Coupling biophysical stimuli with functional scaffolds to overcome the current limitations of peripheral nerve regeneration: a review

Peripheral nerve injuries are common occurrences that can lead to the loss of sensibility and function, strongly impairing the patient's quality of life. The current techniques acting on nervous tissue regeneration rely on grafts, which are autologous or synthetic nerve guidance conduits produced by tissue engineering methods. However, even using these procedures, functional recovery is limited to a success rate of around 50%, which indicates the need for improvement in the peripheral nerve regeneration approach. Scaffolds with biomimetic characteristics and functional properties are increasingly being developed based on nanotechnology principles. Moreover, different external biophysical stimuli can be applied to achieve even better results. This review discusses the limiting factors that preclude complete nerve recovery and addresses four biophysical strategies to improve regeneration: electric, magnetic, light, and ion-release-based stimulations. The literature has shown that combining these techniques with nanomaterial-based nerve guidance conduits yields an improved nerve repair process. Furthermore, understanding the biological mechanisms underlying regenerative principles of nerve repair can drive new strategies of nerve tissue engineering under biophysical stimuli, overcoming current limitations of peripheral nerve regeneration.