Bioelektronické materiály a systémy

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Chronic electrical stimulation of peripheral nerves via deep-red light transduced by an implanted organic photocapacitor
(Springer Nature, 2021-11-22) Ejneby, Malin Silver; Jakešová, Marie; Ferrero, Jose J.; Migliaccio, Ludovico; Sahalianov, Ihor; Zhao, Zifang; Berggren, Magnus; Khodagholy, Dion; Derek, Vedran; Gelinas, Jennifer N.; Glowacki, Eric Daniel
Implantable devices for the wireless modulation of neural tissue need to be designed for reliability, safety and reduced invasiveness. Here we report chronic electrical stimulation of the sciatic nerve in rats by an implanted organic electrolytic photocapacitor that transduces deep-red light into electrical signals. The photocapacitor relies on commercially available semiconducting non-toxic pigments and is integrated in a conformable 0.1-mm(3) thin-film cuff. In freely moving rats, fixation of the cuff around the sciatic nerve, 10 mm below the surface of the skin, allowed stimulation (via 50-1,000-mu s pulses of deep-red light at wavelengths of 638 nm or 660 nm) of the nerve for over 100 days. The robustness, biocompatibility, low volume and high-performance characteristics of organic electrolytic photocapacitors may facilitate the wireless chronic stimulation of peripheral nerves. An organic electrolytic photocapacitor transducing deep-red light into electrical signals and implanted within a thin cuff around the sciatic nerve of rats allows for wireless electrical stimulation of the nerve for over 100 days.
Faradaic Pixels for Precise Hydrogen Peroxide Delivery to Control M-Type Voltage-Gated Potassium Channels
(Wiley, 2022-01-01) Abudllaeva, Oliya S.; Sahalianov, Ihor; Ejneby, Malin Silver; Jakešová, Marie; Zozoulenko, Igor; Liin, Sara I.; Glowacki, Eric Daniel
H2O2 plays a significant role in a range of physiological processes where it performs vital tasks in redox signaling. The sensitivity of many biological pathways to H2O2 opens up a unique direction in the development of bioelectronics devices to control levels of reactive-oxygen species (ROS). Here a microfabricated ROS modulation device that relies on controlled faradaic reactions is presented. A concentric pixel arrangement of a peroxide-evolving cathode surrounded by an anode ring which decomposes the peroxide, resulting in localized peroxide delivery is reported. The conducting polymer (poly(3,4-ethylenedioxythiophene) (PEDOT), is exploited as the cathode. PEDOT selectively catalyzes the oxygen reduction reaction resulting in the production of hydrogen peroxide (H2O2). Using electrochemical and optical assays, combined with modeling, the performance of the devices is benchmarked. The concentric pixels generate tunable gradients of peroxide and oxygen concentrations. The faradaic devices are prototyped by modulating human H2O2-sensitive Kv7.2/7.3 (M-type) channels expressed in a single-cell model (Xenopus laevis oocytes). The Kv7 ion channel family is responsible for regulating neuronal excitability in the heart, brain, and smooth muscles, making it an ideal platform for faradaic ROS stimulation. The results demonstrate the potential of PEDOT to act as an H2O2 delivery system, paving the way to ROS-based organic bioelectronics.
Light-Controlled Electric Stimulation with Organic Electrolytic Photocapacitors Achieves Complex Neuronal Network Activation: Semi-Chronic Study in Cortical Cell Culture and Rat Model
(Wiley, 2024-08-13) Nowakowska, Marta; Jakešová, Marie; Schmidt, Tony; Opančar, Aleksandar; Polz, Mathias; Reimer, Robert; Fuchs, Julia; Patz, Silke; Ziesel, Daniel; Scheruebel, Susanne; Kornmueller, Karin; Rienmüller, Theresa; Derek, Vedran; Glowacki, Eric Daniel; Schindl, Rainer; Üçal, Muammer
Neurostimulation employing photoactive organic semiconductors offers an appealing alternative to conventional techniques, enabling targeted action and wireless control through light. In this study, organic electrolytic photocapacitors (OEPC) are employed to investigate the effects of light-controlled electric stimulation on neuronal networks in vitro and in vivo. The interactions between the devices and biological systems are characterized. Stimulation of primary rat cortical neurons results in an elevated expression of c-Fos within a mature neuronal network. OEPC implantation for three weeks and subsequent stimulation of the somatosensory cortex leads to an increase of c-Fos in neurons at the stimulation site and in connected brain regions (entorhinal cortex, hippocampus), both in the ipsi- and contralateral hemispheres. Reactivity of glial and immune cells after semi-chronic implantation of OEPC in the rat brain is comparable to that of surgical controls, indicating minimal foreign body response. Device functionality is further substantiated through retained charging dynamics following explantation. OEPC-based, light-controlled electric stimulation has a significant impact on neural responsiveness. The absence of detrimental effects on both the brain and device encourages further use of OEPC as cortical implants. These findings highlight its potential as a novel mode of neurostimulation and instigate further exploration into applications in fundamental neuroscience. Wireless cortical stimulation is an attractive alternative to standard neurostimulation methods. Organic photoactive semiconductors can transduce light into electric signal, even in ultrathin layers, which can be used to stimulate neurons. In this study, light-based stimulation activated complex neuronal networks in vitro and in vivo, including deep brain regions. The devices proved safe and stable over three weeks of implantation. image
In Vivo Organic Bioelectronics for Neuromodulation
(American Chemical Society, 2022-02-23) Berggren, Magnus; Glowacki, Eric Daniel; Simon, Daniel T.; Stavrinidiou, Eleni; Tybrandt, Klas
The nervous system poses a grand challenge for integration with modern electronics and the subsequent advances in neurobiology, neuroprosthetics, and therapy which would become possible upon such integration. Due to its extreme complexity, multifaceted signaling pathways, and similar to 1 kHz operating frequency, modern complementary metal oxide semiconductor (CMOS) based electronics appear to be the only technology platform at hand for such integration. However, conventional CMOS-based electronics rely exclusively on electronic signaling and therefore require an additional technology platform to translate electronic signals into the language of neurobiology. Organic electronics are just such a technology platform, capable of converting electronic addressing into a variety of signals matching the endogenous signaling of the nervous system while simultaneously possessing favorable material similarities with nervous tissue. In this review, we introduce a variety of organic material platforms and signaling modalities specifically designed for this role as "translator" , focusing especially on recent implementation in in vivo neuromodulation. We hope that this review serves both as an informational resource and as an encouragement and challenge to the field.
Shattering the Water Window: Comprehensive Mapping of Faradaic Reactions on Bioelectronics Electrodes
(AMER CHEMICAL SOC, 2024-10-01) Ehlich, Jiří; Vašíček, Čeněk; Dobeš, Jan; Ruggiero, Amedeo; Vejvodová, Markéta; Glowacki, Eric Daniel
It is generally accepted that for safe use of neural interface electrodes, irreversible faradaic reactions should be avoided in favor of capacitive charge injection. However, in some cases, faradaic reactions can be desirable for controlling specific (electro)physiological outcomes or for biosensing purposes. This study aims to systematically map the basic faradaic reactions occurring at bioelectronic electrode interfaces. We analyze archetypical platinum-iridium (PtIr), the most commonly used electrode material in biomedical implants. By providing a detailed guide to these reactions and the factors that influence them, we offer a valuable resource for researchers seeking to suppress or exploit faradaic reactions in various electrode materials. We employed a combination of electrochemical techniques and direct quantification methods, including amperometric, potentiometric, and spectrophotometric assays, to measure O-2, H-2, pH, H2O2, Cl-2/OCl-, and soluble platinum and iridium ions. We compared phosphate-buffered saline (PBS) with an unbuffered electrolyte and complex cell culture media containing proteins. Our results reveal that the "water window" the potential range without significant water electrolysis varies depending on the electrolyte used. In the culture medium that is rich with redox-active species, a window of potentials where no faradaic process occurs essentially does not exist. Under cathodic polarizations, significant pH increases (alkalization) were observed, while anodic water splitting competes with other processes in media, preventing prevalent acidification. We quantified the oxygen reduction reaction and accumulation of H2O2 as a byproduct. PtIr efficiently deoxygenates the electrolyte under low cathodic polarizations, generating local hypoxia. Under anodic polarizations, chloride oxidation competes with oxygen evolution, producing relatively high and cytotoxic concentrations of hypochlorite (OCl-) under certain conditions. These oxidative processes occur alongside PtIr dissolution through the formation of soluble salts. Our findings indicate that the conventional understanding of the water window is an oversimplification. Important faradaic reactions, such as oxygen reduction and chloride oxidation, occur within or near the edges of the water window. Furthermore, the definition of the water window significantly depends on the electrolyte composition, with PBS yielding different results compared with culture media.

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