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Many biological processes rely on endogenous electric fields (EFs), including tissue regeneration, cell development, wound healing, and cancer metastasis. Mimicking these biological EFs by applying external direct current stimulation (DCS) is therefore the key to many new therapeutic strategies. During DCS, the charge transfer from electrode to tissue relies on a combination of reversible and irreversible electrochemical processes, which may generate toxic or bio-altering substances, including metal ions and reactive oxygen species (ROS). Poly(3,4-ethylenedioxythiophene) (PEDOT) based electrodes are emerging as suitable candidates for DCS to improve biocompatibility compared to metals. This work addresses whether PEDOT electrodes can be tailored to favor reversible biocompatible charge transfer. To this end, different PEDOT formulations and their respective back electrodes are studied using cyclic voltammetry, chronopotentiometry, and direct measurements of H2O2 and O2. This combination of electrochemical methods sheds light on the time dynamics of reversible and irreversible charge transfer and the relationship between capacitance and ROS generation. The results presented here show that although all electrode materials investigated generate ROS, the onset of ROS can be delayed by increasing the electrode's capacitance via PEDOT coating, which has implications for future bioelectronic devices that allow longer reversibly driven pulse durations during DCS., Validerad;2024;Nivå 2;2024-08-01 (signyg);Funder: SPEEDER (101113487); Health Research Council of New Zealand (HRC/Catwalk Partnership 19/895);Full text license: CC BY

Assessing historical environmental conditions linked to habitat colonization is important for understanding long-term resilience and improving conservation and restoration efforts. Such information is lacking for the seagrass Zostera marina, an important foundation species across cold-temperate coastal areas of the Northern Hemisphere. Here, we reconstructed environmental conditions during the last 14,000 years from sediment cores in two eelgrass (Z. marina) meadows along the Swedish west coast, with the main aims to identify the time frame of seagrass colonization and describe subsequent biogeochemical changes following establishment. Based on vegetation proxies (lipid biomarkers), eelgrass colonization occurred about 2,000 years ago after geomorphological changes that resulted in a shallow, sheltered environment favoring seagrass growth. Seagrass establishment led to up to 20- and 24-fold increases in sedimentary carbon and nitrogen accumulation rates, respectively. This demonstrates the capacity of seagrasses as efficient ecosystem engineers and their role in global change mitigation and adaptation through CO2 removal, and nutrient and sediment retention. By combining regional climate projections and landscape models, we assessed potential climate change effects on seagrass growth, productivity and distribution until 2100. These predictions showed that seagrass meadows are mostly at risk from increased sedimentation and hydrodynamic changes, while the impact from sea level rise alone might be of less importance in the studied area. This study showcases the positive feedback between seagrass colonization and environmental conditions, which holds promise for successful conservation and restoration efforts aimed at supporting climate change mitigation and adaptation, and the provision of several other crucial ecosystem services.

Electrical stimulation (ES) shows promise as a therapy to promote recovery and regeneration after spinal cord injury. ES therapy establishes beneficial electric fields (EFs) and has been investigated in numerous studies, which date back nearly a century. In this review, we discuss the various engineering approaches available to generate regenerative EFs through direct current electrical stimulation and very low frequency electrical stimulation. We highlight the electrode-tissue interface, which is important for the appropriate choice of electrode material and stimulator circuitry. We discuss how to best estimate and control the generated field, which is an important measure for comparability of studies. Finally, we assess the methods used in these studies to measure functional recovery after the injury and treatment. This work reviews studies in the field of ES therapy with the goal of supporting decisions regarding best stimulation strategy and recovery assessment for future work., Validerad;2023;Nivå 2;2023-12-12 (hanlid);Funder: Health Research Council of New Zealand (HRC/Catwalk Partnership 19/895); Neurological Foundation (1952 FF); German Research Foundation (EXC 1086); European Union's Horizon 2020 Research and Innovation program (759655);Full text license: CC BY

Objective. Electrical stimulation of visual cortex via a neuroprosthesis induces the perception of dots of light ('phosphenes'), potentially allowing recognition of simple shapes even after decades of blindness. However, restoration of functional vision requires large numbers of electrodes, and chronic, clinical implantation of intracortical electrodes in the visual cortex has only been achieved using devices of up to 96 channels. We evaluated the efficacy and stability of a 1024-channel neuroprosthesis system in non-human primates (NHPs) over more than 3 years to assess its suitability for long-term vision restoration.Approach. We implanted 16 microelectrode arrays (Utah arrays) consisting of 8 × 8 electrodes with iridium oxide tips in the primary visual cortex (V1) and visual area 4 (V4) of two sighted macaques. We monitored the animals' health and measured electrode impedances and neuronal signal quality by calculating signal-to-noise ratios of visually driven neuronal activity, peak-to-peak voltages of the waveforms of action potentials, and the number of channels with high-amplitude signals. We delivered cortical microstimulation and determined the minimum current that could be perceived, monitoring the number of channels that successfully yielded phosphenes. We also examined the influence of the implant on a visual task after 2-3 years of implantation and determined the integrity of the brain tissue with a histological analysis 3-3.5 years post-implantation.Main results. The monkeys remained healthy throughout the implantation period and the device retained its mechanical integrity and electrical conductivity. However, we observed decreasing signal quality with time, declining numbers of phosphene-evoking electrodes, decreases in electrode impedances, and impaired performance on a visual task at visual field locations corresponding to implanted cortical regions. Current thresholds increased with time in one of the two animals. The histological

Seagrass meadows deliver a range of ecosystem services, where one of the more important is the capacity to store carbon and serve as sinks for atmospheric carbon dioxide. The capacity of seagrass meadows for carbon storage might, however, be modified and complicated by several factors; one important factor is the possible effects of calcification within the meadows. In tropical areas, seagrass meadows can contain high proportions of calcareous organisms, which through their calcification may cause release of CO2. To study this aspect of the CO2 balance within tropical seagrass systems, we investigated the air-water CO2 flux in seagrass mesocosms with different plant community compositions, i.e. mixtures of seagrass and calcifying macroalgae, having similar overall photosynthetic oxygen evolution rates. The measured CO2 fluxes changed both in rate and direction over the day and were significantly related to plant community composition. Downward fluxes of CO2 were found only over vegetation with high proportion of seagrass and in the afternoon, whereas occurrence of calcifying algae appeared to reverse the flow. A partial least squares (PLS) regression model indicated that pH, pCO2 and dissolved inorganic carbon (DIC) were the primary environmental variables predicting the CO2 fluxes. Our findings show that algal calcification might partly counteract the carbon sequestration in seagrass meadows.

The tunable electrical properties of conducting polymers (CPs), their biocompatibility, fabrication versatility, and cost-efficiency make them an ideal coating material for stimulation electrodes in biomedical applications. Several biological processes like wound healing, neuronal regrowth, and cancer metastasis, which rely on constant electric fields, demand electrodes capable of delivering direct current stimulation (DCs) for long times without developing toxic electrochemical reactions. Recently, CPs such as poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT/PSS) have demonstrated outstanding capability for delivering DCs without damaging cells in culture while not requiring intermediate buffers, contrary to the current research setups relying on noble-metals and buffering bridges. However, clear understanding of how electrode design and CP synthesis influence DCs properties of these materials has not been provided until now. This study demonstrates that various PEDOT-based CP coatings and hydrogels on rough electrodes can deliver DCs without substantial changes to the electrode and the noticeable development of chemical by-products depending on the electrode area and polymer thickness. A comprehensive analysis of the tested coatings is provided according to the desired application and available resources, alongside a proposed explanation for the observed electrochemical behavior. The CPs tested herein can pave the way toward the widespread implementation of DCs as a therapeutic stimulation paradigm., Validerad;2023;Nivå 2;2023-04-18 (joosat);Funder: German Research Foundation (DFG, EXC 1086); Freiburg Institute for Advanced Studies FRIASFull text license: CC BY

Upon cutaneous injury, the human body naturally forms an electric field (EF) that acts as a guidance cue for relevant cellular and tissue repair and reorganization. However, the direct current (DC) flow imparted by this EF can be impacted by a variety of diseases. This work delves into the impact of DC stimulation on both healthy and diabetic in vitro wound healing models of human keratinocytes, the most prevalent cell type of the skin. The culmination of non-metal electrode materials and prudent microfluidic design allowed us to create a compact bioelectronic platform to study the effects of different sustained (12 hours galvanostatic DC) EF configurations on wound closure dynamics. Specifically, we compared if electrotactically closing a wound's gap from one wound edge (i.e., uni-directional EF) is as effective as compared to alternatingly polarizing both the wound's edges (i.e., pseudo-converging EF) as both of these spatial stimulation strategies are fundamental to the eventual translational electrode design and strategy. We found that uni-directional electric guidance cues were superior in group keratinocyte healing dynamics by enhancing the wound closure rate nearly three-fold for both healthy and diabetic-like keratinocyte collectives, compared to their non-stimulated respective controls. The motility-inhibited and diabetic-like keratinocytes regained wound closure rates with uni-directional electrical stimulation (increase from 1.0 to 2.8% h−1) comparable to their healthy non-stimulated keratinocyte counterparts (3.5% h−1). Our results bring hope that electrical stimulation delivered in a controlled manner can be a viable pathway to accelerate wound repair, and also by providing a baseline for other researchers trying to find an optimal electrode blueprint for in vivo DC stimulation., Validerad;2023;Nivå 2;2023-04-18 (joosat);Funder: German Research Foundation, DFG ( EXC 1086); Federal Ministry of Economics, Science and Arts of Baden Württemberg; Wissenschaftliche Gesellschaft Freiburg; Deutscher Akademischer AustauschdienstLicens fulltext: CC BY License

Transcranial direct current stimulation (tDCS) is a promising non-invasive brain stimulation method to treat neurological and psychiatric diseases. However, its underlying neural mechanisms warrant further investigation. Indeed, dose–response interrelations are poorly understood. Placing explanted brain tissue, mostly from mice or rats, into a uniform direct current electric field (dcEF) is a well-established in vitro system to elucidate the neural mechanism of tDCS. Nevertheless, we will show that generating a defined, uniform, and constant dcEF throughout a brain slice is challenging. This article critically reviews the methods used to generate and calibrate a uniform dcEF. We use finite element analysis (FEA) to evaluate the widely used parallel electrode configuration and show that it may not reliably generate uniform dcEF within a brain slice inside an open interface or submerged chamber. Moreover, equivalent circuit analysis and measurements inside a testing chamber suggest that calibrating the dcEF intensity with two recording electrodes can inaccurately capture the true EF magnitude in the targeted tissue when specific criteria are not met. Finally, we outline why microfluidic chambers are an effective and calibration-free approach of generating spatiotemporally uniform dcEF for DCS in vitro studies, facilitating accurate and fine-scale dcEF adjustments. We are convinced that improving the precision and addressing the limitations of current experimental platforms will substantially improve the reproducibility of in vitro experimental results. A better mechanistic understanding of dose–response relations will ultimately facilitate more effective non-invasive stimulation therapies in patients., Validerad;2023;Nivå 2;2023-01-17 (sofila);Funder: National Institutes of Health, USA (grant no. 1R01NS109498); Federal Ministry of Education and Research (gtant no. BMBF, 01GQ1804A);Freiburg Institute for Advanced Studies (FRIAS); Brainlinks-BrainTools; German Research Foundation (grant no. EXC 1086); Federal Ministry of Economics, Science and Arts of Baden Württemberg

Flexible implantable neurointerfaces show great promise in addressing one of the major challenges of implantable neurotechnology, namely the loss of signal connected to unfavorable probe tissue interaction. The authors here show how multilayer polyimide probes allow high-density intracortical recordings to be combined with a reliable long-term stable tissue interface, thereby progressing toward chronic stability of implantable neurotechnology. The probes could record 10–60 single units over 5 months with a consistent peak-to-peak voltage at dimensions that ensure robust handling and insulation longevity. Probes that remain in intimate contact with the signaling tissue over months to years are a game changer for neuroscience and, importantly, open up for broader clinical translation of systems relying on neurotechnology to interface the human brain., Validerad;2023;Nivå 2;2023-07-05 (hanlid);Funder: German Research Foundation (DFG, EXC 1086); Freiburg Institute for Advanced Studies (FRIAS)

Seagrass meadows are globally important blue carbon sinks. In northern cold-temperate regions, eelgrass (Zostera marina) is the dominant seagrass species, and although their sedimentary carbon stocks have been quantified across regions, information regarding the CO2 withdrawal capacity as carbon sinks remains scarce. Here we assessed the carbon (Corg) accumulation rates (CARs) and stocks as well as the organic matter sources in five seagrass meadows in the Gullmar Fjord area on the Swedish Skagerrak coast. We found that the mean (±SD) CAR was 14 ± 3 g Corg m-2 yr-1 over the last ~120–140 years (corresponding to a yearly uptake of 52.4 ± 12.6 g CO2 m-2). The carbon sink capacity is in line with other Z. marina areas but relatively low compared to other seagrass species and regions globally. About half of the sedimentary carbon accumulation (7.1 ± 3.3 g Corg m-2 yr-1) originated from macroalgae biomass, which highlights the importance of non-seagrass derived material for the carbon sink function of seagrass meadows in the area. The Corg stocks were similar among sites when comparing at a standardized depth of 50 cm (4.6–5.9 kg Corg m-2), but showed large variation when assessed for the total extent of the cores (ranging from 0.7 to 20.6 kg Corg m-2 for sediment depths of 11 to at least 149 cm). The low sediment accretion rates (1.18–1.86 mm yr-1) and the relatively thick sediment deposits (with a maximum of >150 cm of sediment depth) suggests that the carbon stocks have likely been accumulated for an extended period of time, and that the documented loss of seagrass meadows in the Swedish Skagerrak region and associated erosion of the sediment could potentially have offset centuries of carbon sequestration., Funder:Albert och Maria Bergström foundationBolin Centre for climate research