Open-architecture Neural Probes Reduce Cellular Encapsulation
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Open-architecture Neural Probes Reduce Cellular Encapsulation John Seymour, and Daryl Kipke Biomedical Engineering, University of Michigan, 1107 Gerstacker, 2200 Bonisteel, Ann Arbor, MI, 48109
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. INTRODUCTION The failure mode of chronic neural probe recordings has been linked to the foreign body response. Histological examination has consistently shown that a glial scar forms around the probe tract [1-3]. An increase in electrical impedance is concomitant with the time course of this reactivity and is therefore believed to be the cause of attenuated and noisy signal recordings [46]. Researchers are investigating a variety of techniques to prevent neuronal loss and cellular encapsulation by modulating the acute immune response and long-term reactivity (see Polikov for revie
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