Engineering strategies for the construction of oriented and functional skeletal muscle tissues

Abstract The growth and formation of tissues, such as skeletal muscle, involve a complex interplay of spatiotemporal events, including cell migration, orientation, proliferation, and differentiation. With the continuous advancement of in vitro construction techniques, many studies have contributed to skeletal muscle tissue engineering (STME). This review summarizes recent advances in the ordered construction of skeletal muscle tissues, and evaluates the impact of engineering strategies on cell behavior and maturation, including biomaterials, manufacturing methods and training means. Biomaterials are used as scaffolds to provide a good microenvironment for myoblasts, manufacturing methods to guide the alignment of myoblasts through construction techniques, and external stimulation to further promote the myoblast orientation and maturation after construction, resulting in oriented and functional skeletal muscle tissues. Subsequently, we critically examine recent advancements in engineered composite skeletal muscle constructs, with particular emphasis on essential functionalization strategies including skeletal muscle vascularization, innervation and others. Concurrently, we evaluate emerging applications of STME in diverse translational areas such as volumetric muscle loss treatment, muscle-related disease models, drug screening, biohybrid robots, and cultured meat. Finally, future perspectives are proposed to provide guidance for rational design based on engineering strategies in STME.