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.