Molecular and phenotypic responses to mechanical loading in tissue-engineered skeletal muscle

The overriding aim of this thesis was to optimise, scale and utilise an in vitro model of skeletal muscle in order to establish a hypertrophic loading regime of engineered muscle, thereafter, characterising the molecular mechanisms following mechanical load and application of this regime. Mechanical loading of skeletal muscle results in molecular and phenotypic adaptations typified by enhanced muscle size (hypertrophy). However, skeletal muscle loss (atrophy) as a consequence of acute and chronic illness, immobilisation, muscular dystrophies and sarcopenia, leads to severe muscle weakness, inactivity and increased mortality. Mechanical loading is thought to be the primary driver for skeletal muscle hypertrophy, however the extent to which mechanical loading can offset muscle catabolism has not been thoroughly explored. Studies in humans are limited by the need for repeated muscle biopsy sampling, and studies in animals have numerous methodological and ethical limitations. In this investigation, skeletal muscle was tissue engineered utilising the murine cell line C2C12, which bears both structural and functional resemblance to native tissue and benefits from the advantages of conventional in vitro experiments. [Continues.]