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Wearable and implantable devices play a crucial role in clinical diagnosis, disease treatment, and fundamental research on the body's electrophysiology and biochemical processes. Conducting polymers are emerging as promising solutions to surpass the limitations of traditional metal‐based electrodes, offering enhanced conformability, and stretchability. However, current microfabrication techniques of CP electrodes have a number of limitations. In this study, a novel wet‐printing technique is developed for the fabrication of highly stretchable poly(3,4‐ethylenedioxythiophene): polystyrene sulfonate (PEDOT:PSS) microelectrodes. The wet‐printing, conducted in a liquid coagulation bath, has the advantages of being non‐contact, easy and fast to perform, and capable of printing low‐viscosity inks. Wet‐printing of PEDOT:PSS lines with a width of ≈20 µm is demonstrated. By adding D‐sorbitol as a plasticizer, an ultra‐high stretchability of PEDOT:PSS electrodes, of more than 720% is achieved while the electrodes remained conductive and strain‐insensitive up to high strains. The use of PEDOT:PSS wet‐printed electrode arrays for the electrophysiological recording from the stomach is demonstrated. The stretchable electrodes conformed swell to the tissue and recorded comparable electrophysiological signals to Au‐plated electrodes in porcine and rodent animal models. The wet‐printing approach to fabricating flexible and stretchable electrode arrays using low‐viscosity, conducting inks holds promise for applications in conformable electronics. [ABSTRACT FROM AUTHOR]

Automated drug delivery systems (ADDS) improve chronic disease management by enhancing adherence and reducing patient burden, particularly in conditions like type 1 diabetes, through intraperitoneal insulin delivery. However, periodic invasive refilling of the reservoir is needed in such a class of implantable devices. In previous work, an implantable ADDS with a capsule docking system is introduced for non‐invasive reservoir refilling. Yet, it encounters reliability issues in manufacturing, sealing, and docking design and lacks evidence on intestinal tissue compression effects and chronic in vivo data. This work proposes an optimization of the different components featuring this ADDS. The ingestible capsule is designed, developed, and tested following ISO 13485, exhibiting high insulin stability and optimal sealing for six days in harsh gastrointestinal‐like conditions. A magnetic docking system is optimized, ensuring reliable and stable capsule docking at a clinically relevant distance of 5.92 mm. Histological tests on human intestinal tissues confirm safe capsule compression during docking. Bench tests demonstrate that the integrated mechatronic system effectively docks capsules at various peristalsis‐mimicking velocities. A six‐week in vivo test on porcine models demonstrates chronic safety and provides hints on fibrotic reactions. These results pave the way for the further evolution of implantable ADDS. [ABSTRACT FROM AUTHOR]

The treatment for Glioblastoma is limited due to the presence of the blood brain barrier, which restricts the entry of chemotherapeutic drugs into the brain. Local delivery into the tumor resection margin has the potential to improve efficacy of chemotherapy. We developed a safe and clinically translatable irinotecan implant for local delivery to increase its efficacy while minimizing systemic side effects. Irinotecan-loaded implants were manufactured using hot melt extrusion, gamma sterilized at 25 kGy, and characterized for their irinotecan content, release, and drug diffusion. Their therapeutic efficacy was evaluated in a patient-derived xenograft mouse resection model of glioblastoma. Their safety and translatability were evaluated using histological analysis of brain tissue and serum chemistry analysis. Implants containing 30% and 40% w/w irinotecan were manufactured without plasticizer. The 30% and 40% implants showed moderate local toxicity up to 2- and 6-day post-implantation. Histopathology of the implantation site showed signs of necrosis at days 45 and 14 for the 30% and 40% implants. Hematological analysis and clinical chemistry showed no signs of serious systemic toxicity for either implant. The 30% implants had an 80% survival at day 148, with no sign of tumor recurrence. Gamma sterilization and 12-month storage had no impact on the integrity of the 30% implants. This study demonstrates that the 30% implants are a promising novel treatment for glioblastoma that could be quickly translated into the clinic. [ABSTRACT FROM AUTHOR]

Achieving negative surgical margins, defined as no tumor found on the edges of the resected tissue, during lumpectomy for breast cancer is critical for mitigating the risk of local recurrence. To identify nonpalpable tumors that cannot be felt, pre-operative placements of wire and wire-free localization devices are typically employed. Wire-free localization approaches have significant practical advantages over wired techniques. In this study, we introduce an innovative localization system comprising a light-emitting diode (LED)-based implantable device and handheld system. The device, which is needle injectable and wire free, utilizes multiple wirelessly powered LEDs to provide direct visual guidance for lumpectomy. Two distinct colors, red and blue, provide a clear indication of tissue depth: blue light is absorbed strongly in tissue, visible within a close range of <1 cm, while red light remains visible through several centimeters of tissue. The LEDs, integrated with an impedance-matching circuit and receiver coil, are encapsulated in biocompatible epoxy for injection with a 12 G needle. Our findings demonstrate that the implant exhibits clearly perceivable depth-dependent color changes and remains visible through >2 cm of ex vivo chicken breast and bovine muscle tissue using less than 4 W of transmitted power from a handheld antenna. These miniaturized needle-injectable localization devices show promise for improving surgical guidance of nonpalpable breast tumors. [ABSTRACT FROM AUTHOR]

Pancreatic cancer (PC) remains the predominant type of upper gastrointestinal tract cancer, associated with heightened morbidity and a survival rate below 12%. While immunotherapy has brought about transformative changes in the standards of care for most solid tumors, its application in PC is hindered by the ''cold tumor'' microenvironment, marked by the presence of immunosuppressive cells. Modest response rates in PC are attributed, in part to, the fibrotic stroma that obstructs the delivery of systemic immunotherapy. Furthermore, the occurrence of immune-related adverse events (iRAEs) often necessitates the use of sub-therapeutic doses or treatment discontinuation. In the pursuit of innovative approaches to enhance the effectiveness of immunotherapy for PC, implantable drug delivery devices and scaffolds emerge as promising strategies. These technologies offer the potential for sustained drug delivery directly to the tumor site, overcoming stromal barriers, immunosuppression, T cell exclusion, immunotherapy resistance, optimizing drug dosage, and mitigating systemic toxicity. This review offers a comprehensive exploration of pancreatic ductal adenocarcinoma (PDAC), the most common and aggressive form of PC, accompanied by a critical analysis of the challenges the microenvironment presents to the development of successful combinational immunotherapy approaches. Despite efforts, these approaches have thus far fallen short in enhancing treatment outcomes for PDAC. The review will subsequently delve into the imperative need for refining delivery strategies, providing an examination of past and ongoing studies in the field of localized immunotherapy for PDAC. Addressing these issues will lay the groundwork for the development of effective new therapies, thereby enhancing treatment response, patient survival, and overall quality of life for individuals diagnosed with PDAC. [Display omitted] [ABSTRACT FROM AUTHOR]

Objective: Focal cooling is emerging as a relevant therapy for drug‐resistant epilepsy (DRE). However, we lack data on its effectiveness in controlling seizures that originate in deep‐seated areas like the hippocampus. We present a thermoelectric solution for focal brain cooling that specifically targets these brain structures. Methods: A prototype implantable device was developed, including temperature sensors and a cannula for penicillin injection to create an epileptogenic zone (EZ) near the cooling tip in a non‐human primate model of epilepsy. The mesial temporal lobe was targeted with repeated penicillin injections into the hippocampus. Signals were recorded from an sEEG (Stereoelectroencephalography) lead placed 2 mm from the EZ. Once the number of seizures had stabilized, focal cooling was applied, and temperature and electroclinical events were monitored using a customized detection algorithm. Tests were performed on two Macaca fascicularis monkeys at three temperatures. Results: Hippocampal seizures were observed 40–120 min post‐injection, their duration and frequency stabilized at around 120 min. Compared to the control condition, a reduction in the number of hippocampal seizures was observed with cooling to 21°C (Control: 4.34 seizures, SD 1.704 per 20 min vs Cooling to 21°C: 1.38 seizures, SD 1.004 per 20 min). The effect was more pronounced with cooling to 17°C, resulting in an almost 80% reduction in seizure frequency. Seizure duration and number of interictal discharges were unchanged following focal cooling. After several months of repeated penicillin injections, hippocampal sclerosis was observed, similar to that recorded in humans. In addition, seizures were identified by detecting temperature variations of 0.3°C in the EZ correlated with the start of the seizures. Significance: In epilepsy therapy, the ultimate aim is total seizure control with minimal side effects. Focal cooling of the EZ could offer an alternative to surgery and to existing neuromodulation devices. [ABSTRACT FROM AUTHOR]

Automated drug delivery systems (ADDS) improve chronic disease management by enhancing adherence and reducing patient burden, particularly in conditions like type 1 diabetes, through intraperitoneal insulin delivery. However, periodic invasive refilling of the reservoir is needed in such a class of implantable devices. In previous work, an implantable ADDS with a capsule docking system is introduced for non‐invasive reservoir refilling. Yet, it encounters reliability issues in manufacturing, sealing, and docking design and lacks evidence on intestinal tissue compression effects and chronic in vivo data. This work proposes an optimization of the different components featuring this ADDS. The ingestible capsule is designed, developed, and tested following ISO 13485, exhibiting high insulin stability and optimal sealing for six days in harsh gastrointestinal‐like conditions. A magnetic docking system is optimized, ensuring reliable and stable capsule docking at a clinically relevant distance of 5.92 mm. Histological tests on human intestinal tissues confirm safe capsule compression during docking. Bench tests demonstrate that the integrated mechatronic system effectively docks capsules at various peristalsis‐mimicking velocities. A six‐week in vivo test on porcine models demonstrates chronic safety and provides hints on fibrotic reactions. These results pave the way for the further evolution of implantable ADDS.

Chronic venous insufficiency (CVI) is increasing in prevalence on a global scale. Current treatment options are limited to improving venous return, ablation of refluxing veins, and reducing outflow obstruction. A new bioprosthetic device, the VenoValve, may bridge the gap of treatment for patients with chronic venous insufficiency who have failed prior treatment. We demonstrate the treatment of a 72-year-old man with bilateral venous insufficiency and leg wounds using this device in his left femoral vein via an open anterior surgical approach. The patient had no postoperative complications, and a patent valve at 6 months. The VenoValve may be a viable option for patients with advanced chronic venous insufficiency.

An artificial retina featuring bionic vision processing is presented as a paradigm shift of metaverse. The main contribution is to provide a methodology to better understand the human vision and to reproduce images along the visual pathway. Simulation results include retinal images, bilateral neural images, depth maps, etc. [ABSTRACT FROM AUTHOR]

Background/Aims: An implantable cardioverter defibrillator (ICD) can deliver a shock that converts a dangerously abnormal heart rhythm into a safe rhythm, preventing a sudden cardiac death. However, the transition from life without an ICD to life with one can be challenging. This study aimed to explore how patients perceived the transition process to life with an ICD. Methods: This qualitative descriptive study was conducted with 10 patients with ICDs, recruited from a tertiary hospital in the Republic of Ireland. A semi-structured interview guide was used to conduct in-person interviews at the end of 2016. The transcripts were thematically analysed, with transition theory being used as a framework to support the process. Results: Participants described how the ICD meant that they had to adapt to a new way of living, with physical, psychological and lifestyle adjustments. The transition process was neither immediate nor linear. Fear of defibrillation and receipt of shocks caused feelings of vulnerability, while the loss of a driving license was perceived as a threat to independence. Conclusions: Coping with the aftermath of defibrillator implantation is contingent on education and the level of support offered to patients. Nurses should strive to identify patients' coping and transitioning skills, as they are ideally positioned to initiate timely discussions that are tailored to the individual's needs and capacity. [ABSTRACT FROM AUTHOR]

With the increasing demand in seamless interface between artificial devices and biological structures, flexible bioelectronics has been developed rapidly in recent years. Compared with traditional rigid bioelectronics, flexible devices are more adaptable to the integration for various parts both inside and outside of the organism. Significant achievements have been made in biomedical devices, neuroelectronics and wearable devices. With the development of flexible bioelectronics, electromagnetics is becoming a crucial part in signal interference reduction and information transmission or feedback, taking advantages of strong penetration and rapid response in a variety of biological materials. In this review, we focus on the latest developments in electromagnetic based flexible bioelectronics, involving materials, sensation, seamless integration, and power supply, as well as the latest achievements in the fields of external wearables, internal implants, soft robotics and drug delivery system. Based on these, the main challenges facing flexible bioelectronics, are analyzed, including stretchability caused by mismatch between mechanical properties of soft and hard components, biocompatibility, environmental stability, to facilitate the further development of flexible bioelectronics. [ABSTRACT FROM AUTHOR]

In this study, an analysis of the behavior of the vertebra during the use of KP and SJ was carried out to understand the kinematics of the movement of the fragments of the vertebra during action and the forces generated in the use of the two methods. For this analysis, the results published by various authors were used. Only the principle of the mechanical actuation of the vertebra fragments was analyzed, without addressing other aspects such as the method of cement introduction, the type of cement used, PMMA hardening times, the duration of the operation, the patient's recovery time, etc. In addition to the analysis, the authors propose a device that eliminates the inconveniences observed in the two analyzed devices and promises to significantly improve the restoration of the vertebra's height and, consequently, the patient's symptoms. The observations show that the type of mechanism articulated at one end has both robustness and greater efficiency in this type of actuation. It is further shown that from this category, the mechanism with two arms (Two-Arm Device) proposed by the authors is superior to the existing ones in terms of robustness and efficiency. The perspectives of TAD are represented by the improvement of the vertebral statics and, consequently, the symptoms of the patients. [ABSTRACT FROM AUTHOR]

Monitoring neurochemical signaling across time scales is critical to understanding how brains encode and store information. Flexible (vs stiff) devices have been shown to improve in vivo monitoring, particularly over longer times, by reducing tissue damage and immunological responses. Here, we report our initial steps toward developing flexible and implantable neuroprobes with aptamer-field-effect transistor (FET) biosensors for neurotransmitter monitoring. A high-throughput process was developed to fabricate thin, flexible polyimide probes using microelectromechanical-system (MEMS) technologies, where 150 flexible probes were fabricated on each 4 in. Si wafer. Probes were 150 μm wide and 7 μm thick with two FETs per tip. The bending stiffness was 1.2 × 10-11 N·m2. Semiconductor thin films (3 nm In2O3) were functionalized with DNA aptamers for target recognition, which produces aptamer conformational rearrangements detected via changes in FET conductance. Flexible aptamer-FET neuroprobes detected serotonin at femtomolar concentrations in high-ionic strength artificial cerebrospinal fluid. A straightforward implantation process was developed, where microfabricated Si carrier devices assisted with implantation such that flexible neuroprobes detected physiological relevant serotonin in a tissue-hydrogel brain mimic.

Background: The objective of this study was to design a new wireless left ventricular assist device (LVAD) that can be charged without using a conventional transcutaneous energy transfer system (TETS). Methods: Our new wireless LVAD was a hybrid pump operating in two different modes: magnetic and electric modes. The pump was driven wirelessly by extracorporeal rotating magnets in magnetic mode, whereas it was driven by electricity provided by an intracorporeal battery in electric mode. A magnetic torque transmission system was introduced to wirelessly transmit torque to the pump impeller. The intracorporeal battery was charged in magnetic mode making use of electromagnetic coils as a generator, whereas the coils were used as a motor in electric mode. To demonstrate the feasibility of our system, we conducted a bench‐top durability test for 1 week. Results: Our hybrid pump had shown sufficient pump performance as a LVAD, with a head pressure of approximately 80 mm Hg and a flow volume of 5.0 L/min, for 1 week. The intracorporeal battery was wirelessly charged enough to power electric mode for 2.5 h a day throughout the 1‐week durability test. Conclusions: Our hybrid wireless LVAD system demonstrated the possibility of a wireless LVAD and has the potential to reduce medical complications of LVAD therapy. [ABSTRACT FROM AUTHOR]

In view of inevitable recurrences despite resection, glioblastoma (GB) is still an unmet clinical need. Dealing with the stromal-cell derived factor 1-alpha (SDF-1α)/CXCR4 axis as a hallmark of infiltrative GB tumors and with the resection cavity situation, the present study described the effects and relevance of a new engineered micro-nanostructured SF-HA-Hep aerogel sponges, made of silk fibroin (SF), hyaluronic acid (HA) and heparin (Hep) and loaded with SDF-1α, to interfere with the GB ecosystem and residual GB cells, attracting and confining them in a controlled area before elimination. 70 µm-pore sponges were designed as an implantable scaffold to trap GB cells. They presented shape memory and fit brain cavities. Histological results after implantation in brain immunocompetent Fischer rats revealed that SF-HA-Hep sponges are well tolerated for more than 3 months while moderately and reversibly colonized by immuno-inflammatory cells. The use of human U87MG GB cells overexpressing the CXCR4 receptor (U87MG-CXCR4+) and responding to SDF-1α allowed demonstrating directional GB cell attraction and colonization of the device in vitro and in vivo in orthotopic resection cavities in Nude rats. Not modifying global survival, aerogel sponge implantation strongly shaped U87MG-CXCR4+ tumors in cavities in contrast to random infiltrative growth in controls. Overall, those results support the interest of SF-HA-Hep sponges as modifiers of the GB ecosystem dynamics acting as "cell meeting rooms" and biocompatible niches whose properties deserve to be considered toward the development of new clinical procedures. Brain tumor glioblastoma (GB) is one of the worst unmet clinical needs. To prevent the relapse in the resection cavity situation, new implantable biopolymer aerogel sponges loaded with a chemoattractant molecule were designed and preclinically tested as a prototype targeting the interaction between the initial tumor location and its attraction by the peritumoral environment. While not modifying global survival, biocompatible SDF1-loaded hyaluronic acid and silk fibroin sponges induce directional GB cell attraction and colonization in vitro and in rats in vivo. Interestingly, they strongly shaped GB tumors in contrast to random infiltrative growth in controls. These results provide original findings on application of exogenous engineered niches that shape tumors and serve as cell meeting rooms for further clinical developments. [Display omitted] [ABSTRACT FROM AUTHOR]

Abstract The customizability of 3D printing allows for the manufacturing of personalized medical devices such as laryngectomy tubes, but it is vital to establish the biocompatibility of printing materials to ensure that they are safe and durable. The goal of this study was to assess the presence of S. aureus biofilms on a variety of 3D printed materials (two surgical guide resins, a photopolymer, an elastomer, and a thermoplastic elastomer filament) as compared to standard, commercially available laryngectomy tubes. C-shaped discs (15 mm in height, 20 mm in diameter, and 3 mm in thickness) were printed with five different biocompatible 3D printing materials and S. aureus growth was compared to Shiley™ laryngectomy tubes made from polyvinyl chloride. Discs of each material were inoculated with S. aureus cultures and incubated overnight. All materials were then removed from solution, washed in phosphate-buffered saline to remove planktonic bacteria, and sonicated to detach biofilms. Some solution from each disc was plated and colony-forming units were manually counted the following day. The resulting data was analyzed using a Kruskal-Wallis and Wilcoxon Rank Sum test to determine pairwise significance between the laryngectomy tube material and the 3D printed materials. The Shiley™ tube grew a median of 320 colonies (IQR 140–520), one surgical guide resin grew a median of 640 colonies (IQR 356–920), the photopolymer grew a median of 340 colonies (IQR 95.5–739), the other surgical guide resin grew a median of 431 colonies (IQR 266.5–735), the thermoplastic elastomer filament grew a median of 188 colonies (IQR 113.5–335), and the elastomer grew a median of 478 colonies (IQR 271–630). Using the Wilcoxon Rank Sum test, manual quantification showed a significant difference between biofilm formation only between the Shiley™ tube and a surgical guide resin (p = 0.018). This preliminary study demonstrates that bacterial colonization was comparable among most 3D printed materials as compared to the conventionally manufactured device. Continuation of this work with increased replicates will be necessary to determine which 3D printing materials optimally resist biofilm formation.

We deposited micro‐scale organic light‐emitting diodes(OLEDs) with a red‐emitting material on an ultrathin organic film and demonstrated a flexible device with a cantilever form factor. This platform satisfied the necessary light irradiation conditions applicable for phototherapeutic applications and also holds potential for biomedical implantable areas such as neurotherapy. [ABSTRACT FROM AUTHOR]

Achieving negative surgical margins, defined as no tumor found on the edges of the resected tissue, during lumpectomy for breast cancer is critical for mitigating the risk of local recurrence. To identify nonpalpable tumors that cannot be felt, pre-operative placements of wire and wire-free localization devices are typically employed. Wire-free localization approaches have significant practical advantages over wired techniques. In this study, we introduce an innovative localization system comprising a light-emitting diode (LED)-based implantable device and handheld system. The device, which is needle injectable and wire free, utilizes multiple wirelessly powered LEDs to provide direct visual guidance for lumpectomy. Two distinct colors, red and blue, provide a clear indication of tissue depth: blue light is absorbed strongly in tissue, visible within a close range of 2 cm of ex vivo chicken breast and bovine muscle tissue using less than 4 W of transmitted power from a handheld antenna. These miniaturized needle-injectable localization devices show promise for improving surgical guidance of nonpalpable breast tumors.

Adherence to medication plays a crucial role in the effective management of chronic diseases. However, patients often miss their scheduled drug administrations, resulting in suboptimal disease control. Therefore, we propose an implantable device enabled with automated and precisely timed drug administration. Our device incorporates a built-in mechanical clock movement to utilize a clockwork mechanism, i.e., a periodic turn of the hour axis, enabling automatic drug infusion at precise 12-h intervals. The actuation principle relies on the sophisticated design of the device, where the rotational movement of the hour axis is converted into potential mechanical energy and is abruptly released at the exact moment for drug administration. The clock movement can be charged either automatically by mechanical agitations or manually by winding the crown, while the device remains implanted, thereby enabling the device to be used permanently without the need for batteries. When tested using metoprolol, an antihypertensive drug, in a spontaneously hypertensive animal model, the implanted device can deliver drug automatically at precise 12-h intervals without the need for further attention, leading to similarly effective blood pressure control and ultimately, prevention of ventricular hypertrophy as compared with scheduled drug administrations. These findings suggest that our device is a promising alternative to conventional methods for complex drug administration. [ABSTRACT FROM AUTHOR]

The customizability of 3D printing allows for the manufacturing of personalized medical devices such as laryngectomy tubes, but it is vital to establish the biocompatibility of printing materials to ensure that they are safe and durable. The goal of this study was to assess the presence of S. aureus biofilms on a variety of 3D printed materials (two surgical guide resins, a photopolymer, an elastomer, and a thermoplastic elastomer filament) as compared to standard, commercially available laryngectomy tubes. C-shaped discs (15 mm in height, 20 mm in diameter, and 3 mm in thickness) were printed with five different biocompatible 3D printing materials and S. aureus growth was compared to Shiley™ laryngectomy tubes made from polyvinyl chloride. Discs of each material were inoculated with S. aureus cultures and incubated overnight. All materials were then removed from solution, washed in phosphate-buffered saline to remove planktonic bacteria, and sonicated to detach biofilms. Some solution from each disc was plated and colony-forming units were manually counted the following day. The resulting data was analyzed using a Kruskal-Wallis and Wilcoxon Rank Sum test to determine pairwise significance between the laryngectomy tube material and the 3D printed materials. The Shiley™ tube grew a median of 320 colonies (IQR 140–520), one surgical guide resin grew a median of 640 colonies (IQR 356–920), the photopolymer grew a median of 340 colonies (IQR 95.5–739), the other surgical guide resin grew a median of 431 colonies (IQR 266.5–735), the thermoplastic elastomer filament grew a median of 188 colonies (IQR 113.5–335), and the elastomer grew a median of 478 colonies (IQR 271–630). Using the Wilcoxon Rank Sum test, manual quantification showed a significant difference between biofilm formation only between the Shiley™ tube and a surgical guide resin (p = 0.018). This preliminary study demonstrates that bacterial colonization was comparable among most 3D printed materials as compared to the conventionally manufactured device. Continuation of this work with increased replicates will be necessary to determine which 3D printing materials optimally resist biofilm formation. [ABSTRACT FROM AUTHOR]

Background: Subdural electrocorticography (ECoG) signals have been proposed as a stable, good-quality source for brain-machine interfaces (BMIs), with a higher spatial and temporal resolution than electroencephalography (EEG). However, long-term implantation may lead to chronic inflammatory reactions and connective tissue encapsulation, resulting in a decline in signal recording quality. However, no study has reported the effects of the surrounding tissue on signal recording and device functionality thus far. Methods: In this study, we implanted a wireless recording device with a customized 32-electrode-ECoG array subdurally in two nonhuman primates for 15 months. We evaluated the neural activities recorded from and wirelessly transmitted to the devices and the chronic tissue reactions around the electrodes. In addition, we measured the gain factor of the newly formed ventral fibrous tissue in vivo. Results: Time-frequency analyses of the acute and chronic phases showed similar signal features. The average root mean square voltage and power spectral density showed relatively stable signal quality after chronic implantation. Histological examination revealed thickening of the reactive tissue around the electrode array; however, no evident inflammation in the cortex. From gain factor analysis, we found that tissue proliferation under electrodes reduced the amplitude power of signals. Conclusion: This study suggests that subdural ECoG may provide chronic signal recordings for future clinical applications and neuroscience research. This study also highlights the need to reduce proliferation of reactive tissue ventral to the electrodes to enhance long-term stability. [ABSTRACT FROM AUTHOR]

In this study, an analysis of the behavior of the vertebra during the use of KP and SJ was carried out to understand the kinematics of the movement of the fragments of the vertebra during action and the forces generated in the use of the two methods. For this analysis, the results published by various authors were used. Only the principle of the mechanical actuation of the vertebra fragments was analyzed, without addressing other aspects such as the method of cement introduction, the type of cement used, PMMA hardening times, the duration of the operation, the patient’s recovery time, etc. In addition to the analysis, the authors propose a device that eliminates the inconveniences observed in the two analyzed devices and promises to significantly improve the restoration of the vertebra’s height and, consequently, the patient’s symptoms. The observations show that the type of mechanism articulated at one end has both robustness and greater efficiency in this type of actuation. It is further shown that from this category, the mechanism with two arms (Two-Arm Device) proposed by the authors is superior to the existing ones in terms of robustness and efficiency. The perspectives of TAD are represented by the improvement of the vertebral statics and, consequently, the symptoms of the patients.

In this study, we developed a miniaturized observation system for rat brain imaging using an implantable imager. A small data-acquisition device was designed to be mounted on the back of an adult rat, reducing the disturbance to the output of the imager caused by a long cable. With a weight of approximately 6.8 g, the movement of adult rats with an average weight of 200 g was unrestricted. The readout characteristics were evaluated at the light level. The in vivo experiments were performed using mice and freely moving rats. Using the developed data analysis pipeline, blood flow in the vessels was observed. [ABSTRACT FROM AUTHOR]

Optical and electrophysiological measurements help us understand mouse brain functions. One type of device available for optical measurements is an implantable complementary metaloxide-semiconductor (CMOS) image sensor (ICIS). However, an ICIS alone cannot directly measure the electrical signals emitted by mouse brain neurons. Considering this limitation, we have developed an implantable multimodal sensor that can simultaneously make optical and electrophysiological measurements of the neural activity in the brains of mice. The proposed device integrates a CMOS image sensor and a neural amplifier with a recording electrode into a single chip, making it no more invasive than a conventional implantable CMOS image sensor. The proposed device is based on a 0.35-µm CMOS standard process and occupies an area of 0.50 × 5.0 mm2. Furthermore, a hybrid filter is fabricated on the imaging pixel array to remove the excitation light and selectively detect fluorescence. From electrophysiological measurements, we confirm that the neural amplifier features a mid-band gain of 39 dB from 500 mHz to 4 kHz, which is the bandwidth that includes local field and action potentials. Crosstalk noise is observed because of the digital signal used to control the image sensor. However, in vivo experiments demonstrate that the device is capable of simultaneously measuring and processing optical and electrophysiological signals when the amplitude spectrum has a peak of less than 1 µV. [ABSTRACT FROM AUTHOR]

Local field potentials, the extracellular electrical activities from brain regions, provide clinically relevant information about the status of neurophysiological conditions, including epilepsy. In this study, a 13-channel silicon-based single-shank microelectrode array (MEA) was designed and fabricated to record local field potentials (LFPs) from the different depths of a rat’s brain. A titanium/gold layer was patterned as electrodes on an oxidized silicon substrate, and silicon dioxide was deposited as a passivation layer. The fabricated array was implanted in the somatosensory cortex of the right hemisphere of an anesthetized rat. The developed MEA was interfaced with an OpenBCI Cyton Daisy Biosensing Board to acquire the local field potentials. The LFPs were acquired at three different neurophysiological conditions, including baseline signals, chemically-induced epileptiform discharges, and recovered baseline signals after anti-epileptic drug (AED) administration. Further, time-frequency analyses were performed on the acquired biopotentials to study the difference in spatiotemporal features. The processed signals and time-frequency analyses clearly distinguish between pre-convulsant and post-AED baselines and evoked epileptiform discharges. [ABSTRACT FROM AUTHOR]

In this paper, we present the properties of a communication channel used for implantable devices. The human–body communication (HBC) channel was proposed for data communication in implantable devices. The impulse response was measured using a channel-mimicking model, which mimics electrical losses caused by human body tissues. Furthermore, we compared two types of channel-mimicking models to evaluate their applicability depending on the measurement environment. The resultant impulse responses of the HBC channel showed that HBC does not cause severe changes in the channel properties even when the implantable device is rotated. [ABSTRACT FROM AUTHOR]

Advances in chip-scale photonic-electronic integration are enabling a new generation of foundry-manufacturable implantable silicon neural probes incorporating nanophotonic waveguides and microelectrodes for optogenetic stimulation and electrophysiological recording in neuroscience research. Further extending neural probe functionalities with integrated microfluidics is a direct approach to achieve neurochemical injection and sampling capabilities. In this work, we use two-photon polymerization 3D printing to integrate microfluidic channels onto photonic neural probes, which include silicon nitride nanophotonic waveguides and grating emitters. The customizability of 3D printing enables a unique geometry of microfluidics that conforms to the shape of each neural probe, enabling integration of microfluidics with a variety of existing neural probes while avoiding the complexities of monolithic microfluidics integration. We demonstrate the photonic and fluidic functionalities of the neural probes via fluorescein injection in agarose gel and photoloysis of caged fluorescein in solution and in fixed brain tissue. [ABSTRACT FROM AUTHOR]

This paper presents a 1600-pixel integrated neural stimulator with a correlated double-sampling readout (DSR) circuit for a subretinal prosthesis. The retinal stimulation chip inserted beneath the photoreceptor layer comprises an array of an active pixel sensor (APS) and biphasic pulse shaper. The DSR circuit achieves a high signal-to-noise ratio (SNR) of the APS with a short integration time to simultaneously improve the temporal and spatial resolutions of restored vision. This DSR circuit is adopted along with a 5 × 5-pixel tile, which reduces pixel size and improves the SNR by increasing the area occupied by storage capacitors. Moreover, a low-mismatch reference generator enables a low standard deviation between individual pulse shapers. The 1600-pixel retinal chip, fabricated using the 0.18 μm 1P6M CMOS process, occupies a total area of 4.3 mm × 3.3 mm and dissipates an average power of 3.4 mW; this was demonstrated by determining the stimulus current patterns corresponding to the illuminations of an LCD projector. Experimental results show that the proposed high-density stimulation array chip can achieve a high temporal resolution owing to its short integration time. [ABSTRACT FROM AUTHOR]

Recent findings from the ISCoPe study indicate that, after severe contusion to the spinal cord, edema originating in the spinal cord accumulates and compresses the tissue against the surrounding dura mater, despite decompressive laminectomy. It is hypothesized that this compression results in restricted flow of cerebrospinal fluid (CSF) in the subarachnoid space and central canal and ultimately collapses local vasculature, exacerbating ischemia and secondary injury. Here we developed a surgically mounted osmotic transport device (OTD) that rests on the dura and can osmotically remove excess fluid at the injury site. Tests were performed in 4-h studies immediately following severe (250 kD) contusion at T8 in rats using the OTD. A 3-h treatment with the OTD after 1-h post injury significantly reduced spinal cord edema compared to injured controls. A first approximation mathematical interpretation implies that this modest reduction in edema may be significant enough to relieve compression of local vasculature and restore flow of CSF in the region. In addition, we determined the progression of edema up to 28 days after insult in the rat for the same injury model. Results showed peak edema at 72 h. These preliminary results suggest that incorporating the OTD to operate continuously at the site of injury throughout the critical period of edema progression, the device may significantly improve recovery following contusion spinal cord injury.

For the prolonged, controlled delivery of systemic drugs, we propose an implantable drug-delivery chip (DDC) embedded with pairs of a microchannel and drug-reservoir serving as a drug diffusion barrier and depot, respectively. We pursued a DDC for dual drugs: a main-purpose drug, diclofenac (DF), for systemic exposure, and an antifibrotic drug, tranilast (TR), for local delivery. Thus, the problematic fibrotic tissue formation around the implanted device could be diminished, thereby less hindrance in systemic exposure of DF released from the DDC. First, we separately prepared DDCs for DF or TR delivery, and sought to find a proper microchannel length for a rapid onset and sustained pattern of drug release, as well as the required drug dose. Then, two distinct DDCs for DF and TR delivery, respectively, were assembled to produce a Dual_DDC for the concurrent delivery of DF and TR. When the Dual_DDC was implanted in living rats, the DF concentration in blood plasma did not drop significantly in the later periods after implantation relative to that in the early periods before fibrotic tissue formation. When the Dual_DDC was implanted without TR, there was a significant decrease in the blood plasma DF concentration as the time elapsed after implantation. Biopsied tissues around the Dual_DDC exhibited a significant decrease in the fibrotic capsule thickness and collagen density relative to the Dual_DDC without TR, owing to the effect of the local, sustained release of the TR.

Prompt administration of first‐aid drugs can save lives during medical emergencies such as anaphylaxis and hypoglycemia. However, this is often performed by needle self‐injection, which is not easy for patients under emergency conditions. Therefore, we propose an implantable device capable of on‐demand administration of first‐aid drugs (i.e., the implantable device with a magnetically rotating disk [iMRD]), such as epinephrine and glucagon, via a noninvasive simple application of the magnet from the outside skin (i.e., the external magnet). The iMRD contained a disk embedded with a magnet, as well as multiple drug reservoirs that were sealed with a membrane, which was designed to rotate at a precise angle only when the external magnet was applied. During this rotation, the membrane on a designated single‐drug reservoir was aligned and torn to expose the drug to the outside. When implanted in living animals, the iMRD, actuated by an external magnet, delivers epinephrine and glucagon, similar to conventional subcutaneous needle injections. [ABSTRACT FROM AUTHOR]

Hybrid emission filters, comprising an interference filter and an absorption filter, exhibit high excitation light rejection performance and can act as lensless fluorescent devices. However, it has been challenging to produce them in large batches over a large area. In this study, we propose and demonstrate a method for transferring a Si substrate, on which the hybrid filter is deposited, onto an image sensor by attaching it to the sensor and removing the substrate via plasma etching. Through this method, we can transfer uniform filters onto fine micrometer-sized needle devices and millimeter-sized multisensor chips. Optical evaluation reveals that the hybrid filter emits light in the 500 to 560 nm range, close to the emission region of green fluorescent protein (GFP). Furthermore, by observing the fluorescence emission from the microbeads, a spatial resolution of 12.11 μm is calculated. In vitro experiments confirm that the fabricated device is able to discriminate GFP emission patterns from brain slices. [ABSTRACT FROM AUTHOR]

Abstract Prompt administration of first‐aid drugs can save lives during medical emergencies such as anaphylaxis and hypoglycemia. However, this is often performed by needle self‐injection, which is not easy for patients under emergency conditions. Therefore, we propose an implantable device capable of on‐demand administration of first‐aid drugs (i.e., the implantable device with a magnetically rotating disk [iMRD]), such as epinephrine and glucagon, via a noninvasive simple application of the magnet from the outside skin (i.e., the external magnet). The iMRD contained a disk embedded with a magnet, as well as multiple drug reservoirs that were sealed with a membrane, which was designed to rotate at a precise angle only when the external magnet was applied. During this rotation, the membrane on a designated single‐drug reservoir was aligned and torn to expose the drug to the outside. When implanted in living animals, the iMRD, actuated by an external magnet, delivers epinephrine and glucagon, similar to conventional subcutaneous needle injections.

Agonist CD40 monoclonal antibodies (mAb) is a promising immunotherapeutic agent for cold‐to‐hot tumor immune microenvironment (TIME) conversion. Pancreatic ductal adenocarcinoma (PDAC) is an aggressive and lethal cancer known as an immune desert, and therefore urgently needs more effective treatment. Conventional systemic treatment fails to effectively penetrate the characteristic dense tumor stroma. Here, it is shown that sustained low‐dose intratumoral delivery of CD40 mAb via the nanofluidic drug‐eluting seed (NDES) can modulate the TIME to reduce tumor burden in murine models. NDES achieves tumor reduction at a fourfold lower dosage than systemic treatment while avoiding treatment‐related adverse events. Further, abscopal responses are shown where intratumoral treatment yields growth inhibition in distant untreated tumors. Overall, the NDES is presented as a viable approach to penetrate the PDAC immune barrier in a minimally invasive and effective manner, for the overarching goal of transforming treatment. [ABSTRACT FROM AUTHOR]

This paper presents a programmable neurostimulator 4 × VDD with 7.2 V operating voltage in a 0.18‐μm/1.8 V CMOS process. The output voltage compliance exceeds 6.2 V. A current gain control is designed to adjust bias current. A 5‐bit current mode digital‐to‐analog converter (DAC) is used to set delivered current in current driver. A high output impedance current mirror is designed to guarantee charge balancing. The charge mismatch after biphasic stimulation is about 0.14%. Moreover, current mirrors are turned off after stimulation to decrease power consumption. The headroom voltage is about 1 V for all the voltage drivers and the current mirrors. The proposed neurostimulator occupies 0.95 × 0.95 mm2 with a maximum current range of 0–2000 μA and a power consumption less than 60 μW. [ABSTRACT FROM AUTHOR]

Self-injectable therapy has several advantages in the treatment of metabolic disorders. However, frequent injections with needles impair patient compliance and medication adherence. Therefore, we develop a fully implantable device capable of on-demand administration of self-injection drugs via noninvasive manual button clicks on the outer skin. The device is designed to infuse the drug only at the moment of click actuation, which allows for an accurate and reproducible drug infusion, and also prevents unwanted drug leakage. Using a mechanical means of drug infusion, this implantable device does not contain any electronic compartments or batteries, making it compact, and semi-permanent. When tested in animals, the device can achieve subcutaneous injection-like pharmacokinetic and pharmacodynamic effects for self-injection drugs such as exenatide, insulin, and glucagon. [ABSTRACT FROM AUTHOR]

This paper reviews and analyses the design of popular radio frequency energy harvesting systems and proposes a method to qualitatively and quantitatively analyze their circuit architectures using new square-wave approximation method. This approach helps in simplifying design analysis. Using this analysis, we can establish no load output voltage characteristics, upper limit on rectifier efficiency, and maximum power characteristics of a rectifier. This paper will help guide the design of RF energy harvesting rectifier circuits for radio frequency identification (RFIDs), the Internet of Things (IoTs), wearable, and implantable medical device applications. Different application scenarios are explained in the context of design challenges, and corresponding design considerations are discussed in order to evaluate their performance. The pros and cons of different rectifier topologies are also investigated. In addition to presenting the popular rectifier topologies, new measurement results of these energy harvester topologies, fabricated in 65nm, 130nm and 180nm CMOS technologies are also presented.

Abstract Background The use of stress perfusion-cardiovascular magnetic resonance (CMR) imaging remains limited in patients with implantable devices. The primary goal of the study was to assess the safety, image quality, and the diagnostic value of stress perfusion-CMR in patients with MR-conditional transvenous permanent pacemakers (PPM) or implantable cardioverter-defibrillators (ICD). Methods Consecutive patients with a transvenous PPM or ICD referred for adenosine stress-CMR were enrolled in this single-center longitudinal study. The CMR protocol was performed using a 1.5 T system according to current guidelines while all devices were put in MR-mode. Quality of cine, late-gadolinium-enhancement (LGE), and stress perfusion sequences were assessed. An ischemia burden of ≥ 1.5 segments was considered significant. We assessed the safety, image quality and the occurrence of interference of the magnetic field with the implantable device. In case of ischemia, we also assessed the correlation with the presence of significant coronary lesions on coronary angiography. Results Among 3743 perfusion-CMR examinations, 66 patients had implantable devices (1.7%). Image quality proved diagnostic in 98% of cases. No device damage or malfunction was reported immediately and at 1 year. Fifty patients were continuously paced during CMR. Heart rate and systolic blood pressure remained unchanged during adenosine stress, while diastolic blood pressure decreased (p = 0.007). Six patients (9%) had an ischemia-positive stress CMR and significant coronary stenoses were confirmed by coronary angiography in all cases. Conclusion Stress perfusion-CMR is safe, allows reliable ischemia detection, and provides good diagnostic value.

Abstract Background Chronic tinnitus affects millions of people globally and constitutes the most commonly compensated disability among military service members in the United States. Existing treatment options largely surround helping patients cope with their disease as opposed to directly suppressing tinnitus perception. The current study investigated the efficacy of electrical stimulation of the cochlea on chronic disabling tinnitus. Methods In this single-arm, open-label clinical trial, 22 adult subjects with severe-range asymmetric or unilateral non-pulsatile tinnitus underwent electrical stimulation of the cochlea through use of an extra-cochlear electrode positioned on the cochlear promontory. Each subject underwent 3 stimulation treatments over 3 weeks at 7-day intervals. Tinnitus severity was determined by Tinnitus Handicap Inventory (THI), Tinnitus Functional Index (TFI), and Tinnitus Visual Analog Scale (VAS). Inclusion criteria required subjects have no worse than moderate sensorineural hearing loss determined by pre-enrollment audiometric testing. The primary outcome was nadir post-treatment THI scores, obtained at seven timepoints following electrical stimulation, with clinically significant improvement defined as a decrease of ≥ 7. Results All 22 (100%) subjects experienced clinically significant improvement in the THI during the study period with a mean decrease in scores of − 31 (95% CI − 38 to − 25) from a baseline of 48. Twenty (91%) experienced clinically significant improvement detectable on at least two of the three tinnitus survey instruments and 17 (77%) experienced clinically significant improvement detectable on all three survey instruments (i.e., THI, TFI, and VAS). Eight (36%) subjects reported either complete (THI of 0; n = 3) or near-complete (THI 1–4; n = 5) suppression of their tinnitus following a stimulation session. Thirteen (59%) subjects reported a nadir following stimulation at or below the threshold for “no or slight handicap” on the THI (≤ 16). No adverse events were observed. Conclusions These findings establish the foundation for the development of an extra-cochlear implantable device that delivers electrical stimulation to the cochlea for the treatment of disabling tinnitus. For patients considering device implantation, trans-tympanic cochlear promontory stimulation can facilitate patient selection. Trial Registration ClinicalTrials.gov Identifier: NCT03759834. URL: https://clinicaltrials.gov/ct2/show/NCT03759834

Abstract Agonist CD40 monoclonal antibodies (mAb) is a promising immunotherapeutic agent for cold‐to‐hot tumor immune microenvironment (TIME) conversion. Pancreatic ductal adenocarcinoma (PDAC) is an aggressive and lethal cancer known as an immune desert, and therefore urgently needs more effective treatment. Conventional systemic treatment fails to effectively penetrate the characteristic dense tumor stroma. Here, it is shown that sustained low‐dose intratumoral delivery of CD40 mAb via the nanofluidic drug‐eluting seed (NDES) can modulate the TIME to reduce tumor burden in murine models. NDES achieves tumor reduction at a fourfold lower dosage than systemic treatment while avoiding treatment‐related adverse events. Further, abscopal responses are shown where intratumoral treatment yields growth inhibition in distant untreated tumors. Overall, the NDES is presented as a viable approach to penetrate the PDAC immune barrier in a minimally invasive and effective manner, for the overarching goal of transforming treatment.

This work explores the recent research conducted towards the development of novel classes of devices in wearable and implantable medical applications allowed by the introduction of the soft robotics approach. In the medical field, the need for materials with mechanical properties similar to biological tissues is one of the first considerations that arises to improve comfort and safety in the physical interaction with the human body. Thus, soft robotic devices are expected to be able of accomplishing tasks no traditional rigid systems can do. In this paper, we describe future perspectives and possible routes to address scientific and clinical issues still hampering the accomplishment of ideal solutions in clinical practice.

The greatest medication encapsulation and distribution options have received substantial research on biodegradable natural polymers. For their potential to act as an effective vehicle for site-specific medication delivery in the body, biodegradable nanoparticles (NPs) are attracting more interest. They provide enhanced biocompatibility, and practical release patterns for a variety of medicines to be used in a number of applications. This article has explored the various applications of these particles, including cancer therapy, implantable device, and antioxidant delivery. However, there is still potential to investigate more biodegradable polymers for cutting-edge biological applications. [ABSTRACT FROM AUTHOR]

Electrocorticography signals, the intracranial recording of electrical signatures of the brain, are recorded by non-penetrating planar electrode arrays placed on the cortical surface. Flexible electrode arrays minimize the tissue damage upon implantation. This work shows the design and development of a 32-channel flexible microelectrode array to record electrocorticography signals from the rat's brain. The array was fabricated on a biocompatible flexible polyimide substrate. A titanium/gold layer was patterned as electrodes, and a thin polyimide layer was used for insulation. The fabricated microelectrode array was mounted on the exposed somatosensory cortex of the right hemisphere of a rat after craniotomy and incision of the dura. The signals were recorded using OpenBCI Cyton Daisy Biosensing Boards. The array faithfully recorded the baseline electrocorticography signals, the induced epileptic activities after applying a convulsant, and the recovered baseline signals after applying an antiepileptic drug. The signals recorded by such fabricated microelectrode array from anesthetized rats demonstrate its potential to monitor electrical signatures corresponding to epilepsy. Finally, the time–frequency analyses highlight the difference in spatiotemporal features of baseline and evoked epileptic discharges. [ABSTRACT FROM AUTHOR]

A wirelessly powered four-channel neurostimulator was developed for applying selective Functional Electrical Stimulation (FES) to four peripheral nerves to control the ankle and knee joints of a rat. The power of the neurostimulator was wirelessly supplied from a transmitter device, and the four nerves were connected to the receiver device, which controlled the ankle and knee joints in the rat. The receiver device had functions to detect the frequency of the transmitter signal from the transmitter coil. The stimulation site of the nerves was selected according to the frequency of the transmitter signal. The rat toe position was controlled by changing the angles of the ankle and knee joints. The joint angles were controlled by the stimulation current applied to each nerve independently. The stimulation currents were adjusted by the Proportional Integral Differential (PID) and feed-forward control method through a visual feedback control system, and the walking trajectory of a rat's hind leg was reconstructed. This study contributes to controlling the multiple joints of a leg and reconstructing functional motions such as walking using the robotic control technology. [ABSTRACT FROM AUTHOR]