Growth Factors for Skeletal Muscle Tissue Engineering

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Abstract

Tissue-engineered skeletal muscle holds promise as a source of graft tissue for repair of volumetric muscle loss and as a model system for pharmaceutical testing. To reach this potential, engineered tissues must advance past the neonatal phenotype that characterizes the current state of the art. In this review, we describe native skeletal muscle development and identify important growth factors controlling this process. By comparing in vivo myogenesis to in vitro satellite cell cultures and tissue engineering approaches, several key similarities and differences that may potentially advance tissue-engineered skeletal muscle were identified. In particular, hepatocyte and fibroblast growth factors used to accelerate satellite cell activation and proliferation, followed by addition of insulin-like growth factor as a potent inducer of differentiation, are proven methods for increased myogenesis in engineered muscle. Additionally, we review our recent novel application of dexamethasone (DEX), a glucocorticoid that stimulates myoblast differentiation, in skeletal muscle tissue engineering. Using our established skeletal muscle unit (SMU) fabrication protocol, timing- and dose-dependent effects of DEX were measured. The supplemented SMUs demonstrated advanced sarcomeric structure and significantly increased myotube diameter and myotube fusion compared to untreated controls. Most significantly, these SMUs exhibited a fivefold rise in force production. Thus, we concluded that DEX may serve to improve myogenesis, advance muscle structure, and increase force production in engineered skeletal muscle.

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