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.

Controlled oxygen delivery to power tissue regeneration

“…S. elongatus has facilitated oxygenation in cardiac tissues during episodes of ischemic stroke 76 . The application of S. elongatus has been extended to the domain of bioprinting, providing oxygenation for cell constructs under hypoxic conditions 77 .…”

External Electrons Directly Stimulate Escherichia coli for Enhancing Biological Hydrogen Production

“…The work showed an external electric field activates the cell membrane potential and voltage-gated ion channels to promote cell alignment and proliferation. 37 This observation suggests that a potential exists for the electric-field coupling synthesis of biohybrid systems with adhering high-dense cells.…”

The effect of continuous long-term illumination with visible light in different spectral ranges on mammalian cells

“…An exciting concept is to exploit photosynthetic oxygen production by microalgae or cyanobacteria for delivery to the oxygen-consuming cells 18 – 21 . Therefore, cocultures of mammalian cells with photosynthetically active cells are established and investigated; first studies demonstrated both, their great potential and their limitations 22 – 26 . A crucial aspect of the development of a cultivation regime compatible with both cell types is the illumination, which is essential to enable photosynthesis.…”

“…In contrast to the above-mentioned applications, which use light at a very specific wavelength and relatively short incubation times, such a coculture approach rather requires a long-term, continuous light exposure to ensure a continuous oxygen supply. In addition, photosynthetically active microorganisms are adapted to sun light with its broad spectrum and therefore, warm white light is the first choice for this approach 18 , 19 , 22 , 23 , 25 , 26 .…”