woeppel, kevin
(2022)
Nanoparticle Mediated Strategies Towards Stable Neural Electrode Tissue Interfaces.
Doctoral Dissertation, University of Pittsburgh.
(Unpublished)
This is the latest version of this item.
Abstract
Interfacing with electrically excitable tissues via electronic devices has unlocked countless therapies and scientific discoveries, but the chronic stability and long-term clinical viability of these devices is greatly limited by the host tissues response to the implant. For example, chronic neural recording devices experience low recording yield, signal drift and degradation over time as the host inflammatory responses cause neuronal death and degeneration, microglia activation, scar tissue formation, and electrode material degradation. Previous research efforts have shown promising results from protein based biomimetic coating and conducting polymer-based drug release coatings in mitigating these adverse tissue responses. In this dissertation, we have utilized silica nanoparticles (SNP) to greatly enhance the efficacy of these coatings in different manners. The first is to enhance protein surface immobilization by the pre-deposition of a nanotopographical coating of silica nanoparticles. This nanotopographical coating elevated the protein binding, bioactivity, and stability, enhancing the tissue integration and long-term recording performance of neural electrodes. Further, the nanotopographical coating enabled the drying and storage of the biofunctionalized electrodes without loss of bioactivities, allowing for practical distribution of the protein modified devices to users. The second strategy is a novel mesoporous silica nanoparticle dopant for conducting polymers. These mesoporous particles can be loaded with pharmaceuticals and then used as drug carriers to bring the compounds into electropolymerized conducting polymer polyethylenedioxythiophene (PEDOT) coating. The resulting PEDOT/SNP films were able to increase drug release by a factor of 16 compared to traditional conducting polymer-based drug delivery systems and enabled the loading and delivery of positively charge and electroactive compounds, as well as the co-loading and release of multiple compounds from the same film. In vivo, we demonstrate that the bioactivity of the released compounds is maintained by temporally modulating neural activity and vascular dynamics. We may make use of in vivo drug delivery to reduce the effects of injury driven excitotoxicity which are observed following implantation or to expediate re-perfusion of the tissues around the electrode after injury induced damage to cortical vasculature.
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Details
| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
|
| ETD Committee: |
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| Date: |
10 June 2022 |
| Date Type: |
Publication |
| Defense Date: |
25 March 2022 |
| Approval Date: |
10 June 2022 |
| Submission Date: |
4 April 2022 |
| Access Restriction: |
1 year -- Restrict access to University of Pittsburgh for a period of 1 year. |
| Number of Pages: |
257 |
| 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: |
Neuroengineering |
| Date Deposited: |
10 Jun 2023 05:00 |
| Last Modified: |
10 Jun 2023 05:15 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/42586 |
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