4.6 Article

Mechanically-compliant intracortical implants reduce the neuroinflammatory response

Journal

JOURNAL OF NEURAL ENGINEERING
Volume 11, Issue 5, Pages -

Publisher

IOP PUBLISHING LTD
DOI: 10.1088/1741-2560/11/5/056014

Keywords

biomimetic material; intracortical microelectrode; foreign body response; mechanical properties; nanocomposite

Funding

  1. Department of Biomedical Engineering at Case Western Reserve University through laboratory start-up funds (Capadona)
  2. Department of Veterans Affairs, Veterans Health Administration, Rehabilitation Research and Development Service: Career Development Award (Capadona) [B6344W]
  3. Merit Review (Capadona) [B7122R]
  4. Advanced Platform Technology Center [C3819C]
  5. Presidential Early Career Award for Scientists and Engineers (PECASE, Capadona)
  6. National Institutes of Health: National Institute of Biomedical Imaging and Bioengineering Integrated Engineering and Rehabilitation Training Program [5T32EB004314-15]
  7. National Institute of Neurological Disorders and Stroke (Capadona) [R01-NS082404-01A1]
  8. National Institute of Neurological Disorders and Stroke (Tyler) [R21-NS053798]
  9. National Science Foundation [CBET-0828155, DMR-0804874, DMR-1204948]
  10. Swiss National Science Foundation (NRP 62: Smart Materials) [406240_126046]
  11. Adolphe Merkle Foundation

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Objective. The mechanisms underlying intracortical microelectrode encapsulation and failure are not well understood. A leading hypothesis implicates the role of the mechanical mismatch between rigid implant materials and the much softer brain tissue. Previous work has established the benefits of compliant materials on reducing early neuroinflammatory events. However, recent studies established late onset of a disease-like neurodegenerative state. Approach. In this study, we implanted mechanically-adaptive materials, which are initially rigid but become compliant after implantation, to investigate the long-term chronic neuroinflammatory response to compliant intracortical microelectrodes. Main results. Three days after implantation, during the acute healing phase of the response, the tissue response to the compliant implants was statistically similar to that of chemically matched stiff implants with much higher rigidity. However, at two, eight, and sixteen weeks post-implantation in the rat cortex, the compliant implants demonstrated a significantly reduced neuroinflammatory response when compared to stiff reference materials. Chronically implanted compliant materials also exhibited a more stable blood-brain barrier than the stiff reference materials. Significance. Overall, the data show strikingly that mechanically-compliant intracortical implants can reduce the neuroinflammatory response in comparison to stiffer systems.

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