Regenerative bioelectronics: A strategic roadmap for precision medicine.

In the past few decades, stem cell-based regenerative engineering has demonstrated its significant potential to repair damaged tissues and to restore their functionalities. Despite such advancement in regenerative engineering, the clinical translation remains a major challenge. In the stance of personalized treatment, the recent progress in bioelectronic medicine likewise evolved as another important research domain of larger significance for human healthcare. Over the last several years, our research group has adopted biomaterials-based regenerative engineering strategies using innovative bioelectronic stimulation protocols based on either electric or magnetic stimuli to direct cellular differentiation on engineered biomaterials with a range of elastic stiffness or functional properties (electroactivity/magnetoactivity). In this article, the role of bioelectronics in stem cell-based regenerative engineering has been critically analyzed to stimulate futuristic research in the treatment of degenerative diseases as well as to address some fundamental questions in stem cell biology. Built on the concepts from two independent biomedical research domains (regenerative engineering and bioelectronic medicine), we propose a converging research theme, 'Regenerative Bioelectronics'. Further, a series of recommendations have been put forward to address the current challenges in bridging the gap in stem cell therapy and bioelectronic medicine. Enacting the strategic blueprint of bioelectronic-based regenerative engineering can potentially deliver the unmet clinical needs for treating incurable degenerative diseases.

A universal interface for plug-and-play assembly of stretchable devices.

Stretchable hybrid devices have enabled high-fidelity implantable1-3 and on-skin4-6 monitoring of physiological signals. These devices typically contain soft modules that match the mechanical requirements in humans7,8 and soft robots9,10, rigid modules containing Si-based microelectronics11,12 and protective encapsulation modules13,14. To make such a system mechanically compliant, the interconnects between the modules need to tolerate stress concentration that may limit their stretching and ultimately cause debonding failure15-17. Here, we report a universal interface that can reliably connect soft, rigid and encapsulation modules together to form robust and highly stretchable devices in a plug-and-play manner. The interface, consisting of interpenetrating polymer and metal nanostructures, connects modules by simply pressing without using pastes. Its formation is depicted by a biphasic network growth model. Soft-soft modules joined by this interface achieved 600% and 180% mechanical and electrical stretchability, respectively. Soft and rigid modules can also be electrically connected using the above interface. Encapsulation on soft modules with this interface is strongly adhesive with an interfacial toughness of 0.24 N mm-1. As a proof of concept, we use this interface to assemble stretchable devices for in vivo neuromodulation and on-skin electromyography, with high signal quality and mechanical resistance. We expect such a plug-and-play interface to simplify and accelerate the development of on-skin and implantable stretchable devices.

Imperceptible energy harvesting device and biomedical sensor based on ultraflexible ferroelectric transducers and organic diodes.

Energy autonomy and conformability are essential elements in the next generation of wearable and flexible electronics for healthcare, robotics and cyber-physical systems. This study presents ferroelectric polymer transducers and organic diodes for imperceptible sensing and energy harvesting systems, which are integrated on ultrathin (1-µm) substrates, thus imparting them with excellent flexibility. Simulations show that the sensitivity of ultraflexible ferroelectric polymer transducers is strongly enhanced by using an ultrathin substrate, which allows the mounting on 3D-shaped objects and the stacking in multiple layers. Indeed, ultraflexible ferroelectric polymer transducers have improved sensitivity to strain and pressure, fast response and excellent mechanical stability, thus forming imperceptible wireless e-health patches for precise pulse and blood pressure monitoring. For harvesting biomechanical energy, the transducers are combined with rectifiers based on ultraflexible organic diodes thus comprising an imperceptible, 2.5-µm thin, energy harvesting device with an excellent peak power density of 3 mW·cm-3.

Adaptive self-healing electronic epineurium for chronic bidirectional neural interfaces.

Realizing a clinical-grade electronic medicine for peripheral nerve disorders is challenging owing to the lack of rational material design that mimics the dynamic mechanical nature of peripheral nerves. Electronic medicine should be soft and stretchable, to feasibly allow autonomous mechanical nerve adaptation. Herein, we report a new type of neural interface platform, an adaptive self-healing electronic epineurium (A-SEE), which can form compressive stress-free and strain-insensitive electronics-nerve interfaces and enable facile biofluid-resistant self-locking owing to dynamic stress relaxation and water-proof self-bonding properties of intrinsically stretchable and self-healable insulating/conducting materials, respectively. Specifically, the A-SEE does not need to be sutured or glued when implanted, thereby significantly reducing complexity and the operation time of microneurosurgery. In addition, the autonomous mechanical adaptability of the A-SEE to peripheral nerves can significantly reduce the mechanical mismatch at electronics-nerve interfaces, which minimizes nerve compression-induced immune responses and device failure. Though a small amount of Ag leaked from the A-SEE is observed in vivo (17.03 ppm after 32 weeks of implantation), we successfully achieved a bidirectional neural signal recording and stimulation in a rat sciatic nerve model for 14 weeks. In view of our materials strategy and in vivo feasibility, the mechanically adaptive self-healing neural interface would be considered a new implantable platform for a wide range application of electronic medicine for neurological disorders in the human nervous system.

Locally coupled electromechanical interfaces based on cytoadhesion-inspired hybrids to identify muscular excitation-contraction signatures.

Coupling myoelectric and mechanical signals during voluntary muscle contraction is paramount in human-machine interactions. Spatiotemporal differences in the two signals intrinsically arise from the muscular excitation-contraction process; however, current methods fail to deliver local electromechanical coupling of the process. Here we present the locally coupled electromechanical interface based on a quadra-layered ionotronic hybrid (named as CoupOn) that mimics the transmembrane cytoadhesion architecture. CoupOn simultaneously monitors mechanical strains with a gauge factor of ~34 and surface electromyogram with a signal-to-noise ratio of 32.2 dB. The resolved excitation-contraction signatures of forearm flexor muscles can recognize flexions of different fingers, hand grips of varying strength, and nervous and metabolic muscle fatigue. The orthogonal correlation of hand grip strength with speed is further exploited to manipulate robotic hands for recapitulating corresponding gesture dynamics. It can be envisioned that such locally coupled electromechanical interfaces would endow cyber-human interactions with unprecedented robustness and dexterity.

The Effectiveness of Electronic Health Interventions for Promoting HIV-Preventive Behaviors Among Men Who Have Sex With Men: Meta-Analysis Based on an Integrative Framework of Design and Implementation Features.

BACKGROUND: The disproportionately high prevalence of HIV among men who have sex with men (MSM) is a global concern. Despite the increasing utilization of electronic health (eHealth) technology in the delivery of HIV prevention interventions, few studies have systematically explored its effectiveness and association with various intervention characteristics. OBJECTIVE: This study aimed to conduct a meta-analysis of the effectiveness of eHealth technology-based interventions for promoting HIV-preventive behaviors among MSM and to determine effectiveness predictors within a framework integrating design and implementation features. METHODS: A systematic literature search using terms related to eHealth technology, HIV, the MSM population, and an experimental study design was performed using 5 databases (ie, MEDLINE, PsycINFO, EMBASE, Web of Science, and ProQuest Dissertations & Theses) and other sources (eg, bibliographies of relevant reviews and JMIR Publications). First, primary meta-analyses were conducted to estimate the effectiveness of eHealth interventions (d+) in changing 3 HIV-preventive behaviors among MSM: unprotected anal intercourse (UAI), HIV testing, and multiple sex partnership (MSP). Moderation analyses were then conducted to examine a priori effectiveness predictors including behavioral treatment components (eg, theory use, tailoring strategy use, navigation style, and treatment duration), eHealth technology components (eg, operation mode and modality type), and intervention adherence. RESULTS: A total of 46 studies were included. The overall effect sizes at end point were small but significant for all outcomes (UAI: d+=-.21, P<.001; HIV testing: d+=.38, P<.001; MSP: d+=-.26, P=.02). The intervention effects on UAI were significantly larger when compared with preintervention groups than with concurrent groups. Greater UAI reductions were associated with the increased use of tailoring strategies, provision of feedback, and tunneling navigation in interventions with a concurrent group, whereas reductions were associated with the use of self-paced navigation in interventions with a preintervention group. Greater uptake of HIV testing was associated with longer treatment duration; computer-mediated communication; and the use of messaging, social media, or a combined technology modality. Higher intervention adherence consistently predicted larger effects on UAI and HIV testing. CONCLUSIONS: This study provided empirical evidence for the effectiveness of eHealth interventions in promoting HIV-preventive behaviors among MSM. Features of treatment content and eHealth technology might best predict the intervention effects on UAI and HIV testing, respectively. Most importantly, intervention adherence tended to play an important role in achieving better effectiveness. The findings could help inform the development of efficacious interventions for HIV prevention in the future.

Morphing electronics enable neuromodulation in growing tissue.

Bioelectronics for modulating the nervous system have shown promise in treating neurological diseases1-3. However, their fixed dimensions cannot accommodate rapid tissue growth4,5 and may impair development6. For infants, children and adolescents, once implanted devices are outgrown, additional surgeries are often needed for device replacement, leading to repeated interventions and complications6-8. Here, we address this limitation with morphing electronics, which adapt to in vivo nerve tissue growth with minimal mechanical constraint. We design and fabricate multilayered morphing electronics, consisting of viscoplastic electrodes and a strain sensor that eliminate the stress at the interface between the electronics and growing tissue. The ability of morphing electronics to self-heal during implantation surgery allows a reconfigurable and seamless neural interface. During the fastest growth period in rats, morphing electronics caused minimal damage to the rat nerve, which grows 2.4-fold in diameter, and allowed chronic electrical stimulation and monitoring for 2 months without disruption of functional behavior. Morphing electronics offers a path toward growth-adaptive pediatric electronic medicine.

Recent developments on foaming mechanical and electronic techniques for the management of varicose veins.

Introduction: Varicose veins are a common disease, causing significant impairment of quality of life to afflicted individuals. Conventional surgery has represented the traditional treatment for years, with significant post-operative complications. By the end of the 20th century, novel approaches had been developed to induce biochemical sclerosis into the treated vein in order to exclude it from blood circulation.Areas covered: Foaming techniques for treatment of varicose veins, both clinically-approved methods and those under experimental studies. A brief description of cavitation, which is the basis of microbubbles formation, and an overview of foam properties have been also provided, including a discussion on clinical efficacy and safety profile.Expert commentary: Foam sclerotherapy has rapidly gained popularity since it represents the most minimally invasive and cost-effective procedure in the short term. Several different methods of foam preparation have been described in literature. In general, the foam generation method may affect characteristics such as stability and bubble size distribution, which in turn affect the therapeutic action of foam itself. Therefore, the selection of a suitable foaming technique is of importance for treatment success. Future developments on foaming techniques are expected to make sclerotherapy, already an effective treatment, even safer and more versatile therapeutic procedure.

Inkjet-printed stretchable and low voltage synaptic transistor array.

Wearable and skin electronics benefit from mechanically soft and stretchable materials to conform to curved and dynamic surfaces, thereby enabling seamless integration with the human body. However, such materials are challenging to process using traditional microelectronics techniques. Here, stretchable transistor arrays are patterned exclusively from solution by inkjet printing of polymers and carbon nanotubes. The additive, non-contact and maskless nature of inkjet printing provides a simple, inexpensive and scalable route for stacking and patterning these chemically-sensitive materials over large areas. The transistors, which are stable at ambient conditions, display mobilities as high as 30 cm2 V-1 s-1 and currents per channel width of 0.2 mA cm-1 at operation voltages as low as 1 V, owing to the ionic character of their printed gate dielectric. Furthermore, these transistors with double-layer capacitive dielectric can mimic the synaptic behavior of neurons, making them interesting for conformal brain-machine interfaces and other wearable bioelectronics.

Electronic Consultations in Allergy/Immunology.

BACKGROUND: Allergic condition management more often requires allergist guidance than allergy testing; necessary testing may be unavailable at initial drug allergy consultations. Electronic consultations (e-consults) provide expedited, problem-focused, potentially cost-saving care in other medical specialties, but have not yet been studied in Allergy/Immunology. OBJECTIVE: To describe e-consult use at an academic allergy/immunology practice. METHODS: E-consult data (August 10, 2016 through July 31, 2018) and in-person consult data (August 1, 2014 through July 31, 2018) were reviewed to determine consult volume, outcomes, indications, and timing. Referral reasons and wait times were compared with chi-square tests. RESULTS: E-consults grew from 1% to 10% of all new consults, with concurrent growth in in-person consults. Of 306 completed e-consults, 41 (13.4%) made diagnostic, therapeutic, or alternative referral recommendations, with 30 (73%) recommendations followed; 183 (59.8%) patients required an in-person Allergy/Immunology consult, and only 5 (<2%) patients saw an allergist without an e-consult recommendation to do so. E-consults were used more often than in-person consults for adverse drug reactions (66% vs 9%; P < .001), especially penicillin allergy (132, 61% of all e-consults) and immunodeficiency (15% vs 2%; P < .001). Allergists completed e-consults in a median of 11 minutes, with a median turnaround time of 22 hours. E-consult implementation was associated with a decreased median in-person consult wait time (1.5 fewer calendar days; P < .05). CONCLUSIONS: E-consults were increasingly used, particularly for historical adverse drug reactions and immunodeficiency. Implementation of an e-consult program resulted in decreased in-person wait times despite an increase in overall consult volume, supporting this model's ability to provide expedited, problem-focused care.

Effect of intermittent deployment of an electronic monitoring system on hand hygiene behaviors in healthcare workers.

BACKGROUND: Improving hand hygiene compliance among healthcare professionals is the most effective way to reduce healthcare-acquired infections. Electronic systems developed to increase hand hygiene performance show promise but might not maintain staff participation over time. In this study, we investigated an intermittent deployment strategy to overcome potentially declining participation levels. METHODS: An electronic monitoring system was deployed 3times at 6-month intervals on a musculoskeletal rehabilitation nursing unit in Toronto. Each deployment lasted 4 consecutive weeks. Each wall-mounted soap and hand rub dispenser was outfitted with an activation counter to assess the impact of system deployments on overall handwashing activity. RESULTS: System deployments took place in October 2016, April 2017, and October 2017. A total of 76,130 opportunities were recorded, with an aggregate hand hygiene performance of 67.43%. A total of 515,156 dispenser activations were recorded. There was a significant increase in aggregate dispenser use with every deployment and a decrease over several weeks following each withdrawal. Participation was high at the beginning of each deployment and declined during each deployment but was restored to a high level with the start of the next deployment. CONCLUSIONS: Intermittent deployment of an electronic monitoring intervention counteracts potential declines in participation rates sometimes seen with continuous system use. However, adoption of this strategy requires the acceptance of lower periods of performance between each deployment.

Effect of an Electronic Alert on Targeted HIV Testing Among High-Risk Populations.

CONTEXT: Screening for HIV infection in medical settings remains suboptimal. OBJECTIVE: To examine the real-world effectiveness of an electronic clinician alert on the same-day HIV testing rate and early diagnosis in high-risk populations. DESIGN: We identified Kaiser Permanente Southern California Health Plan members aged 14 years or older who received tests for sexually transmitted infections. MAIN OUTCOME MEASURES: Encounter-based same-day HIV testing rate, positive test result rate, and CD4+ cell count and HIV viral load at diagnosis. RESULTS: We identified 1,800,948 patients who made 2,326,701 health care encounters eligible for HIV testing before implementation (January 1, 2008 - June 30, 2012) and 1,362,479 eligible encounters after implementation (January 1, 2013 - June 30, 2015). The same-day HIV testing rate increased from 36.7% to 44.1% (standardized mean difference = 0.15, significant difference). The alert was associated with a moderate difference and statistically significant increase in the HIV testing rate (adjusted odds ratio = 1.17, 95% confidence interval = 1.16-1.18). The positive test result rate increased from 0.02% to 0.04% (p < 0.001). During the postimplementation period, fewer HIV-infected patients had a CD4+ cell count below 200 and/or an HIV viral load of 10,000 copies/mL or higher at diagnosis. CONCLUSION: Implementation of a targeted electronic alert embedded in the electronic medical record improved same-day HIV screening rate and positive test result rates among patients receiving tests for sexually transmitted infections in a large health organization. This intervention has potential for facilitating frequent screening and early identification of HIV infection in high-risk populations.

Adherencia al tratamiento con somatotropina administrada con dispositivo electrónico / Adherence to somatotropin treatment administered with an electronic device

Introducción: La adherencia al tratamiento con somatotropina se relaciona con el aumento de la velocidad de crecimiento y la mejora de la talla adulta. El objeto de este estudio es conocer la adherencia de pacientes en tratamiento con dispositivo electrónico y determinar la relación con diferentes variables (edad, sexo, duración del tratamiento, diagnóstico, talla y velocidad de crecimiento). Material y métodos: Estudio descriptivo, longitudinal y retrospectivo de menores de 14 años de la consulta de Endocrinología Pediátrica del Hospital General Universitario de Ciudad Real, en tratamiento con somatotropina administrada con el dispositivo electrónico Easypod(R). Se realiza seguimiento de la adherencia durante 12 meses. Se define adherencia según la fórmula: (días administrados a la dosis prescrita/días prescritos)×100. El análisis de los datos se realizó con el software SPSS. Resultados: Se recogió a 30 pacientes: predominio varones (57%), edad media 6,09 años, menores de 5 años el 51%. Las causas más frecuentes de tratamiento: pequeño para la edad gestacional (55%) y déficit de hormona de crecimiento (38%). Tiempo medio de tratamiento 4,3 años (3,6-5). Se evidenció una adherencia media del 92,3% (87,7-96,9), observándose una correlación significativa con la edad (R de Pearson = -0,384; p = 0,03) y la duración del tratamiento (R de Pearson = -0,537; p = 0,003). Conclusiones: La adherencia en nuestros pacientes con dispositivo electrónico es alta (92,3%), relacionándose inversamente con la edad y la duración del tratamiento. El uso de dispositivos electrónicos permite un seguimiento del cumplimiento terapéutico, lo que repercute en la optimización del tratamiento

Introduction: Adherence to somatotropin treatment is associated with increased growth velocity and improved adult height. The purpose of this study is to determine the adherence of patients undergoing treatment with an electronic device and its relationship with different variables (age, gender, duration of treatment, diagnosis, height, and growth rate). Material and methods: Descriptive, longitudinal and retrospective study of children less than 14 years of age undergoing treatment with somatotropin administered with the Easypod(R) electronic device in the Paediatric Endocrinology Outpatient Clinic of the General University Hospital of Ciudad Real, Spain. Adherence was monitored for 12 months and was defined according to the equation: (days administered at the prescribed dose / prescribed days)×100. The data analysis was performed using SPSS software. Results: Data were collected from 30 patients, with a predominance of males (57%), a mean age of 6.09 years, with 51% of children less than 5 years old. The most common reasons for the treatment were: small for gestational age (55%) and growth hormone deficiency (38%). The mean duration of treatment was 4.3 years (3.6-5). A mean adherence of 92.3% (87.7-96.9) was observed, and there was a significant correlation with age (Pearson R = -0.384, P=.03), and duration of treatment (Pearson R = -0.537; P=.003). Conclusions: The adherence in our patients with electronic device is high (92.3%), and is inversely associated with age and duration. The use of electronic devices allows monitoring of therapeutic compliance, which affects the optimisation of treatment

Flexible-Device Injector with a Microflap Array for Subcutaneously Implanting Flexible Medical Electronics.

Implantable electronics in soft and flexible forms can reduce undesired outcomes such as irritations and chronic damages to surrounding biological tissues due to the improved mechanical compatibility with soft tissues. However, the same mechanical flexibility also makes it difficult to insert such implants through the skin because of reduced stiffness. In this paper, a flexible-device injector that enables the subcutaneous implantation of flexible medical electronics is reported. The injector consists of a customized blade at the tip and a microflap array which holds the flexible implant while the injector penetrates through soft tissues. The microflap array eliminates the need of additional materials such as adhesives that require an extended period to release a flexible medical electronic implant from an injector inside the skin. The mechanical properties of the injection system during the insertion process are experimentally characterized, and the injection of a flexible optical pulse sensor and electrocardiogram sensor is successfully demonstrated in vivo in live pig animal models to establish the practical feasibility of the concept.

Molecular Approach to Conjugated Polymers with Biomimetic Properties.

The field of bioelectronics involves the fascinating interplay between biology and human-made electronics. Applications such as tissue engineering, biosensing, drug delivery, and wearable electronics require biomimetic materials that can translate the physiological and chemical processes of biological systems, such as organs, tissues. and cells, into electrical signals and vice versa. However, the difference in the physical nature of soft biological elements and rigid electronic materials calls for new conductive or electroactive materials with added biomimetic properties that can bridge the gap. Soft electronics that utilize organic materials, such as conjugated polymers, can bring many important features to bioelectronics. Among the many advantages of conjugated polymers, the ability to modulate the biocompatibility, solubility, functionality, and mechanical properties through side chain engineering can alleviate the issues of mechanical mismatch and provide better interface between the electronics and biological elements. Additionally, conjugated polymers, being both ionically and electrically conductive through reversible doping processes provide means for direct sensing and stimulation of biological processes in cells, tissues, and organs. In this Account, we focus on our recent progress in molecular engineering of conjugated polymers with tunable biomimetic properties, such as biocompatibility, responsiveness, stretchability, self-healing, and adhesion. Our approach is general and versatile, which is based on functionalization of conjugated polymers with long side chains, commonly polymeric or biomolecules. Applications for such materials are wide-ranging, where we have demonstrated conductive, stimuli-responsive antifouling, and cell adhesive biointerfaces that can respond to external stimuli such as temperature, salt concentration, and redox reactions, the processes that in turn modify and reversibly switch the surface properties. Furthermore, utilizing the advantageous chemical, physical, mechanical and functional properties of the grafts, we progressed into grafting of the long side chains onto conjugated polymers in solution, with the vision of synthesizing solution-processable conjugated graft copolymers with biomimetic functionalities. Examples of the developed materials to date include rubbery and adhesive photoluminescent plastics, biomolecule-functionalized electrospun biosensors, thermally and dually responsive photoluminescent conjugated polymers, and tunable self-healing, adhesive, and stretchable strain sensors, advanced functional biocidal polymers, and filtration membranes. As outlined in these examples, the applications of these biomimetic, conjugated polymers are still in the development stage toward truly printable, organic bioelectronic devices. However, in this Account, we advocate that molecular engineering of conjugated polymers is an attractive approach to a versatile class of organic electronics with both ionic and electrical conductivity as well as mechanical properties required for next-generation bioelectronics.

ASIC Implementation of a Nonlinear Dynamical Model for Hippocampal Prosthesis.

A hippocampal prosthesis is a very large scale integration (VLSI) biochip that needs to be implanted in the biological brain to solve a cognitive dysfunction. In this letter, we propose a novel low-complexity, small-area, and low-power programmable hippocampal neural network application-specific integrated circuit (ASIC) for a hippocampal prosthesis. It is based on the nonlinear dynamical model of the hippocampus: namely multi-input, multi-output (MIMO)-generalized Laguerre-Volterra model (GLVM). It can realize the real-time prediction of hippocampal neural activity. New hardware architecture, a storage space configuration scheme, low-power convolution, and gaussian random number generator modules are proposed. The ASIC is fabricated in 40 nm technology with a core area of 0.122 mm[Formula: see text] and test power of 84.4 [Formula: see text]W. Compared with the design based on the traditional architecture, experimental results show that the core area of the chip is reduced by 84.94% and the core power is reduced by 24.30%.

Optoelectronic system for brain neuronal network stimulation.

We propose an optoelectronic system for stimulation of living neurons. The system consists of an electronic circuit based on the FitzHugh-Nagumo model, an optical fiber, and a photoelectrical converter. We used this system for electrical stimulation of hippocampal living neurons in acute hippocampal brain slices (350-µm thick) obtained from a 20-28 days old C57BL/6 mouse or a Wistar rat. The main advantage of our system over other similar stimulators is that it contains an optical fiber for signal transmission instead of metallic wires. The fiber is placed between the electronic circuit and stimulated neurons and provides galvanic isolation from external electrical and magnetic fields. The use of the optical fiber allows avoiding electromagnetic noise and current flows which could affect metallic wires. Furthermore, it gives us the possibility to simulate "synaptic plasticity" by adaptive signal transfer through optical fiber. The proposed optoelectronic system (hybrid neural circuit) provides a very high efficiency in stimulating hippocampus neurons and can be used for restoring brain activity in particular regions or replacing brain parts (neuroprosthetics) damaged due to a trauma or neurodegenerative diseases.

Exploiting interfacial phenomena in organic bioelectronics: Conformable devices for bidirectional communication with living systems.

A novel fully organic bioelectronic device is presented and validated as electronic transducer and current stimulator for brain implants. The device integrates polymeric electrodes made of poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) on paper thin foils, resulting in a high surface-to-volume ratio architecture that exhibits high sensitivity to interfacial ionic transport phenomena. The prototyping technique herein presented yields devices for the bidirectional communication with biological systems whose dimensionality can be controlled according to the desired application. Transduction of ultra-low local-field potentials and delivery of voltage pulse-trains alike those used in deep-brain stimulation are herein assessed, paving the way towards novel theranostic strategies for the treatment of Parkinson's Disease and other severe neurodegenerative and/or traumatic pathologies of the central nervous system.

Implementation of an electronic routine outcome monitoring at an inpatient unit for psychosomatic medicine.

BACKGROUND: Patient-reported outcomes (PROs) can be part of an electronic routine outcome monitoring (eROM). eROM can improve patient involvement, treatment outcomes and simplify scientific data assessment. Available studies on eROM focus on its evaluation only and lack a detailed description of the prior implementation procedure. OBJECTIVE: The aim was to implement an eROM assessment at a division of Psychosomatic Medicine and provide a detailed description of the implementation procedure. METHODS: According to the Replicating Effective Program concept the project consisted of 4 phases: pre-condition (1), pre-implementation (2), implementation (3) and maintenance and evolution (4) mainly focusing the description of the implementation procedure and a short evaluation. RESULTS: We describe the actions taken during the implementation procedure and steps which were taken to overcome identified barriers. All decisions were carried out based on the Participatory Action Research process. A core set consisting of sociodemographic and clinical data and a comprehensive questionnaire battery covering symptoms, functioning parameters and psychological constructs was implemented. In total 164 patients, took part in the eROM assessment from June 2015 to December 2016. The evaluation showed that eROM was appreciated by health-care professionals (85.2%) and patients (70.2%) alike. The majority of patients (89.4%) and health-care professionals (85.7%) experienced no delays in daily clinical routine due to eROM. CONCLUSION: The detailed description of the implementation process can guide institutions planning to implement eROM into their daily clinical routine. Focusing scientific efforts on the implementation process is essential since this influences all further steps such as evaluation and acceptance.

Mesh Nanoelectronics: Seamless Integration of Electronics with Tissues.

Nanobioelectronics represents a rapidly developing field with broad-ranging opportunities in fundamental biological sciences, biotechnology, and medicine. Despite this potential, seamless integration of electronics has been difficult due to fundamental mismatches, including size and mechanical properties, between the elements of the electronic and living biological systems. In this Account, we discuss the concept, development, key demonstrations, and future opportunities of mesh nanoelectronics as a general paradigm for seamless integration of electronics within synthetic tissues and live animals. We first describe the design and realization of hybrid synthetic tissues that are innervated in three dimensions (3D) with mesh nanoelectronics where the mesh serves as both as a tissue scaffold and as a platform of addressable electronic devices for monitoring and manipulating tissue behavior. Specific examples of tissue/nanoelectronic mesh hybrids highlighted include 3D neural tissue, cardiac patches, and vascular constructs, where the nanoelectronic devices have been used to carry out real-time 3D recording of electrophysiological and chemical signals in the tissues. This novel platform was also exploited for time-dependent 3D spatiotemporal mapping of cardiac tissue action potentials during cell culture and tissue maturation as well as in response to injection of pharmacological agents. The extension to simultaneous real-time monitoring and active control of tissue behavior is further discussed for multifunctional mesh nanoelectronics incorporating both recording and stimulation devices, providing the unique capability of bidirectional interfaces to cardiac tissue. In the case of live animals, new challenges must be addressed, including minimally invasive implantation, absence of deleterious chronic tissue response, and long-term capability for monitoring and modulating tissue activity. We discuss each of these topics in the context of implantation of mesh nanoelectronics into rodent brains. First, we describe the design of ultraflexible mesh nanoelectronics with size features and mechanical properties similar to brain tissue and a novel syringe-injection methodology that allows the mesh nanoelectronics to be precisely delivered to targeted brain regions in a minimally invasive manner. Next, we discuss time-dependent histology studies showing seamless and stable integration of mesh nanoelectronics within brain tissue on at least one year scales without evidence of chronic immune response or glial scarring characteristic of conventional implants. Third, armed with facile input/output interfaces, we describe multiplexed single-unit recordings that demonstrate stable tracking of the same individual neurons and local neural circuits for at least 8 months, long-term monitoring and stimulation of the same groups of neurons, and following changes in individual neuron activity during brain aging. Moving forward, we foresee substantial opportunities for (1) continued development of mesh nanoelectronics through, for example, broadening nanodevice signal detection modalities and taking advantage of tissue-like properties for selective cell targeting and (2) exploiting the unique capabilities of mesh nanoelectronics for tackling critical scientific and medical challenges such as understanding and potentially ameliorating cell and circuit level changes associated with natural and pathological aging, as well as using mesh nanoelectronics as active tissue scaffolds for regenerative medicine and as neuroprosthetics for monitoring and treating neurological diseases.