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.
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.
Authors: Cort H Thompson; Ti'Air E Riggins; Paras R Patel; Cynthia A Chestek; Wen Li; Erin Purcell Journal: J Neural Eng Date: 2020-03-12 Impact factor: 5.379
Authors: Nicholas J Michelson; Alberto L Vazquez; James R Eles; Joseph W Salatino; Erin K Purcell; Jordan J Williams; X Tracy Cui; Takashi D Y Kozai Journal: J Neural Eng Date: 2017-11-28 Impact factor: 5.379
Authors: Jason E Chung; Hannah R Joo; Clay N Smyth; Jiang Lan Fan; Charlotte Geaghan-Breiner; Hexin Liang; Daniel Fan Liu; Demetris Roumis; Supin Chen; Kye Y Lee; Jeanine A Pebbles; Angela C Tooker; Vanessa M Tolosa; Loren M Frank Journal: J Vis Exp Date: 2019-10-04 Impact factor: 1.355
Authors: Jason E Chung; Hannah R Joo; Jiang Lan Fan; Daniel F Liu; Alex H Barnett; Supin Chen; Charlotte Geaghan-Breiner; Mattias P Karlsson; Magnus Karlsson; Kye Y Lee; Hexin Liang; Jeremy F Magland; Jeanine A Pebbles; Angela C Tooker; Leslie F Greengard; Vanessa M Tolosa; Loren M Frank Journal: Neuron Date: 2018-11-27 Impact factor: 17.173