Transient electronics for edible neuroprosthetics

Transient electronics is a recent challenging research field aiming at the realization of functional electronic devices able to disappear in a controlled and predefined manner. Amongst different applications, biomedical devices based on transient technology have raised a lot of interest. Their ability to dissolve within the biological environment, thus avoiding infections due to a prolonged stay and risks related to surgical retrieval, is their main appealing characteristic. In many cases the device relies on silicon-based electronics, but the incorporation of polymers in the design, mostly as flexible substrate or for drug-release purposes, is becoming more and more exploited. Due to the intrinsic versatility of polymeric materials, which potentially allow for a great variety of customized application and fabrication techniques, fully polymer-based transient electronic devices represent the natural step forward in this research area. We therefore intend to contribute to the progress in the field of transient electronics by fabricating probes for neural signal recording based on biocompatible and biodegradable polymers, both as substrate and active material, thus introducing the edible neuroprosthetics concept. In the specific case, we relied on Polycaprolactone (PCL) or Poly Lactic-co-Glycolic Acid (PLGA) as substrate and Poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) (Pedot:PSS) as conductive conjugated polymer. With these materials as building blocks, a series of passive neural probes were fabricated and implanted in mice brains (visual cortex area) to assess their in-vivo durability. Several time-points (1, 3, 6 and 9 months) have been established for the implants analysis in order to have a better comprehension of the degradation process within the biological environment and the response of the biological environment itself to the insertion of an external object. Preliminary results show that after one month of implantation the astrocytes are visibly activated as expected, whereas there is no evidence of activated microglia. In the near future, implantation of active neural probes will give insight also on the recording capacity of the devices

Multilayer 3D electrodes for neural implants

Objective. In many applications, multielectrode arrays employed as neural implants require a high density and a high number of electrodes to precisely record and stimulate the activity of the nervous system while preserving the overall size of the array as little as possible. Approach. Here we present a multilayer and three-dimensional (3D) electrode array, together with its manufacturing method, enabling a higher electrode density and a more efficient signal transduction with the biological tissue. Main results. The 3D structure of the electrode array allows a multilayer placement of the interconnects within a flexible substrate, it narrows the probe size per the same number of electrodes, and it maintains the electrode contacts at the same level within the tissue. In addition, it augments the electrode surface area, leading to a lower electrochemical impedance and a higher charge storage capacity. To characterize the recordings capabilities of the multilayer 3D electrodes, we measured visually evoked cortical potentials in mice and analysed the evolution of the peak prominences and latencies according to different light intensities and recording depths within the brain. The resulting signal-to-noise ratio is improved compared to flat electrodes. Finally, the 3D electrodes have been imaged inside a clarified mouse brain using a light-sheet microscope to visualize their integrity within the tissue. Significance. The multilayer 3D electrodes have proved to be a valid technology to ensure tissue proximity and higher recording/stimulating efficiencies while enabling higher electrode density and reducing the probe size

Design and validation of a foldable and photovoltaic wide-field epiretinal prosthesis

Retinal prostheses have been developed to fight blindness in people affected by outer retinal layer dystrophies. To date, few hundred patients have received a retinal implant. Inspired by intraocular lenses, we have designed a foldable and photovoltaic wide-field epiretinal prosthesis (named POLYRETINA) capable of stimulating wireless retinal ganglion cells. Here we show that within a visual angle of 46.3 degrees, POLYRETINA embeds 2215 stimulating pixels, of which 967 are in the central area of 5 mm, it is foldable to allow implantation through a small scleral incision, and it has a hemispherical shape to match the curvature of the eye. We demonstrate that it is not cytotoxic and respects optical and thermal safety standards; accelerated ageing shows a lifetime of at least 2 years. POLYRETINA represents significant progress towards the improvement of both visual acuity and visual field with the same device, a current challenging issue in the field

Development and Characterization of PEDOT:PSS/Alginate Soft Microelectrodes for Application in Neuroprosthetics

Reducing the mechanical mismatch between the stiffness of a neural implant and the softness of the neural tissue is still an open challenge in neuroprosthetics. The emergence of conductive hydrogels in the last few years has considerably widened the spectrum of possibilities to tackle this issue. Nevertheless, despite the advancements in this field, further improvements in the fabrication of conductive hydrogel-based electrodes are still required. In this work, we report the fabrication of a conductive hydrogel-based microelectrode array for neural recording using a hybrid material composed of poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate), and alginate. The mechanical properties of the conductive hydrogel have been investigated using imaging techniques, while the electrode arrays have been electrochemically characterized at each fabrication step, and successfully validated both in vitro and in vivo. The presence of the conductive hydrogel, selectively electrodeposited onto the platinum microelectrodes, allowed achieving superior electrochemical characteristics, leading to a lower electrical noise during recordings. These findings represent an advancement in the design of soft conductive electrodes for neuroprosthetic applications

Information and communication technologies-based interventions for children with autism spectrum conditions: a systematic review of randomized control trials from a positive technology perspective

Information and communication technologies (ICTs) have become more widely used in the past years to help people with autism spectrum conditions (ASC). Serious games embedded into computers or tablets, as well as social robots, are the most employed ICT-related tools that are appealing to and appropriate for autistic children. The goal of ICT applications is to enhance behavioral abnormalities associated with ASC while also creating an interactive link between one person and one computer. Comparatively, to human-based therapy, ICT tools aid to inspire autistic children by providing predictability and regularity of tasks. Regaining social skills is the primary behavioral goal for which ICT tools have been designed and implemented. In the past several years, many studies have been created to show how effective it is at improving targeted behaviors. However, only a small number of researchers have used an RCT approach to evaluate its effectiveness. In this systematic review, we only included RCT studies where ICT technologies were used to help children with ASC in improving their social skills. Only 14 RCT studies satisfied the criteria and 12 described significant improvements, showing how the use of technology in educational contexts produced better improvement in developing several social skill facets with respect to the traditional face-to-face approach. Some studies used interventions and outcome measures focused on the core ASC symptoms, but many others addressed neurocognitive functions directly, like social cognition or emotional regulation, while other more general functions such as language or adaptive behaviors. We propose a classification based on processes and outcome measures to foster future research in this specific area of research. The behavioral intervention mediated by technological tools such as computer-based, tablet, and social robotics, undoubtedly provides a comfortable environment that promotes constant learning for people with ASC. Evidence provided in this review highlights the translational potential of this field of study in primary care practice and educational settings

Mindfulness-Based Interventions for Physical and Psychological Wellbeing in Cardiovascular Diseases: A Systematic Review and Meta-Analysis

Background: Recently, there has been an increased interest in the efficacy of mindfulness-based interventions (MBI) for people with cardiovascular diseases (CVD), although the exact beneficial effects remain unclear. Methods: This review aims to establish the role of MBI in the management of wellbeing for patients with CVD. Seventeen articles have been included in this systematic synthesis of the literature and eleven in the meta-analysis. Results: Considering physical (i.e., heart rate, blood pressure) and psychological outcomes (i.e., depression, anxiety, stress, styles of coping), the vast majority of studies confirmed that MBI has a positive influence on coping with psychological risk factors, also improving physiological fitness. Random-effects meta-analysis models suggested a moderate-to-large effect size in reducing anxiety, depression, stress, and systolic blood pressure. Conclusions: Although a high heterogeneity was observed in the methodological approaches, scientific literature confirmed that MBI can now be translated into a first-line intervention tool for improving physical and psychological wellbeing in CVD patients

Epistolari dal Due al Seicento. Modelli, questioni ecdotiche, edizioni, cantieri aperti (Gargnano del Garda, 29 settembre - 1° ottobre 2014)

Nei secoli passati, la lettera era l'unico mezzo di comunicazione: familiare, amichevole, d'ufficio o di servizio, ma anche strumento di dibattito politico e culturale. Lo studio degli epistolari dei singoli ma anche delle reti di comunicazione e di scambio è uno dei grandi temi della ricerca europea contemporanea. Vi si inserisce questo secondo volume dei "Quaderni di Gargnano", che - volgendosi sia alla produzione latina sia a quella volgare dal Due al Seicento - si sofferma su problemi metodologici e casi significativi, con impostazioni e tagli diversi: dall'ecdotica alla filologia, dall'archivistica, alla storia, alla storia delle discipline

In vivo evaluation of gene editing and prosthetic strategies to restore vision in small and large animal models of retinal degeneration

Inherited retinal diseases (IRDs) form a group of diverse disorders that lead to the degeneration of the light-sensing cells of the retina: the photoreceptors. IRDs are among the leading causes of blindness in working-age adults living in industrialized countries and their treatment has been a long-term challenge in medicine. Given the heterogeneity of IRDs in terms of causative genes and symptoms, finding a common therapy is not a real possibility. Conversely, it is important to research as many different approaches as possible so as to have the opportunity to decide which one to use for a specific patient. The outcome of clinical interventions depends in large part on the preclinical research conducted on animal models. As an example of this, this thesis illustrates two preclinical approaches to the treatment of retinal degenerations that lie at the opposite ends of the spectrum of available therapies. The first approach discussed is gene editing. This strategy is most effective during the development of the retina and can be used to correct genetic mutations causing the degeneration of photoreceptors on the progenitor cells. Here, we used a tailored gene editing system based on clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) to prevent photoreceptor death in the retinal degeneration 10 (Rd10) mouse model of retinitis pigmentosa. The construct was delivered in the photoreceptor cells by electroporation and targets the mutated gene, editing its sequence with the help of a DNA repair template. This technique for gene editing has shown promising results in terms of visual function preservation in mice, inspiring further research into viral-free gene editing approaches. On the opposite side of the range of therapeutic options, prosthetic devices are generally used for late-stage retinal degeneration since they bypass the photoreceptor layer and rely on the retinal internal circuits to perform visual stimulation. In this work, I describe a series of experiments performed to test the POLYRETINA photovoltaic epiretinal visual prosthesis, previously developed by our laboratory, in a minipig model of chemically induced retinal degeneration. First, the visual responses were carefully characterized in the animal model before and after the injection of the toxin. Then, preliminary results were obtained using the prosthesis to stimulate the blind retina. Although the experiments are still ongoing, the results are encouraging and demonstrate that we could indeed use a completely photovoltaic prosthesis to restore visual perception in blind patients. In conclusion, this thesis displays preclinical research concerning two ways to restore vision, each adapted to a different stage of retinal degeneration. The overarching goal is to improve as much as possible the outcome of the therapy for the benefit of blind patients. To this end, we need to continue to test all the approaches that have so far shown promising results, such as the ones presented herein, while continuing to develop new ones. This outlook, implemented at the preclinical level, can lead to the best chances of a successful clinical intervention. At the same time, the diagnostic tools need to be perfected and precisely utilized to determine which therapeutic option is best suited for a specific patient