Ph.D. Dissertation Defense
Virtual Zoom Link:
https://cwru.zoom.us/j/91640836146?pwd=sXQgA7ZUYg32mn69or27G6xc7xVxyw.1
11:00 AM, Nord 356
Monday, February 10, 2025
“The use of platelet inspired nanoparticles to reduce neuroinflammation and blood-brain barrier permeability surrounding intracortical microelectrodes”
by
Dhariyat Menendez-Lustri
Ph.D. Candidate
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Department of Biomedical Engineering
Cleveland, OH
Thesis Advisor: Andrew Shoffstall, PhD
ABSTRACT
Brain-computer interfaces (BCIs) bridge the gap between dysfunctional central nervous system circuitry and prosthetic devices for individuals with somatic function loss. Intracortical microelectrodes (IMEs) record action potentials and transmit signals through BCI systems to enable external device functionality for neurorehabilitation. Although neural interfaces address the clinical need for restoring neurological function, IMEs face significant biological challenges. The initial rupturing of the blood-brain barrier (BBB) and chronic neuroinflammatory response can lead to IME failure. One strategy to mitigate biological response involves using anti-inflammatory drugs like dexamethasone (DEX), which suppress pro-inflammatory genes. However, systemically administered pharmaceuticals lack targeting functionality, limiting their therapeutic potential.
This dissertation explores improving IME longevity by mitigating neuroinflammation and resealing the BBB with a drug-loaded bio-inspired nanoparticle. Our approach employs synthetic platelet-inspired nanoparticles (PINs or SPINs) designed to leverage platelet physiology for vascular wound healing. Using IHC, we evaluated SPINs’ ability to target IME sites, reduce BBB permeability, and decrease the presence of activated glial cells. Within the next chapter, we conducted the first omics analysis of SPINs as a drug delivery vehicle for DEX to target chronic inflammation at IME sites. This analysis revealed that encapsulating DEX alters its biodistribution, providing insights not observed with IHC. Multiple doses of DEX-loaded SPINs (SPIN-DEX) demonstrated potential to extend IME longevity by modulating gene expression to reduce neuroinflammation and promote BBB healing. Nanoparticle-based therapies enable adaptable dosing that can be informed by transcriptomic data, offering a promising solution for enhancing IME performance. By addressing chronic inflammation and BBB repair, SPIN-DEX provides a comprehensive approach to overcoming IME-associated biological challenges. These findings highlight the potential of nanoparticle-based drug delivery to improve neural interface performance,