# A Review on Microfluidic Platforms Applied to Nerve Regeneration
## 1 Introduction  
According to the World Health Organization, up to 500,000 people suffer spinal cord injuries (SCI) per year worldwide. SCI can cause associated diseases that decrease patients' life quality and even endanger their lives in ways such as chronic pain, deep vein thrombosis and respiratory complications. Depending on the degree of injures, SCI can be classified as complete SCI and incomplete SCI. With complete SCI, the spinal cord is completely severed, which leads to complete loss of function and sensation below the injury parts. Meanwhile, incomplete SCI patients are able to retain some unilateral sensory and motor function although spinal cord is partially damaged. Among all SCI patients, the incomplete SCI patients account for 65% and the complete SCI patients account for 35% [1]. The recovery rate of incomplete SCI patients is higher than complete SCI patients. About 20% to 75% of incomplete SCI patients regain some degree of walking ability and 20% patients restore motor function completely in 1 year post-injury [2]. Only 5% complete SCI patients are able to recover to their pre-injury status, while the remaining 95% patients have to suffer from various physical disabilities including urinary dysfunction and loss of locomotor function. However, incomplete SCI patients are able to restore physical functions through long-term post-healing treatment and rehabilitation because of neuroplasticity. Neuroplasticity has an important theoretical foundation for incomplete SCI treatment; thus, the treatment principle is to reactivate the residual neural circuits to modulate the impaired functions of body. Treatments such as the spinal epidural electrical stimulation is one of the applications based on the neuroplasticity theory, which can effectively improve the lower limbs locomotor functions of incomplete SCI patients. However, these treatments are not available for complete SCI patients due to the lack of residual nerves. Nowadays, thetreatment for complete SCI remains in the laboratory stage instead of clinical applications, and a priority research area of treatment for complete SCI is nerve regeneration. However, traditional methods for in vitro neuron culture cannot sufficiently simulate or provide precisely control of the different neuronal microenvironments. Therefore, it is difficult to study the molecular and cellular mechanisms that differentially affect different parts of neuronal cells using traditional culture methods [3]. Recent developments in microfluidics and related applications to neurobiology have led to a significant advance in neuron culture. Microfluidic platform can realize precise spatio-temporal control of cellular microenvironment [4], allowing neurobiologists to explore a wide variety of neuronal events such as axon elongation [5; 6], local signaling events [7] and interactions with other cells [8]. Microfluidic platform can manipulate nanoliter-scale liquids by using micro-channels ranging in sizes from ten to hundreds of micrometers [9] that enables single cell manipulation. In addition, microfluidic platform can utilize polydimethylsiloxane polymers materials (PDMS) for microfabrication, which has advantages in biocompatibility, gas permeability and surface-bound gradients to achieve microfabrication of complex tissue/organ cells [10; 11]. Furthermore, the environment in microfluidic devices is enclosed, which is similar to the in vivo environment. These airtight, closed, non-convective devices allow for local accumulation of cellular secreted material in contrast to classical open micropore structure. Compared with traditional neuron culture platform, microfluidic-based platform has many advantages such as single neurons manipulation [12], isolation of axons [13; 14], cultured neuron patterning [15] and neurite outgrowth control [16]. The microfluidic platform can be utilized to detect and analyze chemical factors that inhibit nerve axon regeneration, create different in vitro microenvironments and evaluate candidate drugs that promote nerve growth.