Biomimetic engineered muscle with capacity for vascular integration and functional maturation in vivo

Significance Engineering of highly functional skeletal muscle tissues can provide accurate models of muscle physiology and disease and aid treatment of various muscle disorders. Previous tissue-engineering efforts have fallen short of recreating structural and contractile properties of native muscle in vitro. Here, we describe the creation of biomimetic skeletal muscle tissues with structural, functional, and myogenic properties characteristic of native muscle and contractile stress values that surpass those of neonatal rat muscle. When implanted and real-time imaged in live animals, engineered muscle grafts undergo robust vascularization and perfusion, exhibit continued myogenesis, and show further improvements in intracellular calcium handling and contractile function. This process is significantly enhanced by myogenic predifferentiation and formation of aligned muscle architecture in vitro.