Use of Flow, Electrical, and Mechanical Stimulation to Promote Engineering of Striated Muscles

Abstract

The field of tissue engineering involves design of high-fidelity tissue substitutes for predictive experimental assays in vitro and cell-based regenerative therapies in vivo. Design of striated muscle tissues, such as cardiac and skeletal muscle, has been particularly challenging due to a high metabolic demand and complex cellular organization and electromechanical function of the native tissues. Successful engineering of highly functional striated muscles may thus require creation of biomimetic culture conditions involving medium perfusion, electrical and mechanical stimulation. When optimized, these external cues are expected to synergistically and dynamically activate important intracellular signaling pathways leading to accelerated muscle growth and development. This review will discuss the use of different types of tissue culture bioreactors aimed at providing conditions for enhanced structural and functional maturation of engineered striated muscles.

Optogenetic skeletal muscle-powered adaptive biological machines

“…These data serve to demonstrate that mechanically and optically stimulated exercise can lead to significant improvements in muscle functional performance, and the combination of both types of stimuli synergistically enhances force output even further. This result is consistent with previous demonstrations of mechanical and electrical multimodal stimulation for engineered muscle (24,25) but is the first demonstration, to our knowledge, of optical conditioning driving functional improvements in muscle performance. As optical stimulation provides a less invasive and cell type-specific approach for localized control of muscle contraction, this approach to enhancing functional performance is a significant improvement over the current state of the art.…”

A novel bioreactor for the generation of highly aligned 3D skeletal muscle-like constructs through orientation of fibrin via application of static strain

“…Thus, scientists still seek feasible strategies to obtain mature, long, functional muscle fibers in volumetric constructs, with proper vascularization and innervation of the tissue. Proposed approaches to engineer muscle (-like) tissue range from scaffold anchoring [10,40,58] or micropatterning of biomaterials for guided myotube formation [39,60,61] to electrical [36][37][38][39]62] or mechanical stimulation in bioreactors in 2D [29,31,[63][64][65] and 3D settings [6,9,11,14,27,[66][67][68]. However, while there is a clear consensus in the field concerning the necessity for mechanical stimulation in 3D skeletal muscle tissue engineering, not all available systems offer programmable and individually adjustable control over strain parameters.…”

Endothelial Network Formation Within Human Tissue-Engineered Skeletal Muscle

“…In addition, subjecting BAMs to electrical and/ or mechanical stimulation has been described to further improve several muscle characteristics, such as viscoelastic properties, protein synthesis, myofiber diameter, and density, thus improving the level of maturation of myofibers. 32,33 Next to HUVECs, other endothelial cell populations may be worthwhile for further investigation. In particular, endothelial colony-forming cells (ECFCs), also termed blood outgrowth endothelial cells, are able to perform de novo tube formation and are proangiogenic in vitro and in vivo.…”