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Introduction: Multi-channel electrophysiology systems for recording of neuronal activity face significant data throughput limitations, hampering real-time, data-informed experiments. These limitations impact both experimental neurobiology research and next-generation neuroprosthetics. Methods: We present a novel solution that leverages the high integration density of 22nm fully-depleted silicon-on-insulator technology to address these challenges. The proposed highly integrated programmable System-on-Chip (SoC) comprises 68-channel 0.41 μW/Ch recording frontends, spike detectors, 16-channel 0.87–4.39 μW/Ch action potentials and 8-channel 0.32 μW/Ch local field potential codecs, as well as a multiply-accumulate-assisted power-efficient processor operating at 25 MHz (5.19 μW/MHz). The system supports on-chip training processes for compression, training, and inference for neural spike sorting. The spike sorting achieves an average accuracy of 91.48 or 94.12% depending on the utilized features. The proposed programmable SoC is optimized for reduced area (9 mm2) and power. On-chip processing and compression capabilities free up the data bottlenecks in data transmission (up to 91% space saving ratio), and moreover enable a fully autonomous yet flexible processor-driven operation. Discussion: Combined, these design considerations overcome data-bottlenecks by allowing on-chip feature extraction and subsequent compression. [ABSTRACT FROM AUTHOR]

Implantable medical devices have revolutionized healthcare by providing continuous monitoring and therapeutic interventions within the human body. The overall performance of these devices is heavily dependent on the effectiveness and efficiency of integrated electronic components, such as transistors. This survey explores the growing utilization of Tunnel Field-Effect Transistors (TFETs) in implantable devices, shedding light on their advantages and challenges in this specific application domain. TFETs, characterized by their unique tunnelling mechanism, offer several advantages that make them well suited for implantable devices. Their low-power consumption, reduced leakage current, and improved subthreshold swing make them ideal for energy-efficient, long-lasting operation within the constrained power budgets of implantable devices. Furthermore, TFETs exhibit excellent performance at low supply voltages, ensuring minimal tissue damage and heat generation. This survey also addresses the challenges associated with TFETs in implantable devices, including fabrication complexities, variability, and compatibility with existing technologies. It highlights recent advancements in TFET technology that address these concerns, such as improved material choices and manufacturing techniques. As technology continues to advance, TFETs are poised to play a pivotal role in improving the overall efficiency and reliability of life-saving technologies and medical devices. Overall, this survey provides valuable insights into the current state and future prospects of TFETs in implantable devices, guiding researchers and engineers in harnessing their potential for the benefit of healthcare and patient well-being. [ABSTRACT FROM AUTHOR]

Bioelectronic implantable devices are adept at facilitating continuous monitoring of health and enabling the early detection of diseases, offering insights into the physiological conditions of various bodily organs. Furthermore, these advanced systems have therapeutic capabilities in neuromodulation, demonstrating their efficacy in addressing diverse medical conditions through the precise delivery of stimuli directly to specific targets. This comprehensive review explores developments and applications of bioelectronic devices within the biomedical field. Special emphasis is placed on the evolution of closed‐loop systems, which stand out for their dynamic treatment adjustments based on real‐time physiological feedback. The integration of Artificial Intelligence (AI) and edge computing technologies is discussed, which significantly bolster the diagnostic and therapeutic functions of these devices. By addressing elemental analyses, current challenges, and future directions in implantable devices, the review aims to guide the pathway for advances in bioelectronic devices. [ABSTRACT FROM AUTHOR]

Implantable cardiovascular devices have revolutionized the management of cardiovascular diseases, significantly enhancing patients' quality of life. With the increasing demand of cardiac implantable electronic devices, the imperative for novel device development is evident. This review article first elaborates the mechanisms underlying foreign body response and infection, elucidating the complex interplay between implanted constructs and host tissues. The discussion then focuses on current advancements in materials science and engineering aimed at mitigating these challenges. Material innovations, such as drug-eluting materials, surface modifications, and biomimetic materials, are explored as strategies to modulate these responses and to prevent fibrotic or thrombotic complications and infection. Finally, future directions in materials development for implantable cardiovascular devices are introduced. By addressing safety and patency concerns through innovative material strategies, this article aims to guide the research and development of advanced materials for both current and future cardiovascular implantable devices, ultimately improving patient outcomes and advancing cardiovascular disease treatment. [ABSTRACT FROM AUTHOR]

Long-term and high-precision intracranial biomarker monitoring is crucial for the diagnosis, prevention, and prognosis of various diseases. However, existing technologies are associated with several issues of poor measurement accuracy, inability to monitor long-term and inadequate biocompatibility. To address these, minimally invasive implantable ultrasound metagel sensors have been developed for monitoring intracranial pressure, temperature, pH, and blood flow velocity. The sensor can quickly respond to changes in ultrasound frequency for high-precision monitoring of key physiological signals compared to current clinical gold standards. Additionally, the hydrogel exhibits excellent biocompatibility and can degrade almost completely within 18 weeks, without causing hematological disorders or systemic inflammatory responses. Highlights: • Significance, challenge, and existing technologies of intracranial biomarker monitoring. • Design and characterization of ultrasound-sensitive metagel sensors for multimodal intracranial biomarker monitoring. • Conclusions and perspectives on the future development of intracranial biomarker monitoring. [ABSTRACT FROM AUTHOR]

Introduction. Modern clinical guidelines for heart failure consider a comprehensive approach to treatment using implantation of various devices (cardiac resynchronisation therapy CRT, implantation of cardioverter-defibrillator (ICD), installation of pacemakers (ECS) as well as correction of valve defects. For example, for treatment of severe mitral valve insufficiency the technique of clipping its flaps using MitraClip system is used. Objective. To evaluate the effect of mitral valve intervention with the help of MitraClip on the course of chronic heart failure (CHF) in patients with implanted devices. Materials and Methods. 73 patients with mitral regurgitation of 3-4 degree, heart failure of II-IV NYHA functional class who underwent implantation of MitraClip system on mitral valve flaps were included in the study. The dynamics of EchoCG parameters, exercise tolerance, diuretic therapy and brain natriuretic pro-peptide level was evaluated during six months. The comparison of the results of follow-up of the group of patients who had previously been fitted with ECS, ICD, CRT (group A) with the data of patients without implanted devices (group B) was carried out. Results. Clinical improvement of the course of CCN occurred after 6 months in both observation groups. The mean functional class (FC) of CHF decreased in group A from 2.67 ± 0.8 to 1.81 ± 0.7 (p

In vivo implantation of microelectrodes opens the door to studying neural circuits and restoring damaged neural pathways through direct electrical stimulation and recording. Although some neuroprostheses have achieved clinical success, electrode material properties, inflammatory response, and glial scar formation at the electrode-tissue interfaces affect performance and sustainability. Those challenges can be addressed by improving some of the materials' mechanical, physical, chemical, and electrical properties. This paper reviews materials and designs of current microelectrodes and discusses perspectives to advance neuroprosthetics performance.

Driven by the rapid advancement and practical implementation of biomaterials, fabrication technologies, and artificial intelligence, artificial neuron devices and systems have emerged as a promising technology for interpreting and transmitting neurological signals. These systems are equipped with multi-modal bio-integrable sensing capabilities, and can facilitate the benefits of neurological monitoring and modulation through accurate physiological recognition. In this article, we provide an overview of recent progress in artificial neuron technology, with a particular focus on the high-tech applications made possible by innovations in material engineering, new designs and technologies, and potential application areas. As a rapidly expanding field, these advancements have a promising potential to revolutionize personalized healthcare, human enhancement, and a wide range of other applications, making artificial neuron devices the future of brain-machine interfaces. [ABSTRACT FROM AUTHOR]

In epilepsy treatment, besides medication and surgery, devices that modulate abnormal brain activity are being developed. Intracranial devices like vagus nerve stimulation (VNS), deep brain stimulation (DBS), brain cooling, and drug delivery have seen significant advances in recent years. The process of developing these devices necessitates the use of animals, from the basic to applied research phases. Notably, research with large-sized animals is vital and provides insights that closely mirror human responses. Cats, dogs, and macaques are frequently used models in medicine, neuroscience, and biomedical engineering. However, ethical concerns, escalating costs, and other factors challenge the feasibility of their continued use. Nevertheless, the accumulated knowledge from research on these three species is indispensable for advancing epilepsy treatment techniques. Macaques have brain structures closely resembling humans, offering vital insights into human epilepsy. Meanwhile, cats and dogs present unique study cases. Dogs exhibit high spontaneous epilepsy rates, while established methods exist for inducing experimental convulsive seizures in cats. These devices are increasingly used as therapeutic options for treating domesticated cats and dogs. In this review, we explore research on therapeutic devices for epilepsy in cats, dogs, and macaques, underscoring the importance of these animal models and experimental methods. [ABSTRACT FROM AUTHOR]

Objectives: Implantable hypoglossal nerve stimulation (HNS) therapy is an evolving therapeutic alternative for patients with refractory obstructive sleep apnea (OSA). The muscular anatomy of this region has implications for surgical access through this zone as well as positioning and anchoring of hardware in this area. The purpose of this study was to radiologically describe the topography of the mylohyoid muscle and adjacent structures across a wide age spectrum. Methods: We retrospectively evaluated computed tomography scans of the neck in 102 patients who were imaged for reasons unrelated to the floor of mouth or submental space. Patients with prior surgery or pathology in the area of interest were excluded. Fourteen relevant muscle measurements were made on a midline sagittal image and a coronal image positioned at the midpoint between the hyoid bone and the mandible. Results: We included 49 men and 53 women with an average age of 44 years (range 19–70). The average mylohyoid length was 42 mm; the average distance between the anterior digastric bellies was 17 mm. The average angle of the central mylohyoid was 174° in the sagittal plane and 164° in the coronal plane. Several measurements were significantly correlated with patient age, including the angle measurements and the distance between the digastric muscles. Aberrant digastric anatomy was common. Conclusions: The mylohyoid muscle has multiple radiologically distinct segments with predictable curvatures. An understanding of submental muscular anatomy, along with its variability between patients, may be beneficial to the development of bilateral implantable neurostimulation technology for the treatment of refractory OSA. Level of Evidence: N/A Laryngoscope, 134:2970–2975, 2024 [ABSTRACT FROM AUTHOR]

Deep-brain stimulation (DBS) is a highly effective and safe medical treatment that improves the lives of patients with a wide range of neurological and psychiatric diseases. It has been established as a first-line tool in the treatment of these conditions for the past two decades. Closed-loop deep-brain stimulation (CLDBS) advances this tool further by automatically adjusting the stimulation parameters in real time based on the brain's response. In this context, this paper presents a low-noise amplifier (LNA) and a neurostimulator circuit fabricated using the low-power/low-voltage 65 nm CMOS process from TSMC. The circuits are specifically designed for implantable applications. To achieve the best tradeoff between input-referred noise and power consumption, metaheuristic algorithms were employed to determine and optimize the dimensions of the LNA devices during the design phase. Measurement results showed that the LNA had a gain of 41.2 dB; a 3 dB bandwidth spanning over three decades, from 1.5 Hz to 11.5 kHz; a power consumption of 5.9 µW; and an input-referred noise of 3.45 µVRMS, from 200 Hz to 11.5 kHz. The neurostimulator circuit is a programmable Howland current pump. Measurements have shown its capability to generate currents with arbitrary shapes and ranging from −325 µA to +318 µA. Simulations indicated a quiescent power consumption of 0.13 µW, with zero neurostimulation current. Both the LNA and the neurostimulator circuits are supplied with a 1.2 V voltage and occupy a microdevice area of 145 µm × 311 µm and 88 µm × 89 µm, respectively, making them suitable for implantation in applications involving closed-loop deep-brain stimulation. [ABSTRACT FROM AUTHOR]

Wearable devices, interactive human-machine interface equipment, wireless sensors, and small-scale cleaning devices play crucial roles in biomedical implantation, disease treatment, health monitoring, environmental purification, etc. These devices require a sustainable energy source to work effectively. With the consideration of the global energy crisis and environmental pollution, researchers are exploring new, stable, and environmentally friendly methods to power these low-powered devices. Mechanical energy is one of the most abundant natural energy sources. Converting mechanical energy from the ambient environment or host structures into electrical energy via the direct piezoelectric effect is an efficient energy harvesting technique. This paper reviews the application of advanced piezoelectric materials, and small-scale self-powered and self-sensing piezoelectric devices at the cubic centimeter scale in energy harvesting and health monitoring of human, animal, machinery, roads, bridges, as well as the pollutant degradation of the environment. Some of these devices have the capability to not only harvest mechanical energy but also enable real-time monitoring and analysis of the electrical signals generated by the direct piezoelectric effect, facilitating prompt decision-making and appropriate responses. In addition, potential challenges and future prospects of small-scale self-powered and self-sensing piezoelectric devices are discussed. [ABSTRACT FROM AUTHOR]

IntroductionMulti-channel electrophysiology systems for recording of neuronal activity face significant data throughput limitations, hampering real-time, data-informed experiments. These limitations impact both experimental neurobiology research and next-generation neuroprosthetics.MethodsWe present a novel solution that leverages the high integration density of 22nm fully-depleted silicon-on-insulator technology to address these challenges. The proposed highly integrated programmable System-on-Chip (SoC) comprises 68-channel 0.41 μW/Ch recording frontends, spike detectors, 16-channel 0.87–4.39 μW/Ch action potentials and 8-channel 0.32 μW/Ch local field potential codecs, as well as a multiply-accumulate-assisted power-efficient processor operating at 25 MHz (5.19 μW/MHz). The system supports on-chip training processes for compression, training, and inference for neural spike sorting. The spike sorting achieves an average accuracy of 91.48 or 94.12% depending on the utilized features. The proposed programmable SoC is optimized for reduced area (9 mm2) and power. On-chip processing and compression capabilities free up the data bottlenecks in data transmission (up to 91% space saving ratio), and moreover enable a fully autonomous yet flexible processor-driven operation.DiscussionCombined, these design considerations overcome data-bottlenecks by allowing on-chip feature extraction and subsequent compression.

The preparation of functional surfaces is one of the important methods to enhance the therapeutic performance and safety of medical devices. Currently, the fabrication of functional surface microstructures based on laser processing is widely used in the optimizing medical device surface properties. This paper reviews the current research status of functional microstructures for laser processing of medical implantable and surgical devices in terms of cell function regulation, antimicrobial properties, corrosion resistance, frictional properties, and anti-adhesion, etc. It analyzes the advantages and limitations of laser processing of functional surfaces for medical devices and outlines the development prospects of laser processing technology for functional surfaces for medical devices.

The genitourinary syndrome of menopause (GSM) is a widely occurring condition affecting millions of women worldwide. The current treatment of GSM involves the use of orally or vaginally administered estrogens, often with the risk of endometrial hyperplasia. The utilization of progestogens offers a means to counteract the effects of estrogen on the endometrial tissue, decreasing unwanted side effects and improving therapeutic outcomes. In this study, a norethindrone acetate (NETA)-loaded, hollow, cylindrical, and sustained release platform has been designed, fabricated, and optimized for implantation in the uterine cavity as a counter-estrogenic intervention in the treatment of GSM. The developed system, which comprises ethyl cellulose (EC) and polycaprolactone (PCL), has been statistically optimized using a two-factor, two-level factorial design, with the mechanical properties, degradation, swelling, and in vitro drug release of NETA from the device evaluated. The morphological characteristics of the platform were further investigated through scanning electron microscopy in addition to cytocompatibility studies using NIH/3T3 cells. Results from the statistical design highlighted the platform with the highest NETA load and the EC-to-PCL ratio that exhibited favorable release and weight loss profiles. The drug release data for the optimal formulation were best fitted with the Peppas–Sahlin model, implicating both diffusion and polymer relaxation in the release mechanism, with cell viability results noting that the prepared platform demonstrated favorable cytocompatibility. The significant findings of this study firmly establish the developed platform as a promising candidate for the sustained release of NETA within the uterine cavity. This functionality serves as a counter-estrogenic intervention in the treatment of GSM, with the platform holding potential for further advanced biomedical applications. [ABSTRACT FROM AUTHOR]

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Implantable neuromodulation devices have significantly advanced treatments for neurological disorders such as Parkinson's disease, epilepsy, and depression. Traditional open-loop devices like deep brain stimulation (DBS) and spinal cord stimulators (SCS) often lead to overstimulation and lack adaptive precision, raising safety and side-effect concerns. Next-generation closed-loop systems offer real-time monitoring and on-device diagnostics for responsive stimulation, presenting a significant advancement for treating a range of brain diseases. However, the high false alarm rates of current closed-loop technologies limit their efficacy and increase energy consumption due to unnecessary stimulations. In this study, we introduce an artificial intelligence-integrated circuit co-design that targets these issues and using an online demonstration system for closedloop seizure prediction to showcase its effectiveness. Firstly, two neural network models are obtained with neural-network search and quantization strategies. A binary neural network is optimized for minimal computation with high sensitivity and a convolutional neural network with a false alarm rate as low as 0.1/h for false alarm rejection. Then, a dedicated low-power processor is fabricated in 55 nm technology to implement the two models. With reconfigurable design and event-driven processing feature the resulting application-specific integrated circuit (ASIC) occupies only 5mm2 silicon area and the average power consumption is 142 µW. The proposed solution achieves a significant reduction in both false alarm rates and power consumption when benchmarked against state-of-the-art counterparts. [ABSTRACT FROM AUTHOR]

Online spike sorting provides on-the-fly single-neuron spiking activity that can be critical to real-time and implantable closed-loop neuromodulation devices, as well as advancing neuroscience. Neural recording electrodes can be manufactured with various configurations and sensing contact densities. Offline algorithms have improved rapidly by adapting to progressive electrode manufacturing technology. This paper proposes an unsupervised online spike-sorting algorithm that utilizes the tetrode’s 4-contact information for improved performance. This was achieved by incorporating the unique spatial signatures of the observed firing neurons extracted from the multi-contact electrode. The algorithm was evaluated on a realistic simulated neural spiking activity to assess the performance for varying numbers of ground-truth neurons and SNR values. For comparison, we extended Osort, the online sorting algorithm, to process tetrodes by concatenating the 4-contact waveforms. The results show improvements in accuracy and neuron yield, and a reduction in computational complexity, which is feasible for implantable devices. As expected, comparisons with offline methods show noticeable performance degradation; nevertheless, this work narrows the gap between online and offline tradeoffs, particularly for interactive neuroscience experiments.

Optogenetics is an advanced neural stimulation technique with high spatiotemporal precision. Various stimulation devices have been developed using microfabrication techniques to deliver light to specific population of neurons. However, traditional microfabrication techniques rely on clean room facilities, making the overall manufacturing process long and cumbersome. In this paper, we present an optical neural stimulator using an optical fiber coupled with a micro-sized light-emitting diode ( $\mu $ LED) for neuromodulation. The proposed system utilizes a 3D-printed mount to hold and couple the optical fiber with the $\mu $ LED which is also placed on a 3D-printed substrate with micrometer-sized conductive wires for electrical connection. As such, the proposed device fabrication and assembly steps are simple but efficient without using any semiconductor fabrication processes. In addition, the stimulation depth can be easily customized from the depth for the cortex to that of deep brain structures by simply cleaving the fiber with the desired length and integrating it with the mount. Electrical, optical, and thermal properties of the fabricated device are evaluated experimentally. The validation shows that the device can generate enough intensity light on the tip under a low-temperature change for the safety of the brain tissue. For validation of the device’s efficacy, the stimulator is implanted in the motor cortex of mice and is used to modulate the subject’s motor behaviors. The experiments show that there is an increase in the velocity of mice’s movement during the optical stimulation of the motor cortex. These results prove that the proposed device can successfully modulate the target neurons in the cortex.

Abstract Background There is a lack of evidence regarding contemporary implantable cardioverter-defibrillator (ICD) battery longevity. Our aim was to assess battery longevity in ICDs in a real-world setting. Methods Retrospective cross-sectional single center study of a prospectively collected database of consecutive patients who underwent ICD implantation from January 2010 to December 2015. Clinical data and battery longevity of all manufacturers were collected. Results A total of 351 patients (84.6% males, mean age of 61 ± 12 years) were included in the study (292 VVI; 6 VDD; 53 DDD). All manufacturers (Abbott, Biotronik, Boston, Medtronic and Microport) were equally represented in the study (p = 0.110). Median battery longevity was 10.8 years (11 years for VVI and 8.5 for DDD). After a follow-up time of 5 years, 98% of VVI and DDD were still in service (vs. industry-projected longevity of 98%). During this time, 89 patients (25.4%) underwent device replacement − 69 patients (77.5%) due to battery depletion, 6 patients due to infection, 3 patients due to dysfunction and 13 patients due to upgrade to CRT-D. Patients with Medtronic or Biotronik ICDs had a greater probability of being replaced earlier due to battery depletion (Biotronik HR 6.87, 95% CI 2.54–18.58, p

In recent years, portable and wearable personal electronic devices have rapidly developed with increasing mass production and rising energy consumption, creating an energy crisis. Using batteries and supercapacitors with limited lifespans and environmental hazards drives the need to find new, environmentally friendly, and renewable sources. One idea is to harness the energy of human motion and convert it into electrical energy using energy harvesting devices—piezoelectric nanogenerators (PENGs), triboelectric nanogenerators (TENGs) and hybrids. They are characterized by a wide variety of features, such as lightness, flexibility, low cost, richness of materials, and many more. These devices offer the opportunity to use new technologies such as IoT, AI or HMI and create smart self-powered sensors, actuators, and self-powered implantable/wearable devices. This review focuses on recent examples of PENGs, TENGs and hybrid devices for wearable and implantable self-powered systems. The basic mechanisms of operation, micro/nano-scale material selection and manufacturing processes of selected examples are discussed. Current challenges and the outlook for the future of the nanogenerators are also discussed. [ABSTRACT FROM AUTHOR]

Treatment nonadherence is a pressing issue in people living with HIV (PLWH), as they require lifelong therapy to maintain viral suppression. Poor adherence leads to antiretroviral (ARV) resistance, transmission to others, AIDS progression, and increased morbidity and mortality. Long-acting (LA) ARV therapy is a promising strategy to combat the clinical drawback of user-dependent dosing. Islatravir (ISL) is a promising candidate for HIV treatment given its long half-life and high potency. Here we show constant ISL release from a subdermal LA nanofluidic implant achieves viral load reduction in SHIV-infected macaques. Specifically, a mean delivery dosage of 0.21 ± 0.07 mg/kg/day yielded a mean viral load reduction of −2.30 ± 0.53 log 10 copies/mL at week 2, compared to baseline. The antiviral potency of the ISL delivered from the nanofluidic implant was higher than oral ISL dosed either daily or weekly. At week 3, viral resistance to ISL emerged in 2 out of 8 macaques, attributable to M184V mutation, supporting the need of combining ISL with other ARV for HIV treatment. The ISL implant produced moderate reactivity in the surrounding tissue, indicating tolerability. Overall, we present the ISL subdermal implant as a promising approach for LA ARV treatment in PLWH. [Display omitted] • Sustained subQ delivery of islatravir shows significant viral load reduction in NHP. • SubQ delivery of islatravir shows higher potency than daily or weekly oral dosing. • 25% of NHP showed emergence of M184V mutation with islatravir monotherapy. • SubQ delivery of islatravir was well tolerated in SHIV-infected NHPs. [ABSTRACT FROM AUTHOR]

Background and Aims The European Union Medical Device Regulation 2017/745 challenges key stakeholders to follow transparent and rigorous approaches to the clinical evaluation of medical devices. The purpose of this study is a systematic evaluation of published clinical evidence underlying selected high-risk cardiovascular medical devices before and after market access in the European Union (CE-marking) between 2000 and 2021. Methods Pre-specified strategies were applied to identify published studies of prospective design evaluating 71 high-risk cardiovascular devices in seven different classes (bioresorbable coronary scaffolds, left atrial appendage occlusion devices, transcatheter aortic valve implantation systems, transcatheter mitral valve repair/replacement systems, surgical aortic and mitral heart valves, leadless pacemakers, subcutaneous implantable cardioverter-defibrillator). The search time span covered 20 years (2000–21). Details of study design, patient population, intervention(s), and primary outcome(s) were summarized and assessed with respect to timing of the corresponding CE-mark approval. Results At least one prospective clinical trial was identified for 70% (50/71) of the pre-specified devices. Overall, 473 reports of 308 prospectively designed studies (enrolling 97 886 individuals) were deemed eligible, including 81% (251/308) prospective non-randomized clinical trials (66 186 individuals) and 19% (57/308) randomized clinical trials (31 700 individuals). Pre-registration of the study protocol was available in 49% (150/308) studies, and 16% (48/308) had a peer-reviewed publicly available protocol. Device-related adverse events were evaluated in 82% (253/308) of studies. An outcome adjudication process was reported in 39% (120/308) of the studies. Sample size was larger for randomized in comparison to non-randomized trials (median of 304 vs. 100 individuals, P <.001). No randomized clinical trial published before CE-mark approval for any of the devices was identified. Non-randomized clinical trials were predominantly published after the corresponding CE-mark approval of the device under evaluation (89%, 224/251). Sample sizes were smaller for studies published before (median of 31 individuals) than after (median of 135 individuals) CE-mark approval (P <.001). Clinical trials with larger sample sizes (>50 individuals) and those with longer recruitment periods were more likely to be published after CE-mark approval, and were more frequent during the period 2016–21. Conclusions The quantity and quality of publicly available data from prospective clinical investigations across selected categories of cardiovascular devices, before and after CE approval during the period 2000–21, were deemed insufficient. The majority of studies was non-randomized, with increased risk of bias, and performed in small populations without provision of power calculations, and none of the reviewed devices had randomized trial results published prior to CE-mark certification. [ABSTRACT FROM AUTHOR]

The last decade has witnessed remarkable advancements in bioelectronics, ushering in a new era of wearable and implantable devices for drug delivery. By utilizing miniaturized system design and/or flexible materials, bioelectronics illustrates ideal integration with target organs and tissues, making them ideal platforms for localized drug delivery. Furthermore, the development of electrically assisted drug delivery systems has enhanced the efficiency and safety of therapeutic administration, particularly for the macromolecules that encounter additional challenges in penetrating biological barriers. In this review, a concise overview of recent progress in bioelectronic devices for in vivo localized drug delivery, with highlights on the latest trends in device design, working principles, and their corresponding functionalities, is provided. The reported systems based on their targeted delivery locations as wearable systems, ingestible systems, and implantable systems are categorized. Each category is introduced in detail by highlighting the special requirements for devices and the corresponding solutions. The remaining challenges in this field and future directions are also discussed. [ABSTRACT FROM AUTHOR]

Background: There is a lack of evidence regarding contemporary implantable cardioverter-defibrillator (ICD) battery longevity. Our aim was to assess battery longevity in ICDs in a real-world setting. Methods: Retrospective cross-sectional single center study of a prospectively collected database of consecutive patients who underwent ICD implantation from January 2010 to December 2015. Clinical data and battery longevity of all manufacturers were collected. Results: A total of 351 patients (84.6% males, mean age of 61 ± 12 years) were included in the study (292 VVI; 6 VDD; 53 DDD). All manufacturers (Abbott, Biotronik, Boston, Medtronic and Microport) were equally represented in the study (p = 0.110). Median battery longevity was 10.8 years (11 years for VVI and 8.5 for DDD). After a follow-up time of 5 years, 98% of VVI and DDD were still in service (vs. industry-projected longevity of 98%). During this time, 89 patients (25.4%) underwent device replacement − 69 patients (77.5%) due to battery depletion, 6 patients due to infection, 3 patients due to dysfunction and 13 patients due to upgrade to CRT-D. Patients with Medtronic or Biotronik ICDs had a greater probability of being replaced earlier due to battery depletion (Biotronik HR 6.87, 95% CI 2.54–18.58, p < 0.001; Medtronic HR 6.08, 95% CI 2.45–15.06 p < 0.001). Conclusions: VVI and DDD ICD battery longevity matched industry-projected longevity after 5 years of follow-up. Medtronic and Biotronik ICDs appeared to have an earlier battery depletion. Further randomized studies are required to ensure optimal care. [ABSTRACT FROM AUTHOR]

Background: Brady- and tachyarrhythmias commonly complicate adult congenital heart disease (ACHD). Permanent pacemakers (PPMs) or implantable cardioverter–defibrillators (ICDs) are often utilised to prevent morbidity or mortality related to arrhythmia, but can also be associated with significant morbidity themselves. Methods: We analysed outcomes from patients in our comprehensive ACHD database who were seen at least twice since 2000 and once since 2018. Of 1953 ACHD patients, 134 had a PPM and 78 had an ICD (47 for primary and 31 for secondary prevention). Results: For PPM patients, 41% had a pacing percentage below 33%, 13% had 33–66%, and 46% had above 66%. One fifth required PPM upgrade, most to cardiac resynchronisation therapy, the rest to ICD. There were 33 appropriate ICD shocks in 15 patients (19%) and 34 inappropriate shocks in 13 patients (17%) over a median follow up of 4.6 years (IQR 0.9–8.3 years). Anti-tachycardia pacing was delivered appropriately for 28% of patients and inappropriately for 9%.Apart from inappropriate therapy, one third of PPM and ICD patients had other device-related complications. Acute PPM complications included lead dysfunction requiring revision (2%), pneumothorax (2%), pleural effusion (2%) and pocket infection (2%). ICDs were also acutely complicated by lead dysfunction (4%) as well as pocket hematoma (3%). The most common long-term complication overall was lead dysfunction, affecting one sixth of both PPM and ICD patients. Finally, the rate of device insertion increased significantly with disease severity. Conclusions: Anti-arrhythmic devices can be lifesaving in ACHD patients, but inappropriate therapy and device-related complications are very common.

The emerging desire for implantable devices assisting individuals’ medical treatments requires their connection to systems placed outside and inside the human body. Their exchange of crucial information on health parameters at different locations may allow them to optimize the patient’s therapy by evaluating the received and transmitted data. Electromagnetic communication methods are the current implementation of choice for such applications. Yet, this kind of communication is often limited to shorter distances due to their restrictions on safe electromagnetic levels, causing no damaging heat dissipation in human tissue. In contrast, employing ultrasound as an alternative method will allow for long-distance communication in the same medium by simultaneously guaranteeing safety requirements for the patient. In this contribution, we will demonstrate a proof-of-concept for which we modulate ultrasonic carrier signals with the help of a low-power consumption microcontroller TI-MSP430. For this, two identical non-focused ultrasonic transducers will be used to receive and send messages through a tissue-mimicking phantom placed in a water tank, indicating the potential of ultrasonic signals as the carrier of information.

Driven by the rapid advancement and practical implementation of biomaterials, fabrication technologies, and artificial intelligence, artificial neuron devices and systems have emerged as a promising technology for interpreting and transmitting neurological signals. These systems are equipped with multi-modal bio-integrable sensing capabilities, and can facilitate the benefits of neurological monitoring and modulation through accurate physiological recognition. In this article, we provide an overview of recent progress in artificial neuron technology, with a particular focus on the high-tech applications made possible by innovations in material engineering, new designs and technologies, and potential application areas. As a rapidly expanding field, these advancements have a promising potential to revolutionize personalized healthcare, human enhancement, and a wide range of other applications, making artificial neuron devices the future of brain-machine interfaces.

Abstract Background Tissue-integrated micro-electronic devices for neural stimulation hold great potential in restoring the functionality of degenerated organs, specifically, retinal prostheses, which are aimed at vision restoration. The fabrication process of 3D polymer-metal devices with high resolution and a high aspect-ratio (AR) is very complex and faces many challenges that impair its functionality. Approach Here we describe the optimization of the fabrication process of a bio-functionalized 3D high-resolution 1mm circular subretinal implant composed of SU-8 polymer integrated with dense gold microelectrodes (23μm pitch) passivated with 3D micro-well-like structures (20μm diameter, 3μm resolution). The main challenges were overcome by step-by-step planning and optimization while utilizing a two-step bi-layer lift-off process; bio-functionalization was carried out by N2 plasma treatment and the addition of a bio-adhesion molecule. Main results In-vitro and in-vivo investigations, including SEM and FIB cross section examinations, revealed a good structural design, as well as a good long-term integration of the device in the rat sub-retinal space and cell migration into the wells. Moreover, the feasibility of subretinal neural stimulation using the fabricated device was demonstrated in-vitro by electrical activation of rat’s retina. Conclusions The reported process and optimization steps described here in detail can aid in designing and fabricating retinal prosthetic devices or similar neural implants.

Jennifer Llewellyn,1 Erin Barker,2 Catherine Bowe,2 Natalie Hallas,3,&ast; Ralphael Oghagbon,3,&ast; Archana Rao1 1Liverpool Heart and Chest Hospital, Liverpool, UK; 2York Health Economics Consortium, University of York, Heslington, York, UK; 3Medtronic, Watford, Herts, UK&ast;These authors contributed equally to this workCorrespondence: Jennifer Llewellyn, Liverpool Heart and Chest Hospital, Thomas Drive, Liverpool, L14 3PE, UK, Tel +44 0151 600 1616, Fax +44 0151 600 1862, Email jennifer.llewellyn@lhch.nhs.ukObjective: High voltage devices (implantable cardiac defibrillators (ICDs) and cardiac resynchronization therapy defibrillators referred to jointly as ICDs) reduce rates of sudden cardiac death in patients with cardiovascular disease. However, shocks from ICDs may be associated with healthcare resource use (HCRU) and costs. The aim of this study was to estimate the costs associated with both appropriate and inappropriate shocks from ICDs.Methods: Patients with appropriate and inappropriate shocks from ICDs were identified via CareLink data from Liverpool Heart and Chest Hospital between March 2017 and March 2019. The devices were SmartShock activated, with anti-tachycardia pacing. Costs were estimated according to the dominant episode of healthcare, from an NHS payer perspective.Results: There were 2445 patients on the CareLink system with ICDs. Over the two-year period, HCRU data from 143 shock episodes among 112 patients were reported. The total cost for all shocks was £ 252,552 with mean costs of £ 1608 and £ 2795 for appropriate and inappropriate shocks respectively. There was substantial variation in HCRU between shock episodes.Conclusion: While there was a low rate of inappropriate shocks from ICDs, there were still substantial HCRU and costs incurred. In this study, the specific HCRU was not costed independently, meaning the costs reported are likely to be a conservative estimate. Whilst every attempt to reduce shocks should be made, appropriate shocks cannot be avoided. Strategies to reduce the incidence of inappropriate and unnecessary shocks should be implemented to reduce overall health care costs associated with ICDs.Keywords: cardiology, implantable devices, hospital costs

Superior vena cava syndrome (SVCS) is due to impaired venous outflow from the head, neck, limbs and upper half of the body into the right atrium due to stenosis or complete obstruction of the superior vena cava (SVC). Increased venous pressure in the SVC and lack of timely treatment leads not only to serious complications, but also to death. In recent years, the etiology of SVCS has changed dramatically, mainly due to an increase in the number of implanted intravascular devices (central venous catheters, pacemakers, defibrillators, and other devices). Endovascular methods have become widely used in the treatment of patients with SVCS. This was primarily due to the minimally invasive nature of the intervention, the high technical success of the operation and the rapid onset of clinical improvement. Patients who develop SVCS after device implantation are predominantly younger and have a longer life expectancy. When choosing a treatment method, it is extremely important to take these factors into account and give preference to methods providing a long-term effect with the fewest possible complications. The article presents a case of endovascular treatment of a patient with SVCS occlusion, which developed 9 years after pacemaker implantation, using intravascular imaging methods.

This paper presents a 9-bit differential, minimum-powered, successive approximation register (SAR) ADC intended for implantable devices or sensors. Such applications demand nanowatt-range power consumption, which is achieved by designing the SAR ADC with a proposed bootstrap switch, bespoke split-capacitive DAC, customized comparator and a modified dynamic bit-slice unit for SAR logic. The linearity of the ADC is improved by introducing a bootstrap switch with a low clock feedthrough and threshold voltage variations along with the disseminated attenuation capacitor in the split-capacitive DAC. The dynamic comparator is customized to be simple in terms of the number of transistors to gain the advantage of low power and is also designed to have a low dynamic offset voltage. The stacking concept is embedded in the bit-slice unit of SAR logic to achieve reduced leakage power. This paper is concerned with how to contribute to low power consumption in all the aspects possible related to the implementation of the SAR ADC. With a 0.4 V supply and at 2 kS/s, the proposed ADC achieves an SNDR of 52.52 dB and a power consumption of 5.29 nW, resulting in a figure of merit (FOM) of 7.66 fJ/conversion-step. [ABSTRACT FROM AUTHOR]

Peripheral nerve stimulation has been demonstrated as a viable alternative to sacral nerve stimulation in managing refractory overactive bladder (OAB). New technologies allow the internalization of tibial nerve stimulators through various apparatuses. One such device, the eCoin, is a small, coin-shaped device that can be implanted adjacent to the tibial nerve that provides pre-programmed stimulation. We will review the literature on eCoin implantation, from proof of concept to mid-term data, with the longest period of follow-up being 12 months. All studies on this technology will be reviewed, along with an analysis of the current state of play in implantable neuromodulators for overactive bladder. Efficacy, durability, adverse events, and viability of eCoin as a long-term management option will be considered. The eCoin device demonstrates promising early data for efficacy in managing overactive bladder symptoms. Complication rates remain low and are mostly related to wound healing following the initial placement of the device. Research into the continued improvement and modification of the device appears optimistic, but longer-term data still need to be obtained. Indeed, implantable PTNS have a role in the future management of overactive bladder, and devices such as eCoin will still need to prove a long-term benefit to be a mainstay of management. [ABSTRACT FROM AUTHOR]

It may soon become possible not just to replace, but to re-grow healthy tissues after injury or disease, because of innovations in the field of Regenerative Medicine. One particularly promising innovation is a regenerative valve implant to treat people with heart valve disease. These implants are fabricated from so-called ‘smart’, ‘lifelike’ materials. Implanted inside a heart, these implants stimulate re-growth of a healthy, living heart valve. While the technological development advances, the ethical implications of this new technology are still unclear and a clear conceptual understanding of the notions ‘smart' and ‘lifelike' is currently lacking. In this paper, we explore the conceptual and ethical implications of the development of smart lifelike materials for the design of regenerative implants, by analysing heart valve implants as a showcase. In our conceptual analysis, we show that the materials are considered ‘smart’ because they can communicate with human tissues, and ‘lifelike’ because they are structurally similar to these tissues. This shows that regenerative valve implants become intimately integrated in the living tissues of the human body. As such, they manifest the ontological entanglement of body and technology. In our ethical analysis, we argue this is ethically significant in at least two ways: It exacerbates the irreversibility of the implantation procedure, and it might affect the embodied experience of the implant recipient. With our conceptual and ethical analysis, we aim to contribute to responsible development of smart lifelike materials and regenerative implants. [ABSTRACT FROM AUTHOR]

Despite advances in a wide range of device applications of hydrogels, including implantable ones, a method for deploying patterned hydrogel devices into the body in a minimally‐invasive manner is not available yet. However, in situ patterning of the hydrogel in vivo has an obvious advantage, by which incision surgery for implantation of the hydrogel device can be avoided. Here, a minimally‐invasive and in vivo hydrogel patterning method for in situ fabrication of implantable hydrogel devices is presented. The sequential application of injectable hydrogels and enzymes, with assistance of minimally‐invasive surgical instruments, enables the in vivo and in situ hydrogel patterning. This patterning method can be achieved by adopting an appropriate combination of the sacrificial mold hydrogel and the frame hydrogel, in consideration of unique material properties of the hydrogels such as high softness, facile mass transfer, biocompatibility, and diverse crosslinking mechanisms. In vivo and in situ patterning of the hydrogels functionalized with nanomaterials is also demonstrated to fabricate the wireless heater and tissue scaffold, showcasing broad applicability of the patterning method. [ABSTRACT FROM AUTHOR]

Malignant tumors have the capability to metastasize and colonize, meaning that they can spread to other organs and tissues, distributing metastatic focus and are hard to target. Although significant advances have been made in cancer treatment, it remains one of the leading causes of death around the globe. In recent years, new-emerging implantable systems and devices have been developed to tackle the challenge of metastatic tumors. In this review, implantable systems for suppressing tumors and preventing tumor recurrence are reported. In particular, we emphasize the responsive drug delivery systems and the external field assisted catalytic therapy for tumor treatment, as well as implantable biosensors for tumor microenvironment monitoring. We also conclude the open challenges and future perspectives of implantable systems and devices for cancer therapy and sensing. [ABSTRACT FROM AUTHOR]

Deep-brain stimulation (DBS) is a highly effective and safe medical treatment that improves the lives of patients with a wide range of neurological and psychiatric diseases. It has been established as a first-line tool in the treatment of these conditions for the past two decades. Closed-loop deep-brain stimulation (CLDBS) advances this tool further by automatically adjusting the stimulation parameters in real time based on the brain’s response. In this context, this paper presents a low-noise amplifier (LNA) and a neurostimulator circuit fabricated using the low-power/low-voltage 65 nm CMOS process from TSMC. The circuits are specifically designed for implantable applications. To achieve the best tradeoff between input-referred noise and power consumption, metaheuristic algorithms were employed to determine and optimize the dimensions of the LNA devices during the design phase. Measurement results showed that the LNA had a gain of 41.2 dB; a 3 dB bandwidth spanning over three decades, from 1.5 Hz to 11.5 kHz; a power consumption of 5.9 µW; and an input-referred noise of 3.45 µVRMS, from 200 Hz to 11.5 kHz. The neurostimulator circuit is a programmable Howland current pump. Measurements have shown its capability to generate currents with arbitrary shapes and ranging from −325 µA to +318 µA. Simulations indicated a quiescent power consumption of 0.13 µW, with zero neurostimulation current. Both the LNA and the neurostimulator circuits are supplied with a 1.2 V voltage and occupy a microdevice area of 145 µm × 311 µm and 88 µm × 89 µm, respectively, making them suitable for implantation in applications involving closed-loop deep-brain stimulation.

The genitourinary syndrome of menopause (GSM) is a widely occurring condition affecting millions of women worldwide. The current treatment of GSM involves the use of orally or vaginally administered estrogens, often with the risk of endometrial hyperplasia. The utilization of progestogens offers a means to counteract the effects of estrogen on the endometrial tissue, decreasing unwanted side effects and improving therapeutic outcomes. In this study, a norethindrone acetate (NETA)-loaded, hollow, cylindrical, and sustained release platform has been designed, fabricated, and optimized for implantation in the uterine cavity as a counter-estrogenic intervention in the treatment of GSM. The developed system, which comprises ethyl cellulose (EC) and polycaprolactone (PCL), has been statistically optimized using a two-factor, two-level factorial design, with the mechanical properties, degradation, swelling, and in vitro drug release of NETA from the device evaluated. The morphological characteristics of the platform were further investigated through scanning electron microscopy in addition to cytocompatibility studies using NIH/3T3 cells. Results from the statistical design highlighted the platform with the highest NETA load and the EC-to-PCL ratio that exhibited favorable release and weight loss profiles. The drug release data for the optimal formulation were best fitted with the Peppas–Sahlin model, implicating both diffusion and polymer relaxation in the release mechanism, with cell viability results noting that the prepared platform demonstrated favorable cytocompatibility. The significant findings of this study firmly establish the developed platform as a promising candidate for the sustained release of NETA within the uterine cavity. This functionality serves as a counter-estrogenic intervention in the treatment of GSM, with the platform holding potential for further advanced biomedical applications.

Background: Tissue-integrated micro-electronic devices for neural stimulation hold great potential in restoring the functionality of degenerated organs, specifically, retinal prostheses, which are aimed at vision restoration. The fabrication process of 3D polymer-metal devices with high resolution and a high aspect-ratio (AR) is very complex and faces many challenges that impair its functionality. Approach: Here we describe the optimization of the fabrication process of a bio-functionalized 3D high-resolution 1mm circular subretinal implant composed of SU-8 polymer integrated with dense gold microelectrodes (23μm pitch) passivated with 3D micro-well-like structures (20μm diameter, 3μm resolution). The main challenges were overcome by step-by-step planning and optimization while utilizing a two-step bi-layer lift-off process; bio-functionalization was carried out by N2 plasma treatment and the addition of a bio-adhesion molecule. Main results: In-vitro and in-vivo investigations, including SEM and FIB cross section examinations, revealed a good structural design, as well as a good long-term integration of the device in the rat sub-retinal space and cell migration into the wells. Moreover, the feasibility of subretinal neural stimulation using the fabricated device was demonstrated in-vitro by electrical activation of rat's retina. Conclusions: The reported process and optimization steps described here in detail can aid in designing and fabricating retinal prosthetic devices or similar neural implants. [ABSTRACT FROM AUTHOR]