# A Review on Microfluidic Platforms Applied to Nerve Regeneration
## 3 Microfluidic Platforms Applied to Nerve Repair and Outgrowth
### Nerve Repair
#### 3.1.1 Microfluidic Platforms for Different Repairing Methods  
There are basically three methods for regeneration of nerve cells after injury: drug-directed regeneration, NGF-directed regeneration and elimination of factors that inhibit axonal regeneration to induce regeneration. Some experimental protocols use a combination of those methods; thus, the microfluidic device has to be changed and adapt to these protocols.  
[PERSON] [63] designed a vacuum-assisted axotomy microfluidic device for studying the effect of neuromuscular activities on axonal repair after axotomy. NFGs such as brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF) and ciliary neurotrophic factor (CNTF) were added to trigger the lesioned area repair. This device enables NGF testing and environmental testing for assessing conditions for regrowth after neuronal axonal injury. As shown in Figure 4A, the microfluidic device consists of two compartments and an axotomy channel (100 \(\upmu\)m \(\times\) 100 \(\upmu\)m \(\times\) 12,000 \(\upmu\)m) to perform vacuum-assisted axotomy. The medium inside the axotomy channel was aspirated using a P20 micropipette set at 15 \(\upmu\)L, forming a tight seal between the tip and the outlet well (\(\mathcal{O}\) = 1.25 mm). Air bubbles were introduced inside the axotomy channel and fresh medium was then reintroduced through the inlet well. [PERSON], [PERSON] [64] designed a novel valve-based microfluidic device for axon injury and regrowth. this device can regulate air pressure through several valves to cause controlled micro-compression damage on the axon. In the work of [PERSON], [PERSON] [54], the microfluidic device can provide a 3D microenvironment with temporal and spatial adjustable gradients of NGF concentration to repair CNS neural axon injured by 6-hydroxopamine (6-OHDA). 6-OHDA was injected from three inlets to cause neurodegeneration to the neurons. After rewashing the residual 6-OHDA in the central channel, different concentrations of collagen hydrogel and natural products were used to promote the regeneration of the axon. In the research of [PERSON], [PERSON] et al. [21], the PDMS microfluidic chip was designed as a four-layered structure with size of 3.0 cm \(\times\) 3.0 cm. Figure 4B shows the schematic diagram of the chip and experiment process of neuronal degeneration and regeneration after chemical ACR injury. [PERSON] [65] presented a reproducible microfluidic method to simulate in vitro mechanical lesion of hundreds of axons simultaneously in a controlled manner. As shown in Figure 4C, the structure of the device is based on the basic model with the addition of compression damage device. The dimensions of the induced axonal injury and its distance from the neuronal cell body are precisely controlled while preserving both the proximal and distal portions of axons. [PERSON] [66] presented a microfluidic-microelectrode device to study the regeneration of neurons andits process by different concentrations of neurotrophic factors. The model is based on the structure shown in Figure 2A; the microelectrode array is equipped above the Somal compartments and records the electrical activity of growing neurites.