The focus of this study is to investigate the role of substrate stiffness in the tissue response to cortical implants in order to create a longer-lasting, more intimate interface with neural tissue. Cortical electrodes have already shown great advances in neuroscience to help understand the structure and function of the brain. Applications to restore motor function to neurologically impaired individuals have shown promise to restore functionality. Cortical electrodes have been unable to achieve the longevity and stability to be employed as a viable clinical option. A constraint on longevity is the formation of a glial scar around an implant. It is proposed that reactions are due to two modes: a macro mode and a micro mode. The macro mode is a shear stress, differential-motion effect caused by a hard implant in soft neural tissue. The micro mode is a mechanotransduction mechanism where cellular pathways activate based on substrate stiffness.
The first aim will investigate the cell micro/durotaxis response by using a controllable-stiffness material system to analyze the cellular response via immunohistochemistry (IHC).
The second aim will investigate the effect of macro/shear stress by using a mechanically dynamic nanocomposite to gauge tissue response via IHC.
The third aim i s to assess the tissue response via electrophysiology by using a nanocomposite- encapsulated electrode. Immunohistochemisty of implants and electrophysiology of electrodes will provide quantitative data to differentiate performance of materials. The proposed work is designed to fuse neuroscience and neural engineering viewpoints to merge the fields to understand the fundamentals that will be vital in curing neural disorders and designing future neural devices. The focus of the study is on the cellular response to implant stiffness, and information gained in this study will be broadly applicable to many health arenas. Material stiffness has been implicated in stem cell differentiation, cancer development, spinal cord regrowth, and tissue engineering among other fields. Increasing the longevity of cortical implants will also allow for clinical restoration of function and the investigation of neurological diseases. This study will provide the first comprehensive study of stiffness- based tissue responses to cortical implants in vivo.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31NS063640-02
Application #
7826970
Study Section
Special Emphasis Panel (ZRG1-F03B-H (20))
Program Officer
Kleitman, Naomi
Project Start
2009-04-10
Project End
2012-03-31
Budget Start
2010-04-01
Budget End
2011-03-31
Support Year
2
Fiscal Year
2010
Total Cost
$41,380
Indirect Cost
Name
Case Western Reserve University
Department
Biomedical Engineering
Type
Schools of Engineering
DUNS #
077758407
City
Cleveland
State
OH
Country
United States
Zip Code
44106
Harris, J P; Capadona, J R; Miller, R H et al. (2011) Mechanically adaptive intracortical implants improve the proximity of neuronal cell bodies. J Neural Eng 8:066011
Harris, J P; Hess, A E; Rowan, S J et al. (2011) In vivo deployment of mechanically adaptive nanocomposites for intracortical microelectrodes. J Neural Eng 8:046010