Excitability of Skeletal Muscle during Development, Denervation, and Tissue Culture

Abstract

A quantitative understanding of the bulk excitability of skeletal muscle tissues is important for the design of muscle tissue bioreactor systems, implantable muscle stimulators, and other systems where electrical pulses are employed to elicit contractions in muscle tissue both in vitro and in vivo. The purpose of the present study is to systematically compare the excitability of mammalian (rat) skeletal muscle under a range of conditions (including neonatal development, denervation, and chronic in vivo stimulation of denervated muscle) and of self-organized muscle tissue constructs engineered in vitro from both primary cells and cell lines. Excitability is represented by rheobase (R(50), units = V/mm) and chronaxie (C(50), units = microseconds) values, with lower values for each indicating greater excitability. Adult skeletal muscle is the most excitable (R(50) ~ 0.29, C(50) ~ 100); chronically denervated whole muscles (R(50) ~ 2.54, C(50) ~ 690) and muscle engineered in vitro from cell lines (C2C12 + 10T1/2) (R(50) ~ 1.93, C(50) ~ 416) have exceptionally low excitability; muscle engineered in vitro from primary myocytes (R(50) ~ 0.99, C(50) ~ 496) has excitability similar to that of day 14 neonatal rat muscle (R(50) ~ 0.65, C(50) ~ 435); stimulated-denervated muscles retain excellent excitability when chronically electrically stimulated (R(50) ~ 0.40, C(50) ~ 100); and neonatal rat muscle excitability improves during the first 6 weeks of development, steadily approaching that of adult muscle.

Engineered skeletal muscle tissue for soft robotics: fabrication strategies, current applications, and future challenges

“…The end result is the formation of linear muscle construct termed a myooid that has sutures on either and that can facilitate its integration with other devices (Figure (j)) and has dense myotubes in the interior with a layer of fibroblasts on the outside (Figure (k)). Myooids have been engineered from C2C12 and primary rat myoblasts and optimized using a fibrin gel release surface has produced constructs capable of generating 36 kPa of tetanic stress, on par with native skeletal muscle. More advanced myooids have added additional tissue types, integrating self‐organized tendon to connect the muscle portion of the myooid to steel anchor points .…”

Efeito da eletroestimulação no músculo desnervado de animais: revisão sistemática

“…Em contrapartida, a utilização do mesmo protocolo de intervenção proposto por Dow et al (31), porém por um período mais prolongado de tempo, não proporcionou aumento signi icativo da massa muscular. Nesse caso, a divergência é explicada pelo defeito em algumas unidades do dispositivo gerador de EE, elaborado inicialmente por Dennis e Dow (38,39) para uso em menor período de tempo, o qual, neste estudo, apresentou falhas na bateria.…”

Tissue Engineering: Current Strategies and Future Directions

“…The controlled release of neurotrophic factors is one potential approach to promote peripheral nerve regeneration and synapse formation with engineered tissue 123. Direct electrical stimulation has proven useful in muscle regeneration124 and may have broader applicability.…”