Photosynthetic Cyanobacteria can Clearly Induce Efficient Muscle Tissue Regeneration of Bioprinted Cell‐Constructs

Abstract Tissue engineering strategies using cell‐laden constructs have shown promising results in the treatment of various types of damaged tissues. However, inadequate oxygen delivery to the macroscale 3D cell‐constructs for regenerating skeletal muscle tissue has remained a multiplex issue owing to the pivotal factors including cell metabolism and several regulatory intercellular pathways that eventually influence various cellular activities and determines cell phenotype. To overcome this issue, a photosynthetic cyanobacterium (Synechococcus elongatus) is employed in a methacrylated gelatin bioink. Furthermore, to effectively induce cell alignment in the bioink, in situ electric field stimulation is used in a bioprinting system to fabricate cell‐laden scaffolds for regenerating skeletal muscle tissue. Owing to the synergistic effects of the bioactive microenvironment that rescues cells from hypoxic conditions and activations of voltage‐gated ion channels, highly aligned, multi‐nucleated myofibers are obtained as well as significant upregulation (7–10‐fold) of myogenic‐related genes compared with conventionally prepared cell‐constructs. In addition, in vivo studies using a mouse volumetric muscle loss model demonstrate considerable restoration of muscle functionality and regeneration.