Dhawan, Vaishnavi
(2025)
Strategies for Enhancing the Biocompatibility and Chronic Recording Performance of
Neural Interface Devices.
Doctoral Dissertation, University of Pittsburgh.
(Unpublished)
Abstract
Invasive neural microelectrode arrays (MEAs) enable high-resolution bidirectional
communication with nervous tissue and can record neural activity with high spatial selectivity and
resolution. However, their long-term efficacy is hindered by inflammatory responses to
implantation. This dissertation investigates strategies to enhance the biocompatibility and chronic
recording performance of implantable MEAs.
In the first part of this dissertation, we explored the novel application of a chondroitin
sulfate bioactive coating for MEAs. Both in vitro and in vivo studies demonstrated the coating’s
stability, anti-fouling properties, and ability to promote neurite growth and reduce microglial
activation. Single-unit neural recordings and endpoint histology revealed improved recording
performance and reduced inflammation in animals implanted with coated MEAs compared to the
control, showcasing the effectiveness of the coating at acute time points.
In the second part, we examined the impact of MEA substrate rigidity on chronic neural
recording quality and inflammatory tissue response. We compared the performance of stiff silicon-
based and flexible polyimide-based MEAs with similar geometries in the mouse striatum. Flexible
MEAs maintained more stable impedance, noise, peak-to-peak amplitude, and signal-to-noise ratio
(SNR), whereas stiff MEAs showed a progressive decline in recording performance. Compared to
the stiff probes, a milder immune response, and an elevated neural population were observed
around the flexible probes. Increased expression of the mechanosensitive ion channel
correlated with microglial activation and astrocytic reactivity near the stiff probes, suggesting the
involvement of mechanosensitive channels in the tissue response.
Finally, as the first step to investigate bipolar disorder using neural interface devices, we
characterized the neural recording performance of implanted MEAs in the striatum of the bipolar
mania ClockΔ19 mutant mice. We compared the chronic neural recording metrics and histological
markers to wild-type control mice. SNR and channel yield were comparable between the groups,
however, mutant mice exhibited lower impedance, noise levels, and amplitude. A significantly
reduced neuronal population was observed around the implant in mutant mice accompanied by
lower microglia and astrocytic responses, indicating a compromised inflammatory system likely
due to the ClockΔ19 mutation.
These studies collectively contribute to understanding the neural electrode-tissue interface
and present promising strategies for improvement.
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Details
| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
|
| ETD Committee: |
|
| Date: |
7 January 2025 |
| Date Type: |
Publication |
| Defense Date: |
23 August 2024 |
| Approval Date: |
7 January 2025 |
| Submission Date: |
8 October 2024 |
| Access Restriction: |
2 year -- Restrict access to University of Pittsburgh for a period of 2 years. |
| Number of Pages: |
169 |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
Swanson School of Engineering > Bioengineering |
| Degree: |
PhD - Doctor of Philosophy |
| Thesis Type: |
Doctoral Dissertation |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
Neural interface, biocompatibility, neural recording, inflammation |
| Date Deposited: |
07 Jan 2025 21:03 |
| Last Modified: |
07 Jan 2025 21:03 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/47000 |
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