4.8 Article

The relationship between glial cell mechanosensitivity and foreign body reactions in the central nervous system

Journal

BIOMATERIALS
Volume 35, Issue 13, Pages 3919-3925

Publisher

ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2014.01.038

Keywords

Gliosis; Implant; FBR; Astrocyte; Microglia; Stiffness

Funding

  1. Cambridge Overseas Trust
  2. UK Engineering and Physical Sciences Research Council
  3. European Union
  4. MRC Centre for Obesity and Related Metabolic Disorders
  5. UK Biotechnology and Biological Sciences Research Council
  6. Christopher and Dana Reeves Foundation
  7. Human Frontier Science Program
  8. Marie Curie Initial Training Network Transpol
  9. Alexander von Humboldt Foundation
  10. UK Medical Research Council
  11. Biotechnology and Biological Sciences Research Council [BB/H021930/1] Funding Source: researchfish
  12. Engineering and Physical Sciences Research Council [EP/H00727X/1] Funding Source: researchfish
  13. Medical Research Council [1508875, G1100312, G1000864] Funding Source: researchfish
  14. BBSRC [BB/H021930/1] Funding Source: UKRI
  15. EPSRC [EP/H00727X/1] Funding Source: UKRI
  16. MRC [G1000864, G1100312] Funding Source: UKRI

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Devices implanted into the body become encapsulated due to a foreign body reaction. In the central nervous system (CNS), this can lead to loss of functionality in electrodes used to treat disorders. Around CNS implants, glial cells are activated, undergo gliosis and ultimately encapsulate the electrodes. The primary cause of this reaction is unknown. Here we show that the mechanical mismatch between nervous tissue and electrodes activates glial cells. Both primary rat microglial cells and astrocytes responded to increasing the contact stiffness from physiological values (G' similar to 100 Pa) to shear moduli G' >= 10 kPa by changes in morphology and upregulation of inflammatory genes and proteins. Upon implantation of composite foreign bodies into rat brains, foreign body reactions were significantly enhanced around their stiff portions in vivo. Our results indicate that CNS glial cells respond to mechanical cues, and suggest that adapting the surface stiffness of neural implants to that of nervous tissue could minimize adverse reactions and improve biocompatibility. (C) 2014 The Authors. Published by Elsevier Ltd. All rights reserved.

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