# A Review on Microfluidic Platforms Applied to Nerve Regeneration
## 5 Challenges, Future Perspectives and Conclusions  
In this review, we introduce the development and recent advances of microfluidic platforms for neural regeneration research. Various microfluidic platforms and devices are classified and discussed according to neural injury models, approaches of axon guidance and mechanisms of neural regeneration such as axon regeneration/repair and neurite outgrowth/regrowth. Here, we outline the characteristics and advantages of cell cultures in microfluidic platform over traditional in vitro culture methods. The technological development from 2D culture models to complex 3D culture models is described in terms of materials and structures. The microfluidic platforms provide strong technological support for in vitro cell culture research. As seen from the trend of the last three decades, microfluidic platforms are gradually becoming an important tool for the study of neural regeneration. Microfluidic platforms enable accurate simulation of the in vivo micro-environment for different neurobiological studies such as analyzing myelin growth inhibitory factors, screening drugs and NGFs that promote axonal growth, and exploring mechanisms of injury and regeneration. Precise and complex manipulation of neuronal cells can be achieved through microfluidic platforms, such as isolation and manipulation of single neuron, cultured neuron patterning, control of neurite outgrowth and axon guidance. In some studies, microfluidic platforms are integrated with other systems, such as fluid concentration gradient generation devices, optical microscope and millisecond laser, to meet different experimental requirements. However, microfluidic platforms have not yet revealed their full potential in the field of biological experiments. There are still some challenges and limitations of microfluidic platforms for neural regeneration. First, there are no suitable 3D injury models for complete SCI. Current microfluidic-based 3D culture models cannot closely simulate the complex environment of inside the damaged vertebral canal. Moreover, it is deemed incapable to accurately reconstruct the spatial structure of post-injury spinal cord tracts. It results in nerve regeneration methods that work well at the cellular level in vitro but are ineffective in the in vivo environment. Second, current regeneration studies based on microfluidics are not sufficiently standardized. Numerous nerve injury models and repair approaches have been developed; however, there is not a unified assessment criteria to quantitatively detect and evaluate the efficacy of drugs. Microfluidic nerve regeneration is a highly interdisciplinary research field. Models for neural regeneration study are proposed by biologists; however, microfluidic cell culture platforms often rely on complex external control systems, which involves many physicochemical parameters and variables. This leads to different standards and parameters involved in similar experiments. Finally, microfluidic platforms can greatly mimic the in vivo micro-environment and provide ideal experimental conditions for nerve regeneration. However, the study of nerve regeneration still remains in vitro, especially in CNS regeneration studies. There are many technical obstacles to progress from in vitro to in vivo studies. We expect that microfluidic platforms will be more widely used, not only in the field of neural regeneration, but also in all cellular and neurobiological research. Although, 2D cell culture are currently widely used and many breakthroughs are made on 2D culture microfluidic platforms. The 3D culture microfluidics have a much greater potential for future cell regeneration research. More microfluidic platforms for 3D culture will be developed to break through the limitations of existing 3D culture models and better mimic the 3D environment in vivo.