The research objective of this proposal is to develop a cost-effective and high-throughput technology using microelectrode arrays and polymer nanostructures that would generate controlled gradients of multiple guidance cues (GCs) for a systematic investigation of the effect of these cues on axons.

Nontechnical Abstract

Guidance of axons is vital for the development and repair of nervous system. It is known that axons navigate along specific pathways to their targets by relying on guidance mechanisms of gradients of attractive and repulsive cues that exist in their extracellular environment. Injuries to the central and peripheral nervous system (CNS and PNS) can result in severe functional loss. Spontaneous axonal regeneration is limited to small lesions within PNS and is actively suppressed within CNS. This study aims to develop a technology platform and enhance fundamental knowledge on the interactions between regenerating axons and their microenvironment. Through systematic investigation of the effect of gradients of different cues on the growth and guidance of axons, this research will pave the way for a solution to the major clinical problem of neural regeneration in peripheral and central nervous systems. According to the National Spinal Cord Injury Statistical Center, there are approximately 290,000 individuals in the US who suffer from spinal cord injuries with about 12,000 new injuries occurring each year. The findings of this research will, therefore, have a significant impact on public health. The educational objective of this proposal is to promote the participation of women and minorities in the field of biomedical science and neural engineering by creating multi-interdisciplinary training opportunities for high school, undergraduate, and graduate students. This work aims to: 1) integrate research and education through curriculum development, workshops, and training of students in an interdisciplinary environment; 2) open the pipeline at both high school to college and undergraduate to graduate levels for minorities by providing hands-on experiences.

Technical Abstract

Spontaneous axonal regeneration is limited to small lesions within injured peripheral nervous system (PNS) and is actively suppressed within central nervous system (CNS). While tissue-engineering strategies have been used for treatment of nerve injuries, regeneration of functional axons over long nerve gaps remains a challenge due to the complex post-injury physiological environment that contains multiple, often conflicting signals. An improved understanding of these signals and their integrated effect on regenerating axons is, hence, a prerequisite for development of effective therapies for nerve injuries. The research objective of this proposal is to develop a cost-effective and high-throughput technology using microelectrode arrays and polymer nanostructures that would generate controlled gradients of multiple distinct guidance cues (GCs) for systematic investigation of the effect of these cues on axons. Using the proposed technology, this research aims to: 1) study the effect of gradients of diffusible growth molecules on growing axons; 2) investigate the effect of gradients of surface cues on rate and direction of axonal growth; 3) study the effect of integration of gradients of multiple GCs on axonal regeneration in a 3D scaffold with the capability of monitoring axonal regeneration.

Project Start
Project End
Budget Start
2014-08-01
Budget End
2017-07-31
Support Year
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Pennsylvania State University
Department
Type
DUNS #
City
University Park
State
PA
Country
United States
Zip Code
16802