrated that XMET not only successfully reproduced fundamental biomechanical and functional features of skeletal muscle, but also displayed measurable electrical signatures that could serve as quantitative, non-invasive indicators of tissue organization and maturation. These findings also highlighted the potential of bioimpedance as a valuable tool for monitoring engineered or 3D printed muscle constructs and supported the use of X-MET as a robust in vitro platform for muscle research and translational studies.