Advances in 3D Bioprinting of Functional Skeletal Muscle Constructs: Focus on Preclinical Models and Evaluation Strategies

Skeletal muscle is an important organ system of the human body, which is responsible for maintaining body posture and movement and also plays an essential role in metabolic and endocrine functions. Although skeletal muscle has intrinsic regeneration ability, loss exceeding approximately 20% of the mass or volume of an individual muscle is considered volumetric muscle loss (VML), which requires surgical intervention for repair. Tissue engineered scaffolds prepared using techniques such as electrospinning, hydrogel casting, particulate leaching, freeze-drying, freeze-thawing, and bioprinting are promising for treating VML injuries. In this review, we discuss various extrusion-based bioprinting strategies to fabricate skeletal muscle constructs aimed at treating VML. Further, this review provides a comprehensive overview of various extrusion-based bioprinting techniques to fabricate muscle tissues such as support-based, co-axial, in situ, cryobioprinting, spheroids, and 4D bioprinting. Different bioink systems, their key properties, and similarities with the native extracellular matrix (ECM) are elaborated. In addition, commonly used preclinical models for assessing the efficacy of skeletal muscle constructs, as well as various experimental methods for assessing functional recovery after VML injuries treated with engineered tissue constructs, are discussed. The limitations of current approaches in the successful fabrication of skeletal muscle constructs using bioprinting techniques are highlighted. Finally, the future scope in the development of more efficient experimental tools to assess the in vivo efficacy of bioprinted constructs to treat VML are discussed.