A reactive oxygen species-responsive hydrogel encapsulated with bone marrow derived stem cells promotes repair and regeneration of spinal cord injury

Spinal cord injury (SCI) is an overwhelming and incurable disabling event accompanied by complicated inflammation-related pathological processes, such as excessive reactive oxygen species (ROS) produced by the infiltrated inflammatory immune cells and released to the extracellular microenvironment, leading to the widespread apoptosis of the neuron cells, glial and oligodendroctyes. In this study, a thioketal-containing and ROS-scavenging hydrogel was prepared for encapsulation of the bone marrow derived mesenchymal stem cells (BMSCs), which promoted the neurogenesis and axon regeneration by scavenging the overproduced ROS and rebuilding a regenerative microenvironment. The hydrogel could effectively encapsulate BMSCs, and played a remarkable neuroprotective role in vivo by reducing the production of endogenous ROS, attenuating ROS-mediated oxidative damage and downregulating the inflammatory cytokines such as interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha), resulting in a reduced cell apoptosis in the spinal cord tissue. The BMSCs-encapsulated ROS-scavenging hydrogel also reduced the scar formation, and improved the neurogenesis of the spinal cord tissue, and thus distinctly enhanced the motor functional recovery of SCI rats. Our work provides a combinational strategy against ROS-mediated oxidative stress, with potential applications not only in SCI, but also in other central nervous system diseases with similar pathological conditions.

Automated summary

In this study, a hydrogel containing thioketal and ROS-scavenging properties was used to encapsulate bone marrow derived mesenchymal stem cells (BMSCs). The hydrogel promoted neurogenesis and axon regeneration by scavenging excessive ROS and creating a regenerative microenvironment. It effectively reduced endogenous ROS production, attenuated ROS-mediated oxidative damage, and downregulated inflammatory cytokines, resulting in decreased cell apoptosis and scar formation, as well as improved motor functional recovery in spinal cord injury (SCI) rats. This strategy could have potential applications in other central nervous system diseases with similar pathological conditions.