Histological evaluation of flexible neural implants; flexibility limit for reducing the tissue response?

• Published in: Journal of neural engineering Vol. 14; no. 3; p. 036026
• Main Authors: Lee, Heui Chang, Ejserholm, Fredrik, Gaire, Janak, Currlin, Seth, Schouenborg, Jens, Wallman, Lars, Bengtsson, Martin, Park, Kinam, Otto, Kevin J
• Format: Journal Article
• Language: English
• Published: England IOP Publishing 01.06.2017
• Subjects: Animals; Annan medicinteknik; Brain Injuries - etiology; Brain Injuries - pathology; Brain Injuries - prevention & control; chronic neural implant; Elastic Modulus; Electrodes, Implanted - adverse effects; Electrodes, Implanted - classification; Engineering and Technology; Equipment Design; Equipment Failure Analysis; flexible brain-computer interface (fBCI); foreign body response (FBR); Foreign-Body Reaction - etiology; Foreign-Body Reaction - pathology; Foreign-Body Reaction - prevention & control; Medical Engineering; Medicinteknik; Mice; Microelectrodes - adverse effects; Microelectrodes - classification; Neural Prostheses - adverse effects; Neural Prostheses - classification; neuroprosthetics; off-stoichiometry thiol-enes (OSTE); Other Medical Engineering; Reproducibility of Results; Sensitivity and Specificity; Stress, Mechanical; Teknik
• ISSN: 1741-2560; 1741-2552
• DOI: 10.1088/1741-2552/aa68f0

Objective. Flexible neural probes are hypothesized to reduce the chronic foreign body response (FBR) mainly by reducing the strain-stress caused by an interplay between the tethered probe and the brain's micromotion. However, a large discrepancy of Young's modulus still exists (3-6 orders of magnitude) between the flexible probes and the brain tissue. This raises the question of whether we need to bridge this gap; would increasing the probe flexibility proportionally reduce the FBR? Approach. Using novel off-stoichiometry thiol-enes-epoxy (OSTE+) polymer probes developed in our previous work, we quantitatively evaluated the FBR to four types of probes with different softness: silicon (~150 GPa), polyimide (1.5 GPa), OSTE+Hard (300 MPa), and OSTE+Soft (6 MPa). Main results. We observed a significant reduction in the fluorescence intensity of biomarkers for activated microglia/macrophages and blood-brain barrier (BBB) leakiness around the three soft polymer probes compared to the silicon probe, both at 4 weeks and 8 weeks post-implantation. However, we did not observe any consistent differences in the biomarkers among the polymer probes. Significance. The results suggest that the mechanical compliance of neural probes can mediate the degree of FBR, but its impact diminishes after a hypothetical threshold level. This infers that resolving the mechanical mismatch alone has a limited effect on improving the lifetime of neural implants.