Reactive-Accelerated-Aging Testing of Thinned Tissue-Engineered Electronic Nerve Interfaces.

Tissue responses can cause a significant reduction in the performance of microelectrode-based devices implanted into neural tissue. Since the reduction of the thickness of implants has been shown to reduce tissue response, in this work we report on our effects to reduce the thickness of our tissue-engineered-electronic-nerve-interface (TEENI) devices and characterize their long-term reliability in a harsh environment. We were able to reduce the thickness of the TEENI threads that are to be located in nerve tissue from ~10 µm to ~2.5 µm in total thickness. To maintain the handleability needed during the assembly of the TEENI device into the hydrogel-based scaffold, we maintained full thickness elsewhere in the TEENI device and added support rails. During longitudinal reactive-accelerated-aging (RAA) experiments performed over 6 days and at 67°C, which corresponds to ~48 days in tissue, we observed that some channels maintain a stable impedance and others do not. Although analyses performed using a scanning electron microscope could clearly reveal delamination in some channels that exhibited large changes in impedance, it did not always correlate. Some channels with significant changes in impedance did not exhibit any observable delamination. Additional work is needed to study the relationship between changes in impedance and structural changes in the device, with the goal of improving device design to achieve longer-lasting devices.

Examining thein vivofunctionality of the magnetically aligned regenerative tissue-engineered electronic nerve interface (MARTEENI).

Objective. Although neural-enabled prostheses have been used to restore some lost functionality in clinical trials, they have faced difficulty in achieving high degree of freedom, natural use compared to healthy limbs. This study investigated thein vivofunctionality of a flexible and scalable regenerative peripheral-nerve interface suspended within a microchannel-embedded, tissue-engineered hydrogel (the magnetically aligned regenerative tissue-engineered electronic nerve interface (MARTEENI)) as a potential approach to improving current issues in peripheral nerve interfaces.Approach. Assembled MARTEENI devices were implanted in the gaps of severed sciatic nerves in Lewis rats. Both acute and chronic electrophysiology were recorded, and channel-isolated activity was examined. In terminal experiments, evoked activity during paw compression and stimulus response curves generated from proximal nerve stimulation were examined. Electrochemical impedance spectroscopy was performed to assess the complex impedance of recording sites during chronic data collection. Features of the foreign-body response (FBR) in non-functional implants were examined using immunohistological methods.Main results. Channel-isolated activity was observed in acute, chronic, and terminal experiments and showed a typically biphasic morphology with peak-to-peak amplitudes varying between 50 and 500µV. For chronic experiments, electrophysiology was observed for 77 days post-implant. Within the templated hydrogel, regenerating axons formed minifascicles that varied in both size and axon count and were also found to surround device threads. No axons were found to penetrate the FBR. Together these results suggest the MARTEENI is a promising approach for interfacing with peripheral nerves.Significance. Findings demonstrate a high likelihood that observed electrophysiological activity recorded from implanted MARTEENIs originated from neural tissue. The variation in minifascicle size seen histologically suggests that amplitude distributions observed in functional MARTEENIs may be due to a combination of individual axon and mini-compound action potentials. This study provided an assessment of a functional MARTEENI in anin vivoanimal model for the first time.