Using drugs, machines, and genes to engineer functional muscle

The goal of tissue engineering is to use scaffolding materials and multipotent stem cells to produce tissue replacements. In engineering muscle, this is made more complex by the fact that the function of muscle is to produce force and therefore the scaffold has to be compliant and biodegradable. While great progress has been made towards this goal, a number of obstacles remain, including: 1) vascularization of the engineered muscle; 2) creation of effective interfaces between muscle and bone/artificial materials; 3) maturation of the muscle, since it is developmentally arrested; and 4) the development of normal muscle fibre size and strength. The result is that the current state-of-the-art tissue engineered muscles are 0.2mm thick and produce at best 35% of the relative force of a neonatal muscle. In order to make the engineered muscles bigger and increase their force production, we propose to use drugs to remove inhibitors of muscle growth and development, machines to stretch and electrically stimulate muscle growth and development, and genes to increase muscle fibre size and therefore force production. The research combines discoveries made in vivo studying muscle physiology with our engineered muscle model to try to make bigger, stronger and more adult muscle in culture.