Magnetic force-based skeletal muscle tissue engineering for in vitro drug testing

Introduction: Skeletal muscle tissue engineering holds great promise for pharmacological studies. In vitro culture systems are available for drug discovery for patients with injured, diseased and age-related muscle. For drug... [ view full abstract ]

Introduction: Skeletal muscle tissue engineering holds great promise for pharmacological studies. In vitro culture systems are available for drug discovery for patients with injured, diseased and age-related muscle. For drug testing, conventional 2D cell culture systems are based on formation of myotubes on tissue culture dishes. However, the 2D cell culture systems have limitations to mimic in vivo skeletal muscle functions mainly due to lacking the architecture of native muscles. One of the most important characteristics of skeletal muscle is contractile force generation ability, and tissue-engineered skeletal muscle constructs should mimic the architecture of native muscles and reproduce contractile force generation. In the present study, we demonstrate an in vitro system for drug testing using tissue-engineered skeletal muscle constructs. Methods: We have developed a fabrication method of functional skeletal muscle tissue constructs by using a magnetic force-based tissue engineering technique, in which myoblasts were labeled with magnetite nanoparticles, and assembled by magnetic field to form a cell-dense and aligned skeletal muscle-like structure. Small-molecular drugs are used as a model drug. Results and Discussion: In response to small-molecular drugs, myotube differentiation of myoblasts were promoted in 2D cell culture. However, the levels of contractile force generation of tissue-engineered skeletal muscle constructs treated with small-molecular drugs were not consistent with those of myotube differentiation in 2D cell culture. On the other hand, there was a high correlation between sarcomere formation as well as contractile activity in two-dimensional cell culture and contractile force generation of tissue-engineered skeletal muscle constructs. These observations indicate that the contractility data is indispensable for in vitro drug screening.