3D melatonin nerve scaffold reduces oxidative stress and inflammation and increases autophagy in peripheral nerve regeneration

Abstract

Peripheral nerve defect is a common and severe kind of injury in traumatic accidents. Melatonin can improve peripheral nerve recovery by inhibiting oxidative stress and inflammation after traumatic insults. In addition, it triggers autophagy pathways to increase regenerated nerve proliferation and to reduce apoptosis. In this study, we fabricated a melatonin-controlled-release scaffold to cure long-range nerve defects for the first time. 3D manufacture of melatonin/polycaprolactone nerve guide conduit increased Schwann cell proliferation and neural expression in vitro and promoted functional, electrophysiological and morphological nerve regeneration in vivo. Melatonin nerve guide conduit ameliorated immune milieu by reducing oxidative stress, inflammation and mitochondrial dysfunction. In addition, it activated autophagy to restore ideal microenvironment, to provide energy for nerves and to reduce nerve cell apoptosis, thus facilitating nerve debris clearance and neural proliferation. This innovative scaffold will have huge significance in the nerve engineering.

Electrospinning Multilayered Scaffolds Loaded with Melatonin and Fe3O4 Magnetic Nanoparticles for Peripheral Nerve Regeneration

“…As shown in Figure 1H, almost 80% of MLT released from multilayered scaffold within 7 d, while release of MLT from single‐layer scaffold was only 54% even after 21 d. Following PNI, rapid oxidative stress and inflammatory response may result in worse recovery without effective suppression. [ 8a,21 ] Therefore, timely release of MLT was helpful to inhibit oxidative and inflammatory damage and promote axonal regeneration, which could be achieved by multilayered structure of scaffolds.…”

Protein Kinase C Isozymes and Autophagy during Neurodegenerative Disease Progression

“…The encoded proteins of these genes interact with different signaling pathways and serve a protective role for organisms against several pathological conditions including neurodegeneration [10][11][12][13].…”

Neuromodulation of the Pineal Gland via Electrical Stimulation of Its Sympathetic Innervation Pathway

“…Melatonin's antioxidant, anti-inflammatory, and free-radical scavenging properties may also be harnessed to promote tissue regeneration. When delivered via biomaterials that control its release, melatonin accelerates wound repair (Murali et al, 2016), promotes metabolic activity and proliferative capacity of mesenchymal stem cells (Çetin Altındal et al, 2019;Hu and Li, 2019), and enhances peripheral nerve regeneration (Qian et al, 2018). These actions are exerted through melatonin's regulation of the microenvironment and its antioxidant and anti-inflammatory properties.…”