Since the prevalence of coronavirus disease 2019 (COVID-19), the neuromuscular complications caused by the virus have emerged visibly. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, could bind to angiotensin-converting enzyme 2 and transmembrane protease serine subtype 2 receptors on nerve cell membranes [1], and infect the peripheral nervous system via axonal transport and trans-synaptic transfer [2]. SARS-CoV-2 infection could cause immune-mediated multiple peripheral nerve injuries, including headache, taste and smell dysfunction, Guillain-Barré syndrome or chronic inflammatory demyelinating polyneuropathy, and secondary neuromuscular complications [3], [4]. PNI is one of the most difficult health challenges currently, accounting for 1.5–4.0% of global trauma cases annually [5]. The consequences of PNI are severe, resulting in substantial economic and social burdens, due to the sacrifice of labor capacity and increasing cost of the treatment [6].

The peripheral nervous system (PNS) is capable of spontaneous regeneration to some extent. PNS glial cells, such as Schwann cells (SCs), tend to redifferentiate themselves into a regenerative phenotype and can initiate the neuronal regenerative process and the regeneration process occurs immediately after injury [7], [8]. At the proximal site of the injured nerve, separated axons and cell bodies degenerate via a programmed cell death pathway [9]. At the distal site, axons and surrounding myelin begin to degrade in 24–48 h after the damage, known as Wallerian degeneration [10]. Then the harmful debris will be removed. SCs phagocytize myelin debris, until only empty endoneurial tubes remain. Following the elimination of the debris, SCs fill the empty endoneurial tubes and arrange into the characteristic Büngner bands, facilitating the rebuilding of axons. Meanwhile, macrophages are recruited to stimulate the proliferation of SCs and the fibroblasts, which are related to the axonal regeneration process [11]. Finally, growth cones arise in the proximal end, following Büngner bands, which is essential for the advancement of the regenerating axon [12].

Nerve autografts and allografts are still the most adaptive options and provide the best chances of recovery in clinical [13], [14]. However, the outcomes of autograft are far from satisfactory because only 25% of patients regain proper motor function and less than 3% recuperate sensation to a full extent [15], quite apart from the intrinsic limitations, such as the mismatched nerve size and donor site morbidity. For severe nerve injuries with long segmental defects, patients have inferior prognosis and functional recovery after surgical treatment, requiring intervention through tissue engineering strategies [16]. Nerve guide conduits (NGCs) are often used for bridging nerve defects. A number of researchers are now focusing on constructing NGCs with better physiological functions through material selection and modification, here we define them as artificial nerve scaffolds (ANSs).

It is of vital importance to mimic the complex anatomical function of the nervous system. Hence, ANSs should possess good biocompatibility and low immunogenic reactions, and be able to facilitate cellular adhesion and growth of damaged nerve tissues in 3D. The components of ANSs should be biodegrade, ideally at the similar rate as nerve regeneration. Besides, ANSs should provide sufficient mechanical properties to prevent their rupture during the patient’s movements and lessen tension in the damaged area. Furthermore, ANSs should have suitable porosities that can inhibit fibroblast migration and prevent the development of scar tissue at the site of injury, but also promote the intercellular communication of SCs and the growth of axons [15], [17].

Therefore, the materials used for ANS need to be biodegradable, such as polyglycolic acid (PGA) [18], polylactic-co-glycolic acid (PLGA) [19], polycaprolactone (PCL) [20], poly (l-lactic acid-co-caprolactone) (PLCL) [21] etc., as well as natural-based biomaterials, including collagen [22], laminin [23], [24], fibrin [25], hyaluronic acid [26], chitosan (CHI) [27], [28]. Some NGCs prepared from these materials have been approved by the Food and Drug Administration (FDA) [29], [30], [31]. Meanwhile, the architecture of the ANS is also important. The lumen of the ANSs can provide free space for aligned neurite outgrowth, and it could also be filled with various topographical and biological cues to provide a supporting structure and microenvironment to accelerate cell ingrowth and guidance [32], [33].

The nervous system has particular electrophysiological properties, so the role of electrical signals cannot be ignored in the repair of nerve damage using ANSs. Endogenous electrical signals play a vital role in the revival of damaged tissue utilizing stem cell induction, modulation of the function of membrane enzyme protein, alteration of ligand-receptor formation, and ion channel conformational changes [6], [34]. Electrical treatment of biological systems or cells can lead to favorable biochemical and physiological responses. Thus, conductive components should be considered. In order to improve the results of injured nerve regeneration.