Electrical stimulation as a biomimicry tool for regulating muscle cell behavior

Abstract

There is a growing need to understand muscle cell behaviors and to engineer muscle tissues to replace defective tissues in the body. Despite a long history of the clinical use of electric fields for muscle tissues in vivo, electrical stimulation (ES) has recently gained significant attention as a powerful tool for regulating muscle cell behaviors in vitro. ES aims to mimic the electrical environment of electroactive muscle cells (e.g., cardiac or skeletal muscle cells) by helping to regulate cell-cell and cell-extracellular matrix (ECM) interactions. As a result, it can be used to enhance the alignment and differentiation of skeletal or cardiac muscle cells and to aid in engineering of functional muscle tissues. Additionally, ES can be used to control and monitor force generation and electrophysiological activity of muscle tissues for bio-actuation and drug-screening applications in a simple, high-throughput, and reproducible manner. In this review paper, we briefly describe the importance of ES in regulating muscle cell behaviors in vitro, as well as the major challenges and prospective potential associated with ES in the context of muscle tissue engineering.

Keywords: Electrical stimulation; alignment; bio-actuators; differentiation; drug-screening models; muscle cells; muscle tissue engineering.

Figure 1. ES of muscle cells on a microgrooved GelMA hydrogel. C2C12 myotubes were immunostained against the myosin heavy chain protein (green). Z-lines within the electrically stimulated myotubes were obvious after ES, indicating highly mature myotubes compared with the non-stimulated myotubes. Reproduced with permission of The Royal Society of Chemistry.

Figure 2. Structural characteristics of a natural jellyfish and its synthetic medusoid counterpart. (A) Body structure of the jellyfish (top) and medusoid (bottom). (B) Schematics of shape and anisotropic muscle tissues in the jellyfish (top) and medusoid (bottom). Here, ES was used to control the movement of the medusoid. (C) Stroke kinematics of the jellyfish (top) and medusoid (bottom). Reproduced from ref. with permission.