Abstract
The use of implants that allow chronic electrical stimulation and recording in the brain of human patients is currently limited by a series of events that cause the deterioration over time of both the electrode surface and the surrounding tissue. The main reason of failure is the tissue inflammatory reaction that eventually causes neuronal loss and glial encapsulation, resulting in a progressive increase of the electrode-electrolyte impedance. Here, we describe a new method to create bio-inspired electrodes to mimic the mechanical properties and biological composition of the host tissue. This combination has a great potential to increase the implant lifetime by reducing tissue reaction and improving electrical coupling. Our method implies coating the electrode with reprogrammed neural or glial cells encapsulated within a hydrogel layer. We chose fibrin as a hydrogel and primary hippocampal neurons or astrocytes from rat brain as cellular layer. We demonstrate that fibrin coating is highly biocompatible, forms uniform coatings of controllable thickness, does not alter the electrochemical properties of the microelectrode and allows good quality recordings. Moreover, it reduces the amount of host reactive astrocytes – over time – compared to a bare wire and is fully reabsorbed by the surrounding tissue within 7 days after implantation, avoiding the common problem of hydrogels swelling. Both astrocytes and neurons could be successfully grown onto the electrode surface within the fibrin hydrogel without altering the electrochemical properties of the microelectrode. This bio-hybrid device has therefore a good potential to improve the electrical integration at the neuron-electrode interface and support the long-term success of neural prostheses.
Highlights
Patients with various neurological disorders could benefit from the stereotaxic implant of chronic intracerebral microelectrodes to record endogenous activity and/or to electrically stimulate specific brain areas (Donoghue et al, 2007; Larson, 2008; Truccolo et al, 2008; Velliste et al, 2008; Benabid et al, 2009; Normann et al, 2009; Hemm and Wårdell, 2010)
Coating thickness was progressively increased by dipping the electrode in both fibrinogen and thrombin from 2 to 7 times
Once the electrode is implanted in-vivo, the swelling of the fibrin hydrogel coating increases the distance between the tissue and the electrode
Summary
Patients with various neurological disorders could benefit from the stereotaxic implant of chronic intracerebral microelectrodes to record endogenous activity and/or to electrically stimulate specific brain areas (Donoghue et al, 2007; Larson, 2008; Truccolo et al, 2008; Velliste et al, 2008; Benabid et al, 2009; Normann et al, 2009; Hemm and Wårdell, 2010). To be functional and safe, the implant should keep a stable electric interface with the tissue, enabling an efficient recording and/or activation of neurons over time. The long-term functionality of implanted electrodes has been very critical, because of the progressive deterioration of both the electrode surface and the surrounding neural tissue. The tissue is cut, stretched or compressed by the penetration of the electrode and neurons and glial cells within and around the electrode path are killed or severely injured during insertion. The deepening of the electrode into the brain pushes aside the tissue and increases the local pressure of the surrounding tissue. Blood vessels and capillaries are disrupted and the blood– brain barrier is compromised (Bjornsson et al, 2006), leading to plasma extravasation and local edema, that further increase the intracranial pressure (Unterberg et al, 2004)
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