Remote Magneto–Thermal Modulation of Reactive Oxygen Species Balance Enhances Tissue Regeneration In Vivo

Abstract

One of the hallmarks of tissue repair is the production of reactive oxygen species (ROS), which modulate processes such as cell proliferation. Although several attempts have been made to manipulate ROS levels to increase tissue repair, the lack of techniques able to remotely manipulate the redox homeostasis with spatio–temporal fashion has hindered its progress. Herein, a new approach for tuning the ROS levels using magnetic nanoparticles (MNPs) that act as nanoheaters when exposed to an alternating magnetic field is presented. Two manganese–iron oxide (MnxFe3−xO4) MNPs (with a low and a high Mn2+ content) are designed and probed for the possibility of modulating the ROS balance by magneto–thermal stimulation in the invertebrate model organism Hydra vulgaris, able to fully regenerate. By evaluating the expression of selected genes involved in the maintenance of ROS homeostasis and proliferation pathways, a biphasic modulation of the ROS levels played by the MNPs is found. While MNPs with a lower Mn2+ content are able to positively modulate the regeneration potential under magnetostimulation, MNPs with a higher Mn2+ content cause a different redox imbalance, negatively affecting the regeneration dynamic. This innovative approach reveals a novel way of manipulating redox homeostasis that can advance in the field of tissue engineering.