Optimizing the performance of neural interface devices with hybrid poly(3,4-ethylene dioxythiophene) (PEDOT)

Date
2017
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University of Delaware
Abstract
This thesis describes methods for improving the performance of poly(3,4- ethylenedioxythiophene) (PEDOT) as a direct neural interfacing material. The chronic foreign body response is always a challenge for implanted bionic devices. After longterm implantation (typically 2-4 weeks), insulating glial scars form around the devices, inhibiting signal transmission, which ultimately leads to device failure. The mechanical mismatch at the device-tissue interface is one of the issues that has been associated with chronic foreign body response. Another challenge for using PEDOT as a neural interface material is its mechanical failure after implantation. We observed cracking and delamination of PEDOT coatings on devices after extended implantations. ☐ In the first part of this thesis, we present a novel method for directly measuring the mechanical properties of a PEDOT thin film. Before investigating methods to improve the mechanical behavior of PEDOT, a comprehensive understanding of the mechanical properties of PEDOT thin film is required. A PEDOT thin film was machined into a dog-bone shape specimen with a dual beam FIB-SEM. With an OmniProbe, this PEDOT specimen could be attached onto a force sensor, while the other side was attached to OmniProbe. By moving the OmniProbe, the specimen could be deformed in tension, and a force sensor recorded the applied load on the sample simultaneously. Mechanical tensile tests were conducted in the FIB-SEM chamber along with in situ observation. With precise force measurement from the force sensor and the corresponding high resolution SEM images, we were able to convert the data to a stress-strain curve for further analysis. By analyzing these stress-strain curves, we were able to obtain information about PEDOT including the Young’s modulus, strength of failure, strain to failure, and toughness (energy to failure). This information should be useful for future material selection and molecular design for specific applications. ☐ The second section of this thesis is mainly focused on developing a soft and conductive material by in situ PEDOT polymerization into soft matrix. First, PEDOT was in situ polymerized into extracellular matrix (ECM) as a conductive, soft, and bioactive material for neural interfacing. ECM is basically a matrix of proteins which provides biological cues with the potential to promote neural attachment. We modified the electrode to a needle shape, which could be inserted into the ECM film. The limited surface area on the electrode and the close contact with ECM made it possible to polymerize PEDOT into the ECM more easily. The conductivity of PEDOT-ECM was confirmed to be similar to intrinsic PEDOT. A cell adhesion test using the PC12 cell line was used to evaluate its biocompatibility. PEDOT-ECM shows improved cell adhesion for PC12 cells, as compared either bare metal electrodes or PEDOT coated surfaces. In the future this approach may be elevated to an “ autologous” concept, where the ECM could be derived from the host patients themselves to further reduce the foreign body response. ☐ Second, low modulus hydrogels were used as templates for PEDOT polymerization. EDOT monomers were premixed into agarose hydrogels. The electrochemical polymerization was typically conducted in potentiostatic (constant voltage) mode with working voltage of 2 V. After 0.8 C/cm2 charge density, a significant dark blue cloud was observed indicating that PEDOT was in situ polymerized into hydrogel matrix. A series of studies was conducted to confirm the improved mechanical properties, electrical properties and biocompatibility of the PEDOT-gel as compared to the typical solid PEDOT. Animal studies were conducted to evaluate the performance of PEDOT-gel coated electrode in vivo. Rats were used as the animal model with 3 rats in each group of bare electrode, PEDOT-coated, and PEDOT-gel coated electrode (n=9). The in vivo impedance was used to confirm the performance of the implanted electrodes. The results showed that the impedance had a significant increase after 4 weeks with the bare and solid PEDOT-coated electrode. This is consistent with the typical glial scar encapsulation around the electrode leading to an impedance increase. PEDOT-gel presents consistently low impedance along with 10 weeks implantation implying there was much less reactive response around the insertion site. These in vivo experiments on PEDOT-gels suggest that PEDOT-gels are promising neural interfacing materials for patients clinically.
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