Load-programmable training platform for load-response characterization of engineered skeletal muscle tissue.

Abstract

Engineered skeletal muscle tissues are increasingly used as<i>in vitro</i>models for studying muscle physiology, drug responses, and biohybrid systems. However, many existing models operate under isometric conditions and lack the ability to dynamically control mechanical loading during contraction. In this study, we developed a load-programmable training platform that enables dynamic regulation of mechanical load applied to engineered human skeletal muscle tissues. The system integrates electromagnetic actuation, a displacement sensor, and a closed-loop feedback controller to achieve non-contact load modulation during electrically induced contractions. This configuration enables isotonic contraction under precisely controlled loading conditions. Using the platform, engineered skeletal muscle tissues were subjected to programmable training loads ranging from 0.5 to 0.9 mN. Contractile displacement and metabolic activity were evaluated after a three-day training protocol. Tissues trained under moderate loads exhibited enhanced contractility and increased metabolic activity compared with non-trained tissues, indicating load-dependent functional maturation. Excessive loading reduced contractile performance, suggesting the presence of an optimal loading range. The platform also enabled pharmacological evaluation under controlled mechanical environments. Dose-dependent inhibitory effects of doxorubicin and contractility-enhancing effects of isoproterenol were successfully quantified. Furthermore, cumulative exposure experiments revealed that mechanical loading modulates pharmacological responses. These results demonstrate that the proposed platform provides a versatile<i>in vitro</i>system for studying load-dependent muscle physiology, maturation, and drug responses in engineered skeletal muscle tissues.