Mechanical stimulation improves tissue-engineered human skeletal muscle

Abstract

Human bioartificial muscles (HBAMs) are tissue engineered by suspending muscle cells in collagen/MATRIGEL, casting in a silicone mold containing end attachment sites, and allowing the cells to differentiate for 8 to 16 days. The resulting HBAMs are representative of skeletal muscle in that they contain parallel arrays of postmitotic myofibers; however, they differ in many other morphological characteristics. To engineer improved HBAMs, i.e., more in vivo-like, we developed Mechanical Cell Stimulator (MCS) hardware to apply in vivo-like forces directly to the engineered tissue. A sensitive force transducer attached to the HBAM measured real-time, internally generated, as well as externally applied, forces. The muscle cells generated increasing internal forces during formation which were inhibitable with a cytoskeleton depolymerizer. Repetitive stretch/relaxation for 8 days increased the HBAM elasticity two- to threefold, mean myofiber diameter 12%, and myofiber area percent 40%. This system allows engineering of improved skeletal muscle analogs as well as a nondestructive method to determine passive force and viscoelastic properties of the resulting tissue.

Effect of MicroRNA Modulation on Bioartificial Muscle Function

“…As previously described, 22,23 BAM troughs were made using silicone tubing (Nalgene), split longitudinally with tiny sections of silicone sheets (Nalgene) that were glued to the open ends of the tubing with RTV silicone adhesive (GE). Small stainless steel minutien pins (Fine Science Tools) held Velcro tabs at the ends of the mold to act as attachment sites for the collagen/matrigel construct, and over time, to maintain passive tension.…”

A 3D-printed platform for modular neuromuscular motor units

“…C2C12s differentiated into mature myotubes in the presence of IGF-1, whose use we previously reported to accelerate muscle differentiation in 3D engineered systems in a physiologically relevant manner 3 . We also hypothesized that forcing the tissue to compact and differentiate in this constrained environment would result in greater myotube alignment along the longitudinal axis 2 , as the imposition of this static mechanical cue during muscle development would contribute to improved functionality and force production 30,31 . The design and fabrication of an instructive environment for this cellular system were easily achieved with the use of stereolithographic 3D printing 24,25 .…”

Recent Applications of Polymeric Biomaterials and Stem Cells in Tissue Engineering and Regenerative Medicine

“…89 Creation of an implantable functional muscle tissue that could restore muscle tissue defects may be a possible solution to treating larger wound areas. 91,92 An essential step in engineering a functional skeletal muscle construct is to mimic the structure of native muscle which is comprised of highly oriented myofibers formed from numerous fused mononucleated muscle cells. 93 Because structure and organization of myofibers dictate tissue function, muscle cell 폴리머, 제38권 제2호, 2014년 alignment that permits organized myotube formation is a crucial step in the musculoskeletal myogenesis.…”