Introduction

Repair of peripheral nerve injury is currently an important research field in neurosurgery and one that presents many difficulties (White et al., 2015). Surgical repair of peripheral nerve injury is different from the unique conditions required for the regeneration of the central nervous system (Hu et al.,2009). Various researchers have concentrated on different surgical repair procedures to better promote fiber regeneration across the abutment joint, as well as to protect the distal target organs effectively. The main tissue-engineering repair methods for peripheral nerve injury are shown in Table 1.The difficulties of repairing peripheral nerve injury have been reported (Jiang et al., 2006; Gu et al., 2014; Oprych et al.,2016). The three main concerns are (1) the effective and accurate connection of fibers with different characteristics, such as sensory and motor nerves in both distal and proximal ends of the injury site. (2) Whether the proximal end provides enough nerve fibers to innervate the proximal target organ. (3)To keep the motor end plates of distal target organ from destabilizing and minimize muscle atrophy before the regenerating proximal nerve fibers grow into and innervate the target organ. The aim of this review is to summarize the progress in tissue engineering for the peripheral nerve, to help newcomers familiarize themselves with this field and promote the development of the repair of peripheral nerve injury.

An electronic search of the Medline database for literature describing tissue-engineering for repair of peripheral nerve injury from its inception to 2018 was performed using the following conditions: (“peripheral nerve injuries” [MeSH terms] OR (“peripheral” [all fields] AND “nerve” [all fields]AND “injuries” [all fields]) OR “peripheral nerve injuries” [all fields] OR (“peripheral” [all fields] AND “nerve” [all fields]AND “injury” [all fields]) OR “peripheral nerve injury” [all fields]) AND (“tissue engineering” [MeSH terms] OR (“tissue”[all fields] AND “engineering” [all fields]) OR “tissue engineering” [all fields]). The results were further screened by title and abstract to present animals and humans. Non-peripheral nerve injury experiments were excluded.

Overview of Peripheral Nerve Injury

Peripheral nerve injury can be divided into several categories: neuropraxia, axonotmesis, neural mutilation and nerve defect (Al-Majed et al., 2000). The axillary, musculocutaneous, median, radial, ulnar, femoral, sciatic and peroneal nerves and the brachial plexus are all relatively easy to damage. Physical and sensory disorders of the extremities are the main symptoms. Surgical repair, decompression, lysis and functional exercise are important in recovering the function of a peripheral nerve (Sosa et al., 2005). The aim of the treatment is to promote nerve regeneration, maintain muscle mass, enhance muscle strength and promote functional recovery. Conservative treatment is relatively simple, while various types of scaffold materials can be used in surgical treatment (Yang et al., 2011).

Table 1 Summary of current tissue-engineering repair methods for peripheral nerve injuryPLA: Polylactic acid; PCL: polycaprolactone; PGA: polyglycolic acid; PLGA: poly lactic-co-glycolic acid ; PLGA:;NGF: nerve growth factor; BDNF:brain derived neurotrophic factor; GDNF: glial cell line-derived neurotrophic factor; FGF-2: fibroblast growth factor 2; NT-3: neurotrophic factor 3;CNTF: ciliary neurotrophic factor; VEGF: vascular endothelial growth field Categories and types Superiority Shortcomings Repair scheme Experimental model Key result measures Artificial synthetic material Number and morphology of regenerating myelinated fibers,nerve function index, nerve conduction velocity, motor end plate and triceps surae muscle morphology Natural biomaterial PLA, PCL, PGA,and PLGA Accelerate the repair process,guide the migration of Schwann cells, induce the formation of normal nerve structure, have good mechanical properties for repair long nerve defect,and good biocompatibility and biodegradability Polymer monomers cost a lot of time and money, poor elasticity and hardness Peripheral nerve scaffold,tube, and microspheres Peripheral nerve defect and repair model in rat, rabbit,and primates Type I collagen,gelatin, silk fibroin,and tropoelastin Good arrangement and structure,aperture size, promote the release of related factors, providing more nutritional factors and more suitable microenvironment,make the repair process more convenient Poor mechanical properties and waterproof effect,brittle and easy to fracture Same as aboveSame as above Same as above New type degradable material Chitosan, graphene,and alginate Give a relatively stable regeneration microenvironment locally, can be absorbed and degraded gradually, reduce scar formation in repairing spinal cord injury, reduce the inflammatory response and accelerate the migration of endogenous neuroblast Short research timeCellular transplant combined with above method Same as above Same as above Seed cells Schwann cells,embryonic stem cells, neural stem cells, and mesenchymal stem cells Generate growth factors, affect the extracellular matrix, promote the formation of myelin, can be differentiated into multiple histiocytic cells Lost the original activity and microenvironment in vivo Same as aboveSame as above Same as above Growth factors NGF, BDNF, GDNF,NGF-β, FGF-2, NT-3, CNTF, and VEGF Regulate microenvironment,promote sciatic nerve regeneration, neuronal survival, synaptic plasticity and neurogenesis Destroyed under high temperature,high pressure or organic solvents easily Same as aboveSame as above Same as above Peripheral nerve assistive technology Pulsed electromagnetic field, electrical stimulation, and ultrasound Enhance the speed and accuracy of axon regeneration of sensory and motor nerve, promote the functional recovery of the sensory and motor nerves, promote the proliferation of growth factors and seed cells Less research and clinically relevant large data samples Specific deviceSame as above Same as above