Seeding neural progenitor cells on silicon-based neural probes.
OBJECTIVE
Chronically implanted neural electrode arrays have the potential to be used as neural prostheses in patients with various neurological disorders. While these electrodes perform well in acute recordings, they often fail to function reliably in clinically relevant chronic settings because of glial encapsulation and the loss of neurons. Surface modification of these implants may provide a means of improving their biocompatibility and integration within host brain tissue. The authors proposed a method of improving the brain-implant interface by seeding the implant's surface with a layer of neural progenitor cells (NPCs) derived from adult murine subependyma. Neural progenitor cells may reduce the foreign body reaction by presenting a tissue-friendly surface and repair implant-induced injury and inflammation by releasing neurotrophic factors. In this study, the authors evaluated the growth and differentiation of NPCs on laminin-immobilized probe surfaces and explored the potential impact on transplant survival of these cells.


METHODS
Laminin protein was successfully immobilized on the silicon surface via covalent binding using silane chemistry. The growth, adhesion, and differentiation of NPCs expressing green fluorescent protein (GFP) on laminin-modified silicon surfaces were characterized in vitro by using immunocytochemical techniques. Shear forces were applied to NPC cultures in growth medium to evaluate their shearing properties. In addition, neural probes seeded with GFP-labeled NPCs cultured in growth medium for 14 days were implanted in murine cortex. The authors assessed the adhesion properties of these cells during implantation conditions. Moreover, the tissue response around NPC-seeded implants was observed after 1 and 7 days postimplantation.


RESULTS
Significantly improved NPC attachment and growth was found on the laminin-immobilized surface compared with an unmodified control before and after shear force application. The NPCs grown on the laminin-immobilized surface showed differentiation potential similar to those grown on polylysine-treated well plates, as previously reported. Viable (still expressing GFP) NPCs were found on and in proximity to the neural implant after 1 and 7 days postimplantation. Preliminary examinations indicated that the probe's NPC coating might reduce the glial response at these 2 different time points.


CONCLUSIONS
The authors' findings suggest that NPCs can differentiate and strongly adhere to laminin-immobilized surfaces, providing a stable matrix for these cells to be implanted in brain tissue on the neural probe's surface. In addition, NPCs were found to improve the astrocytic reaction around the implant site. Further in vivo work revealing the mechanisms of this effect could lead to improvement of biocompatibility and chronic recording performance of neural probes.
Department of Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA. era14@pitt.edu
Erdrin
E
Azemi
Glenn T
GT
Gobbel
Xinyan Tracy
XT
Cui
D053687:Adult Stem Cells / Q000502:physiology*; D000818:Animals; D001253:Astrocytes / Q000502:physiology; D002448:Cell Adhesion; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D002470:Cell Survival; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000502:physiology / Q000601:surgery; D049452:Green Fluorescent Proteins / Q000378:metabolism; D007797:Laminin; D055595:Mechanical Phenomena; D055495:Neurogenesis; D009474:Neurons / Q000502:physiology*; D051381:Rats; D011916:Rats, Inbred F344; D012825:Silicon; D013997:Time Factors; D023822:Tissue Engineering / Q000295:instrumentation* / Q000379:methods*; D054457:Tissue Scaffolds
D007797:Laminin; D049452:Green Fluorescent Proteins; D012825:Silicon