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Open-architecture Neural Probes Reduce Cellular Encapsulation

Published online by Cambridge University Press:  01 February 2011

John Seymour  and
Daryl Kipke
John Seymour
Affiliation:
[email protected], University of Michigan, Biomedical Engineering, 4719 293rd St, Toledo, OH, 43611, United States
Daryl Kipke
Affiliation:
[email protected], University of Michigan, Biomedical Engineering, 1107 Gerstacker, 2200 Bonisteel, Ann Arbor, MI, 48109, United States
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Abstract

Intracortical microelectrodes currently have the greatest potential for achieving a functional neural prosthesis in patients with neurodegenerative diseases or spinal cord injury. Device efficacy is lacking in long-term performance as seen in both chronological histology and biopotential recording studies.

Some researchers have shown that small single polymer fibers (less than 7-μm diameter) do not induce an encapsulation layer in the rat subcutis so we have extended this concept to neural probe design. In this experiment we investigated the brain-tissue response of polymer probes with 4-μm feature sizes that are capable of withstanding insertion forces when penetrating the rat neocortex. This polymer probe has both a stiff penetrating shank (70-μm by 42-μm) and fine polymer structures (4-μm by 5-μm) that extend laterally from the shank. Our testing verifies that despite a flexible substrate and small dimensions, these devices are mechanically robust and practical as neural probes. We developed a microfabrication process using SU-8 and parylene to create the relatively thick probe shank and thin lateral arms.

In vivo testing was conducted on seven Sprague-Dawley rats. These parylene devices were chronically implanted in the motor cortex for 4-weeks and then imaged using fluorescence microscopy. Cellular encapsulation and neuronal loss were assessed using a Hoechst counterstain and the immunomarker NeuN (neuronal nuclei).

The tissue reactivity immediately around the fine-feature structures is greatly reduced, showing mild cell encapsulation (90±68% increase) relative to the probe shank (460±320% increase). Neuronal loss was only (21±25%) out to 25-μm relative to significant loss around the probe shank (47±19%). Additionally, laminin+, fibronectin+, and Ox42+ tissue often showed greater intensity and thickness at the shank, indicating that the dense scar formation typical of cortical implants was mitigated around the fine lateral structure.

These results suggest that using MEMS-based microfabrication to create sub-cellular structures will significantly reduce encapsulation, which should extend the longevity of neural probes. We also believe this concept could be beneficial to any implantable sensor capable of scaled geometries.

Keywords

microelectro-mechanical (MEMS)tissuesensor
Type
Research Article
Information
MRS Online Proceedings Library (OPL) , Volume 926: Symposium CC – Electrobiological Interfaces on Soft Substrates , 2006 , 0926-CC02-04
Copyright
Copyright © Materials Research Society 2006

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References

1. Stensaas, S.S. and Stensaas, L.J., Histopathological evaluation of materials implanted in the cerebral cortex. Acta Neuropathol (Berl), 1978. 41(2): p. 145–55.Google Scholar
2. Szarowski, D.H., et al., Brain responses to micro-machined silicon devices. Brain Res, 2003. 983(1-2): p. 23–35.Google Scholar
3. Biran, R., Martin, D.C., and Tresco, P.A., Neuronal cell loss accompanies the brain tissue response to chronically implanted silicon microelectrode arrays. Exp Neurol, 2005. 195(1): p. 115–26.Google Scholar
4. Liu, X., et al., Stability of the interface between neural tissue and chronically implanted intracortical microelectrodes. IEEE Transactions on Rehabilitation Engineering, 1999. 7(3): p. 315–26.Google Scholar
5. Ludwig, K.A., et al., Chronic neural recordings using silicon microelectrode arrays electrochemically deposited with a poly(3,4-ethylenedioxythiophene) (PEDOT) film. J Neural Eng, 2006. 3(1): p. 59–70.Google Scholar
6. Rousche, P.J. and Normann, R.A., Chronic recording capability of the Utah Intracortical Electrode Array in cat sensory cortex. Journal of Neuroscience Methods, 1998. 82(1): p. 1–15.Google Scholar
7. Polikov, V.S., Tresco, P.A., and Reichert, W.M., Response of brain tissue to chronically implanted neural electrodes. J Neurosci Methods, 2005. 148(1): p. 1–18.Google Scholar
8. Sanders, J.E., Stiles, C.E., and Hayes, C.L., Tissue response to single-polymer fibers of varying diameters: evaluation of fibrous encapsulation and macrophage density. J Biomed Mater Res, 2000. 52(1): p. 231–7.Google Scholar
9. Sanders, J.E., et al., Small fiber diameter fibro-porous meshes: Tissue response sensitivity to fiber spacing. J Biomed Mater Res A, 2005. 72A(3): p. 335–42.Google Scholar
10. Chen, C.S., et al., Geometric control of cell life and death. Science, 1997. 276(5317): p. 1425–8.Google Scholar
11. Chen, C.S., Tan, J., and Tien, J., Mechanotransduction at cell-matrix and cell-cell contacts. Annu Rev Biomed Eng, 2004. 6: p. 275–302.Google Scholar
12. Vetter, R.J., et al., Chronic neural recording using silicon-substrate microelectrode arrays implanted in cerebral cortex. IEEE Trans Biomed Eng, 2004. 51(6): p. 896–904.Google Scholar
13. Shearer, M.C. and Fawcett, J.W., The astrocyte/meningeal cell interface--a barrier to successful nerve regeneration? Cell Tissue Res, 2001. 305(2): p. 267–73.Google Scholar
14. Williams, J.C., Rennaker, R.L., and Kipke, D.R., Long-term neural recording characteristics of wire microelectrode arrays implanted in cerebral cortex. Brain Res Brain Res Protoc, 1999. 4(3): p. 303–13.Google Scholar