# A Review on Microfluidic Platforms Applied to Nerve Regeneration
## 3 Microfluidic Platforms Applied to Nerve Repair and Outgrowth
### Nerve Repair
#### 3.1.2 Microfluidic Platforms for Different Injury Models  
It is very important to choose suitable injury models for different studies purposes. The regeneration of neurite axon in vitro and depends not only on the experimental method but also on the injury model of nerve cells. Since the level and type of neural injury affect the effectiveness of different repair and assessment of the strategies. The common injury models for study are biochemical injuries (hemolytic injury, excitotoxic injury, immunotoxic injury), physical injuries (stretch injury, compression injury, incision injury), laser-based injuries and vacuum-assisted injuries. Table 3 lists some studies according to the damage mechanism and repair method  
Physical injury is the most commonly used injury model for in vitro nerve regeneration and the leading cause of SCI and CNS disorder. Physical injury to nerve axons includes stretch injury, compression injury, and incision injury. Although there are many methods to reproduce tensile/strain injury in organ-type slices such as [PERSON] [67] and [PERSON] [68]. However, limited by reproducibility, these methods cannot be applied to tensile injuries to single isolated axon. Microfluidic platforms can allow precise delivery of stress/strain-based physical injury to isolated axons, diffuse portions of axons, or axons of different lengths. [PERSON] [69] designed a microfluidic device to apply aerodynamic strain  
Figure 4: Microfluidic platforms for nerve repair. **(A)** Vacuum-assisted axotomy device by [PERSON] **(B)** The schematic diagram of microfluidic device presented by [PERSON] for neuronal compartmentalized injury and regeneration research. The fluidic layer has a micron-scale fluidic network (left part) and contains four parallel cell culture chambers. Two chambers in the middle are used for neuronal culture and are connected by an optimized microslot structure. Two external chambers are connected to the neuronal culture chamber using eight parallel microchannels that are designed for glial cell culture. **(C)** The schematics of axotomy microfluidic device designed by [PERSON] The microchannels for placing neural axon are intersected by an axotomy channel. based damage to axons grown within micro-channels. This design facilitates subsequent microscopic observation of injured axons to examine the dynamics of axonal degeneration and regeneration. [PERSON] [70] designed a microfluidic device to induce strain injury to isolated rat cortical axons. Unlike [PERSON]'s strain injury device, this device can cause smooth localized tensile damage to axons. It caused more than 2 mm of damage to axons and more than 90 um of local tensile damage to axons, including 0.5% of strain or 5% of strain. [PERSON] [71] designed a microfluidic device that reproduces the 3D alignment of axons in CNS and performs precise 3D transection of nerve axons. The device can reproduce mechanical damage to axons by puncturing the neuron-containing Matrigel with a pin. In the research of [PERSON] [64], a pneumatic compression based microfluidic device was developed to generate accurate injury on a single axon. Finite element modelling is utilized to parameterize and normalize the degree of axonal damage by estimating the forces between the injury pad and glass substrate and quantitively characterizing the performance of device. This device enables different levels of deformation of single axon from minor injury to major injury. For example, minor injury (<55 kPa) allows the vast majority of axons to remain health and able to continue to grow. Moderate injury (55-90 kPa) causes the degeneration of majority of axons, with axonal swelling. Major injury (>95 kPa) causes rapid and complete transection of all axons. The vacuum-assisted injury model is one of the common models used to study neuronal injury and regeneration, allowing for precise damage to single neurons. [PERSON] [13] developed the first generation of vacuum-assisted neural injury microfluidic device.