Following spinal cord injury, secondary injury and the formation of a glial scar create an environment that does not foster axonal regeneration. Therefore, those sustaining spinal cord injury have some form of functional deficit below the level of injury. With increasing frequency, scientists and engineers are developing biomaterial scaffolds to help promote axonal regeneration into and through the lesion site. While no biomaterial strategy is used clinically, several strategies show promise within animal models of spinal cord injury. Recently, our group discovered that electrospun fiber scaffolds are able to facilitate robust regeneration of axons within a complete transection spinal cord injury model. Results from this study also demonstrated that astrocytes migrated extensively into the biomaterial conduct, instead of forming the typical glial scar that surrounds the lesion site. In this application, we seek to bettr understand astrocytic response to topography and uncover the possible mechanisms by which topographically changed astrocytes facilitate neuroprotection and axonal regeneration following acute spinal cord injury.
Aims 1 and 2 of the application attempt to elucidate how astrocytes are phenotypically changed by fibers and if these phenotypic changes are altered by motor neuron presence. Additionally, we will examine the ability of these astrocytes to protect neurons from glutamate excitotoxicity. Lastly, in Aim 3, we will employ electrospun fibers within hemisection and contusive models of rat, acute SCI and examine astrocyte phenotypic changes, neuroprotective benefits and the ability of electrospun fibers to promote spinal cord regeneration and functional recovery. In conclusion, understanding the mechanisms by which biomaterials change astrocytes, in ways that support axonal regeneration, may lead to development of a biomaterial treatment option for those who suffer from acute spinal cord injury.

Public Health Relevance

Electrospun fibers have the ability to promote axonal regeneration within animal models of spinal cord injury (SCI). Using electrospun fibers, astrocytes, typically known to form a glial scar that inhibits axonal regeneration, actually migrat into the biomaterial conduit and support axonal regeneration through mechanisms not yet fully understood. It is postulated that if we can understand the mechanisms by which electrospun fibers change astrocytes, new methods and procedures to promote spinal cord regeneration may be uncovered. The neuro-protective characteristics of astrocytes will be tested when astrocytes are cultured onto different poly-L-lactide electrospun fibers of varying diameter. Electrospun fibers will then be implanted within rat acute contusion and hemisection injury models. Within these models, astrocyte migration into the lesion will be assessed and we will characterize the phenotypic changes in these astrocytes. After completing the experiments specified in the application, a better understanding of astrocyte changes induced by electrospun fibers will be uncovered.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
1R01NS092754-01
Application #
8941719
Study Section
Biomaterials and Biointerfaces Study Section (BMBI)
Program Officer
Jakeman, Lyn B
Project Start
2015-07-15
Project End
2020-04-30
Budget Start
2015-07-15
Budget End
2016-04-30
Support Year
1
Fiscal Year
2015
Total Cost
$265,407
Indirect Cost
$90,407
Name
Rensselaer Polytechnic Institute
Department
Biomedical Engineering
Type
Schools of Engineering
DUNS #
002430742
City
Troy
State
NY
Country
United States
Zip Code
12180
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