Progress in skeletal muscle tissue engineering: advancing from 3D to 4D bioprinting

Skeletal muscles play a pivotal role in facilitating and stabilizing joint movement, retaining body posture, maintaining temperature, and enabling storage and release of nutrients. While most skeletal muscle injuries are benign and can heal via simple home remedial measures, serious muscle injuries due to excessive tension/torsional forces and volumetric muscle loss (VML) caused by trauma or infection often require surgical intervention. Functional free muscle transfer (FFMT) by harvesting healthy muscle tissue and grafting into the damaged site (i.e. autografts) is the current clinical gold standard; however, FFMT is associated with a myriad of limitations including donor site morbidity, infection, and suboptimal tissue regeneration. Skeletal muscle tissue engineering (SMTE) has made giant strides as a promising alternative option for treating VML injuries by developing viable tissue scaffolds that mimic the organized microarchitecture of native tissue, guide myoblast/myotube alignment, and promote skeletal muscle tissue regeneration. In this review, new advancements in the methodology and fabrication of 3D printed/bioprinted scaffolds for skeletal muscle repair and regeneration are discussed. Further, recent studies that employ novel 4D biofabrication approaches using external stimuli (i.e. magnetic field, electric field, temperature, humidity) to guide time-based shape shifting of printed scaffolds towards achieving tissue-mimicking cellular organization and function are highlighted. Finally, current challenges and future perspectives are presented for further development and clinical translation of 4D printed scaffolds for SMTE applications.