Control of Neural Growth and Connectivity in Engineered 2D and 3D Platforms

Description

Injury or degradation in the brain could cause life-long disabilities. About 17,000 per year suffer from spinal cord injury (SCI) in the United States, and there are 27 million prevalent cases of SCI worldwide. For traumatic brain injury, more than 20 million cases are serious enough to require hospitalization or even cause death in the world. The failure to regenerate injured axons and rebuild neural connections within the central nervous system is the primary cause for permanent disabilities following trauma or disease. Hence, there is a critical need to develop a successful treatment that can fully reverse damage to the nervous system. Millions of people can benefit from novel, innovative treatments that could restore functions and lessen the afflictions of brain injury. We propose to develop 2D and 3D platforms with designed topography and precisely controlled guidance cues to promote neural growth through their interactions with the patterned surfaces. Neurons are expected to be guided to have unidirectional growth not only in the horizontal plane, but also in the vertical direction. This will be the first demonstration of controlling unidirectional neural growth in engineered 2D and 3D platforms with precisely controlled physical topography and patterned chemical coating. Guidance patterns with different dimensions and layouts will be developed to promote hippocampal neurite outgrowth. In order to provide effective guidance, the feature dimensions will be designed around the sizes of the cell, axon, and dendrite. Smaller dimensions and denser patterns are expected to promote better neurite alignment and outgrowth, but they may restrict neurite branching or formation of complete neurite network. The effectiveness of the neural guidance cues will be compared among physical topography, chemical patterns, and microchannels to test the importance of physical step, chemoattractant, and axon confinement. The influence of guidance patterns with different bending angles and curvatures will be studied to understand the competing elements of surface contact area and neurite growth with sharp bending.   Designed patterns will be used to promote unidirectional neurite outgrowth by three principles: asymmetry in guidance pattern, discontinuous pattern, and pattern with changing density. We will also study how guidance cues could promote the formation of functional neural connections. By placing neural guidance patterns in key positions, it is expected that neural connectivity will be enhanced and neurons could be controlled to grow in the vertical direction in 3D platforms. This unique capability of controlling the direction of neural growth not only on the horizontal surface, but also in the vertical direction can provide important insight in neural connectivity and regeneration.