PhD Defense Neural Engineering
Speaker: Danny Lam
Advisors: Profs. Shoffstall and Capadona
Location Nord 356
Abstract: Bioelectronic medicine is a promising approach for treating various neurological disorders that current treatments are ineffective or result in undesirable side effects. Neural interfaces enable physicians to electrically “communicate” with the nervous system and influence its activity. Despite advancements in neural interfaces, the placement of implantable devices during and after surgery poses additional risks when evaluating therapies.
Tissue trauma from surgery can amplify the foreign body response to implants, hindering tissue recovery and reducing the therapeutic benefit of neural interfaces. Consequently, the invasiveness of surgical procedures may lead to increased healthcare expenses and ultimately impede the widespread clinical utilization and adoption of these implanted devices.The overarching goal of this talk was to explore innovative strategies that could potentially alleviate the tissue trauma associated with implantable devices, a crucial step toward advancing bioelectronic medicine. The specific aims in this work were to:
1. Investigate the potential relationship of platelets and other blood components in the chronic neuroinflammatory environment of implanted neural interfaces.
2. Evaluate the performance of a new electrode architecture consisting of flexible microwires for chronic applications of peripheral nerve stimulation.
3. Develop a bioabsorbable electrode platform for temporary applications of peripheral nerve stimulation.
The first study explored the influence of hemostasis and coagulation contributors on the inflammatory activity at the electrode-tissue interface for implanted intracortical microelectrodes. My findings revealed that platelets and hemostatic proteins, such as von Willebrand Factor, fibrinogen, and collagen, persist and locally concentrate up to 150 µm from the electrode-tissue interface for at least 8 weeks post-implantation in a rat model. When used in conjunction with conventional biomarkers of neuroinflammation, these biomarkers could potentially indicate long-term instability and dysfunction of the blood-brain barrier. This significant discovery enhances our comprehension of the chronic neuroinflammatory environment resulting from implanted neural interfaces, paving the way for future therapies that minimize tissue trauma and its downstream effects on neural recording performance.
In the second study, I assessed a new peripheral nerve electrode platform designed to simplify its implantation and removal. Microwires were coiled into an open helix configuration to withstand substantial mechanical deformations, reducing the risk of lead breakage and fragmentation, which can trigger an aggressive foreign body response. Ankle flexion was successfully evoked in a subset of rats in response to sciatic nerve stimulation for at least 8 weeks, highlighting the electrode’s initial feasibility as a neural interface for chronic applications.
In the third study, I addressed the need for temporary solutions where a permanent device may not be necessary. A transient electrode platform was developed using off-the-shelf bioabsorbable sutures coated with 100 nanometer-thin layers of gold. These conductive sutures were shown to have ideal bench properties to function as a neural interface for up to 2 weeks. Implanted conductive sutures could effectively induce muscle contractions in response to nerve stimulation for up to 2 days while maintaining its conductive properties for at least 4 weeks. The development of bioabsorbable electrodes could offer a safe and efficient method for delivering electrical stimulation to nerves during the evaluation of stimulation therapy while minimizing associated risks.
These studies were conducted independently, each leveraging different expertise and skills to develop and evaluate new strategies to mitigate tissue trauma associated with implantable devices. The outcomes of this collective effort not only underscore the intricacies of addressing application-specific biocompatibility issues of implantable neural interfaces but also offer practical solutions to improve their reliability.