TitleAn improved model for neurite guidance validated
to a novel micropatterned In vitro surrogate
NameVoyiadjis, Andrewv George (author), Shinbrot, Troy (chair), Buettner, Helen (internal member), Shreiber, David (internal member), Firestein, Bonnie (internal member), Zhou, Renping (outside member), Rutgers University, Graduate School - New Brunswick,
Nerves, Peripheral—Wounds and injuries,
DescriptionRecent research on repair mechanisms in injured spinal cords focuses on the regeneration of neurites across the injury site. While integral to developing a therapy, regeneration does not ensure that neurites will reach their specific targets and develop functional recovery. Regenerating neurites are less likely to reach their targets given their potential for misguided exploration. To understand how the presence of numerous branches (e.g., spinal roots) along a spinal column may affect a neurite’s route, we (1) created a computational (in silico) model of neurite outgrowth which was applied to a pattern that resembles a spinal column with multiple roots, (2) engineered an in vitro model with identical patterns which was evaluated and compared to the in silico model, and (3) modified the patterns for both models to test how restricting neurite exploration into non-target roots affects neurite guidance to target roots. The in silico model was constructed by analyzing dorsal root ganglion (DRG) neurite outgrowth on uniform laminin. We simulated a pattern that resembles a 2-dimensional simplification of a spinal column with multiple roots. From this model, we found that the likelihood of neurites reaching a root diminishes exponentially with root distance from the neurite’s initiation. For the in vitro model, neurites from E7 chick DRG explant cultures were grown on a micropattern, identical to the in silico model. In vitro and in silico neurite root preference were then compared, and were found to match significantly, thus validating the in silico model. Finally, to understand the affect of non-target roots on guidance to target roots, we modified both models by removing non-target roots. We found that neurites were successfully guided to target roots when misguiding roots were removed, but only when targets are distant from the neurite’s origin in both models. This research adds to the current understanding of neurite guidance in complex nervous systems and advances a predictive model for testing guidance strategies. Both of the in vitro and in silico models will enhance clinical or in vivo research, which focus on improving functional recovery following nervous system injury. These models will allow for a non-invasive, efficient, and cost effective way to test therapeutic guide strategies for treating nervous system injuries.
NoteIncludes bibliographical references
Noteby Andrew George Voyiadjis
CollectionGraduate School - New Brunswick Electronic Theses and Dissertations
Organization NameRutgers, The State University of New Jersey
RightsThe author owns the copyright to this work.