A regenerative rehabilitation strategy based on rGO scaffolds and treadmill training boosts neural, vascular and muscle repair features in chronic hemisected rats

Recent efforts are providing a better understanding of the complexity of spinal cord injury (SCI), with solid steps towards the cure. In paraplegic patients, motor rehabilitation is well known as the only effective treatment to permanently regain certain degree of functionality. However, few attempts exist to integrate it into other therapeutic strategies such as biomaterials. Herein, we present a novel strategy to enhance neural reparative outcomes of rGO scaffolds by the synergistic application of treadmill training following principles of regenerative rehabilitation. Results prove that this combinatorial therapy boosts regenerative features at the spinal cord and its vasculature, with evident synergistic actions in inflammation (reduction in vimentin and ED-1) and vascularization (increase in RECA-1 and reduction in laminin). At limb muscles, it minimizes the initial loss of oxidative fibers resulting from SCI and augments microstructural features such as the density of muscle fibers and mitochondria and sarcomeres size. It also proved to recover total body weight at the subacute phase and increase the heart and spleen relative weights and revert that of liver at chronic stages. These findings contribute to strengthen the relevance of multifactorial therapies for regenerative medicine in the injured spinal cord.