Nerve regeneration with electrical stimulation
Updated: Feb 15, 2022
Peripheral nerve damage is a shared global medical problem, which affects thousands of people every year. Unfortunately, even with significant advances in microsurgical techniques, recovery is often incomplete, contributing to neurological deficits that rarely recover their original functional capacity. This defective recovery is mainly attributed to the progressive decline in the regenerative capacity of neurons and denervated Schwann cells over time and distance. The autograft implant is considered the standard clinical treatment; however, the limited availability of donor tissue and the size incompatibility between the donor and recipient nerves limit the application of this technique. 1
Therapeutic applications that use stem cells represent a significant promise for the regeneration of peripheral nerves. However, due to the difficulty of maintaining the viability and the potential for in vivo differentiation of stem cells, fully functional treatments using these cells still face significant obstacles. 2 3
Another promising strategy for this problem is the electrical stimulation of peripheral nerves, which, according to recent research, improves motor and sensory nerve regeneration in animal models of chronic peripheral nerve damage. Low-frequency electrical stimulation causes the neural cyclic adenosine monophosphate (cAMP) to rise, raising the expression of genes associated with growth. This accelerates the growth of the motor and sensory axons at injury sites, increasing nerve regeneration. 4
Figure 1: The effects of cAMP on promoting gene transcription of genes associated with neuron regeneration. 4
A study performed by Fu et al. in 2019 explored the potential of conductive materials composed of graphene oxide (GO) associated with electrical stimulation for nerve repair. A membrane composed of poly (L-lactic-co-glycolic acid) (PLGA) / GO was prepared and neural stem cells (NSCs) were cultured on this material. According to the results, the PLGA / GO membrane presents good hydrophilicity, mechanical resistance, and protein adsorption. Furthermore, in association with electrical stimulation, the PLGA / GO membrane promotes a significant increase in the differentiation of NSC in neurons and considerable neurite elongation. This study evidenced that electrical stimulation combined with conductive composite materials and stem cells is a promising strategy to be used as a new therapeutic combination to treat nerve injuries since the combination of these two factors, is also able to further promote nerve regeneration. 5
Figure 2: Immunofluorescence staining of neurons derived from NSC differentiation. 5
Zhao et al. (2020) developed a study where a polypyrrole/silk fibroin (PPy/SF) conductive composite scaffold was manufactured by 3D bioprinting and electrospinning. Schwann cells were seeded on these scaffolds and electrically stimulated, demonstrating increased viability, proliferation, and migration. Furthermore, the expression of neurotrophic factors was up-regulated. The results indicated that PPy/SF conductive composite scaffolds with longitudinal orientation may be a new strategy for clinical use as they promote nerve regeneration and functional recovery. 6
1. Du, J. et al. Optimal electrical stimulation boosts stem cell therapy in nerve regeneration. Biomaterials 181, 347–359 (2018).
2. Fu, T. et al. Electrical Muscle Stimulation Accelerates Functional Recovery After Nerve Injury. Neuroscience 426, 179–188 (2020).
3. Zuo, K. J., Gordon, T., Chan, K. M. & Borschel, G. H. Electrical stimulation to enhance peripheral nerve regeneration: Update in molecular investigations and clinical translation. Exp. Neurol. 332, 113397 (2020).
4. Gordon, T. Electrical Stimulation to Enhance Axon Regeneration After Peripheral Nerve Injuries in Animal Models and Humans. Neurotherapeutics 13, 295–310 (2016).
5. Fu, C. et al. Effect of electrical stimulation combined with graphene-oxide-based membranes on neural stem cell proliferation and differentiation. Artif. Cells Nanomed. Biotechnol. 47, 1867–1876 (2019).
6. Zhao, Y. et al. Application of conductive PPy/SF composite scaffold and electrical stimulation for neural tissue engineering. Biomaterials 255, 120164 (2020).