Nerves fail to regenerate after injury and current medical practice is unable to manipulate effectively the process of nerve regeneration. This project will quantify how guidance cues, both individually and in combination, promote axon growth. The research results will provide an understanding of nerve development and of accurate and effective nerve regeneration. The goal of this proposal is to study the guidance of axons by multiple cues, including topography and specific molecules on surfaces, using microfabrication and microfluidics.
The educational plan focuses on increasing oral communication skills, namely public speaking, of undergraduate and first year graduate students. The students in two classes that the principal investigator (PI) teaches will give seminars to non-scientific audiences. The PI will also run a workshop to help faculty teach communication skills in their classes.
, Diane Hoffman-Kim has developed a research program to address the fundamental science of nerve repair technology and focus on the neuronal environment at the micro- and nanoscales. Work has focused on deconstructing the multiple, disorganized cues that neurons face at the site of injury. By developing innovative in vitro systems to reveal the growth responses of nerve cells to guidance cues, a goal is to determine the key parameters required to design technologies for successful nerve repair. Broader impacts have been achieved in the areas of training of female engineers and development of a program to communicate science and engineering to non-science audiences. Research highlights include: One of the outstanding questions in nerve repair is how neurons interpret the complex mixture of inhibitory and permissive cues that are present after injury. Our group’s work on multi-molecular gradients generated well-defined gradients containing two contrasting guidance cues present in post-injury scars. This work has shown that neurons incorporate information from both cues and direction. We have also demonstrated complex neurite responses to multiple cues presented at the interface of 2D and 3D environments. In the peripheral nervous system, supportive Schwann cells promote nerve regeneration by providing neurons with multiple cues. Which cues are critical for guidance has not yet been determined. Our group’s development of biomimetic materials that replicate the topography of Schwann cells has allowed us to carry out the first investigation of the role of cellular topography in directing nerve growth. We have found that neurons grow faster on materials with Schwann cell topography than on flat materials, and they direct their neurites along the Schwann cell patterns. These results suggest that microscale and nanoscale topographical cues provided by Schwann cells influence nerve growth, and point toward design parameters for future nerve repair technologies. My group is continuing its work in characterizing the dynamic neuronal response to these materials, and developing nerve guidance channels to promote nerve regeneration in vivo.
