Schizophrenia is a severe mental disorder that affects millions of people worldwide. Several atypical antipsychotic medications, including paliperidone (PPD), has been developed and proven effective in treating it. To date, four PPD extended-release products have been launched commercially, providing up to six months of therapeutic effect with a single administration. However, the need for hospital injections by professional healthcare workers not only lead to poor patients\' adherence, but also put additional pressure on the healthcare system. Therefore, three PPD microarray patch (PPD MAP) systems based on dissolving microneedle technology and implantable microneedle technology were developed in this work. The two dissolving microarray patch systems contained either PPD crude drug (PPD DMAP-CD) or PPD nanocrystal (PPD DMAP-NC) and the implantable MAP contained PPD crude drug (PPD IMAP). All three types of PPD MAPs showed excellent mechanical and insertion properties as they achieved over 256 µm insertion depth in skin model. In vitro release study showed that PPD released from IMAP in a much more sustained manner (up to 14 days) than PPD did from DMAPs (7 days), with only 20 % initial burst release from IMAP compared with 43-71 % from DMAPs. The MAP dissolution study showed that both DMAPs can be immediately dissolved within less than 3 min once inserted into the skin, indicating a faster action potential compared with IMAP. Ex vivo delivery study showed that 1.68 ± 0.23 mg, 1.39 ± 0.07 mg, and 1.18 ± 0.12 mg were delivered from DMAP-CD, DMAP-NC and IMAP, respectively, demonstrating that over 50 % and up to 70 % of PPD in the MAPs can be delivered into the skin. The IMAP offers most sustained release of PPD whereas DMAP-NC exhibits fastest PPD release (11.19 % vs 20.01 % into Franz cell receiver compartment over 24 h). This work presents a promising alternative for the sustained delivery of antipsychotic drugs, allowing for patient self-administration and extended release concurrently. Patients may potentially use both DMAP and IMAP to achieve a sustained release of PPD while also avoid having an initial therapeutic lag.

In the relentless pursuit of precision medicine, the intersection of cutting-edge technology and healthcare has given rise to a transformative era. At the forefront of this revolution stands the burgeoning field of wearable and implantable biosensors, promising a paradigm shift in how we monitor, analyze, and tailor medical interventions. As these miniature marvels seamlessly integrate with the human body, they weave a tapestry of real-time health data, offering unprecedented insights into individual physiological landscapes. This log embarks on a journey into the realm of wearable and implantable biosensors, where the convergence of biology and technology heralds a new dawn in personalized healthcare. Here, we explore the intricate web of innovations, challenges, and the immense potential these bioelectronics sentinels hold in sculpting the future of precision medicine.

Implantable devices are vital in healthcare, enabling continuous monitoring, early disease detection, informed decision-making, enhanced outcomes, cost reduction, and chronic condition management. These devices provide real-time data, allowing proactive healthcare interventions, and contribute to overall improvements in patient care and quality of life. The success of implantable devices relies on the careful selection of materials and manufacturing methods. Recent materials research and manufacturing advancements have yielded implantable devices with enhanced biocompatibility, reliability, and functionality, benefiting human healthcare. This paper provides a comprehensive overview of the latest developments in implantable medical devices, emphasizing the importance of material selection and manufacturing methods, including biocompatibility, self-healing capabilities, corrosion resistance, mechanical properties, and conductivity. It explores various manufacturing techniques such as microfabrication, 3D printing, laser micromachining, electrospinning, screen printing, inkjet printing, and nanofabrication. The paper also discusses challenges and limitations in the field, including biocompatibility concerns, privacy and data security issues, and regulatory hurdles for implantable devices.

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Poly(3, 4-ethylenedioxythiophene) (PEDOT) as a new generation of intelligent conductive polymers, is attracting much attention in the field of tissue engineering. However, its water dispersibility, conductivity, and biocompatibility are incompatible, which limit its further development. In this work, biocompatible electrode material of PEDOT doped with sodium sulfonated alginate (SS) which contains two functional groups of sulfonic acid and carboxylic acid per repeat unit of the macromolecule. The as dual-site doping strategy simultaneously boosts anticoagulant and electrochemical performances, for example, good hydrophilicity (water contact angle of 59.40°), well dispersibility (dispersion solution unstratified in 30 days), high conductivity (4.45 S m-1), and enhanced anticoagulant property (extended activated partial thrombin time value of 59.0 s), forming an adjustable PEDOT: biomacromolecule interface; this fills the technical gap of implantable bioelectronics in terms of coagulation and thrombosis risk. At the same time, the assembled all-in-one supercapacitor with anticoagulant properties is prepared by PEDOT: sodium sulfonated alginate as electrode material and sodium alginate hydrogel as electrolyte layer. The dual-site doping strategy provides a new opinion for the design and optimization of functional conductive polymers and its applications in implantable energy storage fields.

Pediatric patients who undergo implant insertion into the chest wall face a high risk of implant exposure to the external environment. Five months after an 8-year-old boy underwent implantable cardioverter-defibrillator (ICD) implantation in a subcutaneous pocket in the left anterolateral chest wall to manage long QT syndrome, ICD replacement became necessary owing to exposure risk from distal and lateral thinning of the ICD pocket. Pocket rupture and exposure would increase the risk of infection; therefore, we performed ICD removal and primary pocket closure. Two weeks later, a new suprafascial pocket was created, an acellular dermal matrix (ADM) was attached to the inner wall to prevent ICD protrusion, and a new ICD was inserted. One year postoperatively, the ADM was engrafted, and no complications were observed. A thin subcutaneous layer increases the risk of ICD implantation complications. Inner wall strengthening with an ADM can help prevent pocket rupture.

Dopamine (DA) and serotonin (5-HT) are neurotransmitters that regulate a wide range of physiological and behavioral processes. Monitoring of both neurotransmitters with real-time analysis offers important insight into the mechanisms that shape animal behavior. However, bioelectronic tools to simultaneously monitor DA and 5-HT interactive dynamics in freely moving animals are underdeveloped. This is mainly due to the limited sensor sensitivity with miniaturized electronics. Here, we present a semi-implantable electrochemical device achieved by integrating a multi-surface-modified carbon fiber microelectrode with a miniaturized potentiostat module to detect DA and 5-HT in vivo with high sensitivity and selectivity. Specifically, carbon fiber microelectrodes were modified through electrochemical treatment and surface coatings to improve sensitivity, selectivity, and antifouling properties. A customized, lightweight potentiostat module was developed for untethered electrochemical measurements. Integrated with the microelectrode, the microsystem is compact (2.8 × 2.3 × 2.1 cm) to minimize its impacts on animal behavior and achieved simultaneous detection of DA and 5-HT with sensitivities of 48.4 and 133.0 nA/μM, respectively, within submicromolar ranges. The system was attached to the crayfish dorsal carapace, allowing electrode implantation into the heart of a crayfish to monitor DA and 5-HT dynamics, followed by drug injections. The semi-implantable biosensor system displayed a significant increase in oxidation peak currents after DA and 5-HT injections. The device successfully demonstrated the application for in vivo simultaneous monitoring of DA and 5-HT in the hemolymph (i.e., blood) of freely behaving crayfish underwater, yielding a valuable experimental tool to expand our understanding of the comodulation of DA and 5-HT.

Implantable bioelectronics, integrated directly within the body, represent a potent biomedical solution for monitoring and treating a range of medical conditions, including chronic diseases, neural disorders, and cardiac conditions, through personalized medical interventions. Nevertheless, contemporary implantable bioelectronics rely heavily on rigid materials (e.g., inorganic materials and metals), leading to inflammatory responses and tissue damage due to a mechanical mismatch with biological tissues. Recently, soft electronics with mechanical properties comparable to those of biological tissues have been introduced to alleviate fatal immune responses and improve tissue conformity. Despite their myriad advantages, substantial challenges persist in surgical handling and precise positioning due to their high compliance. To surmount these obstacles, softening implantable bioelectronics has garnered significant attention as it embraces the benefits of both rigid and soft bioelectronics. These devices are rigid for easy standalone implantation, transitioning to a soft state in vivo in response to environmental stimuli, which effectively overcomes functional/biological problems inherent in the static mechanical properties of conventional implants. This article reviews recent research and development in softening materials and designs for implantable bioelectronics. Examples featuring tissue-penetrating and conformal softening devices highlight the promising potential of these approaches in biomedical applications. A concluding section delves into current challenges and outlines future directions for softening implantable device technologies, underscoring their pivotal role in propelling the evolution of next-generation bioelectronics.

Implantable biosensors have evolved to the cutting-edge technology of personalized health care and provide promise for future directions in precision medicine. This is the reason why these devices stand to revolutionize our approach to health and disease management and offer insights into our bodily functions in ways that have never been possible before. This review article tries to delve into the important developments, new materials, and multifarious applications of these biosensors, along with a frank discussion on the challenges that the devices will face in their clinical deployment. In addition, techniques that have been employed for the improvement of the sensitivity and specificity of the biosensors alike are focused on in this article, like new biomarkers and advanced computational and data communicational models. A significant challenge of miniaturized in situ implants is that they need to be removed after serving their purpose. Surgical expulsion provokes discomfort to patients, potentially leading to post-operative complications. Therefore, the biodegradability of implants is an alternative method for removal through natural biological processes. This includes biocompatible materials to develop sensors that remain in the body over longer periods with a much-reduced immune response and better device longevity. However, the biodegradability of implantable sensors is still in its infancy compared to conventional non-biodegradable ones. Sensor design, morphology, fabrication, power, electronics, and data transmission all play a pivotal role in developing medically approved implantable biodegradable biosensors. Advanced material science and nanotechnology extended the capacity of different research groups to implement novel courses of action to design implantable and biodegradable sensor components. But the actualization of such potential for the transformative nature of the health sector, in the first place, will have to surmount the challenges related to biofouling, managing power, guaranteeing data security, and meeting today\'s rules and regulations. Solving these problems will, therefore, not only enhance the performance and reliability of implantable biodegradable biosensors but also facilitate the translation of laboratory development into clinics, serving patients worldwide in their better disease management and personalized therapeutic interventions.

Background: Cardiac resynchronization therapy (CRT) has evolved into an established therapy for patients with chronic heart failure and a wide QRS complex. Data on long-term outcomes over time are scarce and the criteria for implantation remain a subject of investigation. Methods: An international, multicenter, retrospective registry includes 2275 patients who received CRT between 30 November 2000 and 31 December 2019, with a mean follow-up of 3.6 ± 2.7 years. Four time periods were defined, based on landmark trials and guidelines. The combined endpoint was a composite of all-cause mortality, heart transplantation, or left ventricular assist device implantation. Results: The composite endpoint occurred in 656 patients (29.2%). The mean annual implantation rate tripled from 31.5 ± 17.4/year in the first period to 107.4 ± 62.4/year in the last period. In the adjusted Cox regression analysis, the hazard ratio for the composite endpoint was not statistically different between time periods. When compared to sinus rhythm with left bundle branch block (LBBB), a non-LBBB conduction pattern (sinus rhythm: HR 1.51, 95% CI 1.12-2.03; atrial fibrillation: HR 2.08, 95% CI 1.30-3.33) and a QRS duration below 130 ms (HR 1.64, 95% CI 1.29-2.09) were associated with a higher hazard ratio. Conclusions: Despite innovations, an adjusted regression analysis revealed stable overall survival over time, which can at least partially be explained by a shift in patient characteristics.