The purpose of this award is to provide Dr. Andrew Shoffstall the training he requires to become a successful researcher within the VA system. During his doctoral training, Dr. Shoffstall focused on the development of synthetic platelets to reduce bleeding after trauma (including after traumatic brain or spinal cord injury). Bleeding in the central nervous system (CNS, brain and spinal cord) initiates an inflammatory cascade that exacerbates the original injury. As a result of his training, he realized there was an unmet need to better understand and mitigate bleeding that occurs after surgical implantation of medical devices (e.g., electrodes, shunts, etc.) in the CNS. Neuromodulation applications (e.g. deep brain or spinal cord stimulation) are rapidly growing, both in use among clinicians and variety of conditions in which it is being applied. Furthermore, encouraging advances are being made in novel applications such as brain-computer interface (BCI) to control robotic prosthetic limbs or neuroprostheses. Such technology requires surgical implantation of electrodes in the brain and invariably results in bleeding that initiates an inflammatory cascade that may negatively impact the long-term stability or functionality of the device. Presently, the candidate seeks to gain additional experience in neuroinflammation, the downstream impact of bleeding in the CNS. Partnered with his primary mentor, Dr. Jeffrey Capadona, the candidate?s project will investigate the role of material stiffness in the inflammatory response observed following implantation of microelectrodes in the brain cortex. Microelectrodes that are currently used BCI applications demonstrate poor neural recording performance and reliability (e.g. signal-to-noise ratio degrades over several weeks-to-months). Inflammation, due in part to the mechanical mismatch stiff electrode material and soft brain tissue, is thought to be a major contributing factor to the observed signal degradation. Using state-of-the art polymer science, Dr. Voit (an informal mentor) has developed a tunable shape-memory- polymer microelectrode material that dynamically changes its stiffness in response to temperature change. As a result, microelectrodes may be fabricated with a range of stiffness while still maintaining similar size and chemistry. Therefore, this enables for the first time, the systematic testing of the hypothesis that dynamically softening microelectrodes will demonstrate an attenuated inflammatory response compared to size- and chemistry- matched non-softening microelectrodes. To test the hypothesis, Dr. Shoffstall will implant microelectrodes made of Dr. Voit?s novel material, with varying stiffness, in rat cortex and assay the inflammatory response using immunohistochemistry (Aim 1). He will be mentored in these tasks by Drs. Capadona and Tyler on his mentoring committee. In addition, mentored by Dr. Capadona, he will assess motor function through a battery of behavioral tests to determine if device stiffness reduces damage to the motor cortex as has been observed (and demonstrated in Preliminary Evidence) by the Capadona lab with stiff silicon microelectrodes (Aim 2). Conducting the research in Aim 2 will provide the candidate with experience in functional behavioral techniques that he may leverage in the future to continuously monitor the inflammatory and subsequent healing response to implanted materials in the CNS. Together, these two aims align well with the primary mentor?s funded research and provide the candidate to learn vital techniques that will aid him in achieving his career goals. In addition to experience gained through research tasks, the candidate will benefit from key professional development experience: writing papers with his mentoring committee members, preparing his CDA-2 application, shadowing physicians that implant neuromodulation technologies (e.g., Dr. Veizi), and engaging in continuous dialog with his mentors.
Implanted medical devices in the central nervous system (CNS) are used for a number of current and future applications including control of tremor (Parkinson?s disease, ~60,000 Veterans?), pain block/relief (chronic pain, >30 million US?), shunting cerebrospinal fluid (hydrocephalous, ~24,000 Veterans?), and brain-controlled prostheses (spinal cord injury paralysis, ~50,000 Veterans?), among others (?: prevalence). Chronic inflammation may reduce the longevity and performance of CNS-implanted devices. During the candidate?s career, he seeks to research the impact of and methods to mitigate the effects of bleeding and the resulting inflammation from device implantation in the CNS. The proposed research plan focuses on advancing one such technology, intracortical microelectrodes for brain-computer interface (BCI) controlled prostheses, which are particularly sensitive to inflammation. The project seeks to mitigate the inflammatory response to enable long-term use of BCI microelectrodes to restore functional limb movement and improve quality of life for paralyzed Veterans.