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Cardiovascular diseases (CVDs) are a predominant global health concern, accounting for over 17.9 million deaths in 2019, representing approximately 32% of all global fatalities. In North America and Europe, over a million adults undergo cardiac surgeries annually. Despite the benefits, such surgeries pose risks and require precise postsurgery monitoring. However, during the postdischarge period, where monitoring infrastructures are limited, continuous monitoring of vital signals is hindered. In this area, the introduction of implantable electronics is altering medical practices by enabling real-time and out-of-hospital monitoring of physiological signals and biological information postsurgery. The multimodal implantable bioelectronic platforms have the capability of continuous heart sensing and stimulation, in both postsurgery and out-of-hospital settings. Furthermore, with the emergence of machine learning algorithms into healthcare devices, next-generation implantables will benefit artificial intelligence (AI) and connectivity with skin-interfaced electronics to provide more precise and user-specific results. This Review outlines recent advancements in implantable bioelectronics and their utilization in cardiovascular health monitoring, highlighting their transformative deployment in sensing and stimulation to the heart toward reaching truly personalized healthcare platforms compatible with the Sustainable Development Goal 3.4 of the WHO 2030 observatory roadmap. This Review also discusses the challenges and future prospects of these devices.

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Wearable and implantable sensing of biomechanical signals such as pressure, strain, shear, and vibration can enable a multitude of human-integrated applications, including on-skin monitoring of vital signs, motion tracking, monitoring of internal organ condition, restoration of lost/impaired mechanoreception, among many others. The mechanical conformability of such sensors to the human skin and tissue is critical to enhancing their biocompatibility and sensing accuracy. As such, in the recent decade, significant efforts have been made in the development of soft mechanical sensors. To satisfy the requirements of different wearable and implantable applications, such sensors have been imparted with various additional properties to make them better suited for the varied contexts of human-integrated applications. In this review, focusing on the four major types of soft mechanical sensors for pressure, strain, shear, and vibration, we discussed the recent material and device design innovations for achieving several important properties, including flexibility and stretchability, bioresorbability and biodegradability, self-healing properties, breathability, transparency, wireless communication capabilities, and high-density integration. We then went on to discuss the current research state of the use of such novel soft mechanical sensors in wearable and implantable applications, based on which future research needs were further discussed. This article is categorized under: Diagnostic Tools > Biosensing Diagnostic Tools > Diagnostic Nanodevices Implantable Materials and Surgical Technologies > Nanomaterials and Implants.

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Accurate postoperative assessment of varying mechanical properties is crucial for customizing patient-specific treatments and optimizing rehabilitation strategies following Achilles tendon (AT) rupture and reconstruction surgery. This study introduces a wireless, chip-less, and immune-tolerant in vivo strain-sensing suture designed to continuously monitor mechanical stiffness variations in the reconstructed AT throughout the healing process. This innovative sensing suture integrates a standard medical suturing thread with a wireless fiber strain-sensing system, which incorporates a fiber strain sensor and a double-layered inductive coil for wireless readout. The winding design of Au nanoparticle-based fiber electrodes and a hollow core contribute to the fiber strain sensor's high sensitivity (factor of 6.2 and 15.1 pF for revised sensitivity), negligible hysteresis, and durability over 10,000 stretching cycles. To ensure biocompatibility and immune tolerance during extended in vivo periods, an antibiofouling lubricant layer was applied to the sensing suture. Using this sensing system, we successfully monitored the strain responses of the reconstructed AT in an in vivo porcine model. This facilitated the postoperative assessment of mechanical stiffness variations through a well-established analytical model during the healing period.

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Minimally invasive microneedle (MN) is an emerging technology platform for wearable and implantable diagnostics and therapeutics systems. These short MNs offer pain-free insertion and simple operation. Among the MN technologies proposed to enhance interstitial fluid (ISF) extraction, porous and swellable (P-S) hydrogels absorb analyte molecules across the entire lateral surface. Currently, the design, development, and optimization of the MNs rely on empirical, iterative approaches. Based on theory of fluid flow and analyte diffusion through geometrically complex biomimetic systems, here we derive a generalized physics-guided model for P-S MN sensors. The framework (a) quantifies MN extracting efficiency [Formula: see text] in terms of its geometric and physical properties, and (b) suggests strategies to optimize sensor response while satisfying the mechanical constraints related to various skin-types (e.g., mouse, pig, humans, etc.). Our results show that, despite the differences in geometry and composition, P-S MNs obey a universal scaling response, [Formula: see text] with [Formula: see text] being MN length, diffusivity, and radius, respectively, and [Formula: see text], [Formula: see text] and [Formula: see text] are the ratio between approximate vs. exact analytical solutions, the effective biofluid transfer coefficient between dermis and skin, and the exponent for the power-law approximation, respectively. These parameters quantify the biomolecule transfer through the dermis-to-MN interface at different scaling limits. P-S MNs outperform hollow MNs by a 2-6x enhancement factor; however, the buckling-limit of insertion defines the maximized functionality of the sensor. Our model, validated against experimental results and numerical simulations, offers a predictive design framework to significantly reduce the optimization time for P-S MN-based sensor platforms.

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In vivo monitoring of animal physiological information plays a crucial role in promptly alerting humans to potential diseases in animals and aiding in the exploration of mechanisms underlying human diseases. Currently, implantable electrochemical microsensors have emerged as a prominent area of research. These microsensors not only fulfill the technical requirements for monitoring animal physiological information but also offer an ideal platform for integration. They have been extensively studied for their ability to monitor animal physiological information in a minimally invasive manner, characterized by their bloodless, painless features, and exceptional performance. The development of implantable electrochemical microsensors for in vivo monitoring of animal physiological information has witnessed significant scientific and technological advancements through dedicated efforts. This review commenced with a comprehensive discussion of the construction of microsensors, including the materials utilized and the methods employed for fabrication. Following this, we proceeded to explore the various implantation technologies employed for electrochemical microsensors. In addition, a comprehensive overview was provided of the various applications of implantable electrochemical microsensors, specifically in the monitoring of diseases and the investigation of disease mechanisms. Lastly, a concise conclusion was conducted on the recent advancements and significant obstacles pertaining to the practical implementation of implantable electrochemical microsensors.

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Glaucoma, marked by its intricate association with intraocular pressure (IOP), stands as a predominant cause of non-reversible vision loss. In this review, the physiological relevance of IOP is detailed, alongside its potential pathological consequences. The review further delves into innovative engineering solutions for IOP monitoring, highlighting the latest advancements in wearable and implantable sensors and their potential in enhancing glaucoma management. These technological innovations are interwoven with clinical practice, underscoring their real-world applications, patient-centered strategies, and the prospects for future development in IOP control. By synthesizing theoretical concepts, technological innovations, and practical clinical insights, this review contributes a cohesive and comprehensive perspective on the IOP biosensor's role in glaucoma, serving as a reference for ophthalmological researchers, clinicians, and professionals.

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The fourth industrial revolution has led to the development and application of health monitoring sensors that are characterized by digitalization and intelligence. These sensors have extensive applications in medical care, personal health management, elderly care, sports, and other fields, providing people with more convenient and real-time health services. However, these sensors face limitations such as noise and drift, difficulty in extracting useful information from large amounts of data, and lack of feedback or control signals. The development of artificial intelligence has provided powerful tools and algorithms for data processing and analysis, enabling intelligent health monitoring, and achieving high-precision predictions and decisions. By integrating the Internet of Things, artificial intelligence, and health monitoring sensors, it becomes possible to realize a closed-loop system with the functions of real-time monitoring, data collection, online analysis, diagnosis, and treatment recommendations. This review focuses on the development of healthcare artificial sensors enhanced by intelligent technologies from the aspects of materials, device structure, system integration, and application scenarios. Specifically, this review first introduces the great advances in wearable sensors for monitoring respiration rate, heart rate, pulse, sweat, and tears; implantable sensors for cardiovascular care, nerve signal acquisition, and neurotransmitter monitoring; soft wearable electronics for precise therapy. Then, the recent advances in volatile organic compound detection are highlighted. Next, the current developments of human-machine interfaces, AI-enhanced multimode sensors, and AI-enhanced self-sustainable systems are reviewed. Last, a perspective on future directions for further research development is also provided. In summary, the fusion of artificial intelligence and artificial sensors will provide more intelligent, convenient, and secure services for next-generation healthcare and biomedical applications.

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Cardiovascular disease (CVD) causes significant mortality and remains the leading cause of death globally. Thus, to reduce mortality, early diagnosis by measurement of cardiac biomarkers and heartbeat signals presents fundamental importance. Traditional CVD examination requires bulky hospital instruments to conduct electrocardiography recording and immunoassay analysis, which are both time-consuming and inconvenient. Recently, development of biosensing technologies for rapid CVD marker screening attracted great attention. Thanks to the advancement in nanotechnology and bioelectronics, novel biosensor platforms are developed to achieve rapid detection, accurate quantification, and continuous monitoring throughout disease progression. A variety of sensing methodologies using chemical, electrochemical, optical, and electromechanical means are explored. This review first discusses the prevalence and common categories of CVD. Then, heartbeat signals and cardiac blood-based biomarkers that are widely employed in clinic, as well as their utilizations for disease prognosis, are summarized. Emerging CVD wearable and implantable biosensors and monitoring bioelectronics, allowing these cardiac markers to be continuously measured are introduced. Finally, comparisons of the pros and cons of these biosensing devices along with perspectives on future CVD biosensor research are presented.

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Recording brain neural signals and optogenetic neuromodulations open frontiers in decoding brain neural information and neurodegenerative disease therapeutics. Conventional implantable probes suffer from modulus mismatch with biological tissues and an irreconcilable tradeoff between transparency and electron conductivity. Herein, a strategy is proposed to address these tradeoffs, which generates conductive and transparent hydrogels with polypyrrole-decorated microgels as cross-linkers. The optical transparency of the electrodes can be attributed to the special structures that allow light waves to bypass the microgel particles and minimize their interaction. Demonstrated by probing the hippocampus of rat brains, the biomimetic electrode shows a prolonged capacity for simultaneous optogenetic neuromodulation and recording of brain neural signals. More importantly, an intriguing brain-machine interaction is realized, which involves signal input to the brain, brain neural signal generation, and controlling limb behaviors. This breakthrough work represents a significant scientific advancement toward decoding brain neural information and developing neurodegenerative disease therapies.

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The intersection of biomedicine and radio frequency (RF) engineering has fundamentally transformed self-health monitoring by leveraging soft and wearable electronic devices. This paradigm shift presents a critical challenge, requiring these devices and systems to possess exceptional flexibility, biocompatibility, and functionality. To meet these requirements, traditional electronic systems, such as sensors and antennas made from rigid and bulky materials, must be adapted through material science and schematic design. Notably, in recent years, extensive research efforts have focused on this field, and this review article will concentrate on recent advancements. We will explore the traditional/emerging materials for highly flexible and electrically efficient wearable electronics, followed by systematic designs for improved functionality and performance. Additionally, we will briefly overview several remarkable applications of wearable electronics in biomedical sensing. Finally, we provide an outlook on potential future directions in this developing area.

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Implantable optical sensors are emerging tools that have the potential to enable constant real-time monitoring of various internal physiological parameters. Such a possibility will open new horizons for health control not only in medicine, but also in animal husbandry, including aquaculture. In this study, we analyze different organs of commonly farmed rainbow trout (Oncorhynchus mykiss) as implantation sites for fluorescent sensors and propose the adipose fin, lacking an endoskeleton, as the optimal choice. The fin is highly translucent due to significantly thinner dermis, which makes the detectable fluorescence of an implanted sensor operating at the visible light range by more than an order of magnitude higher relative to the skin. Compared to the proximal parts of ray fins, the adipose fin provides easy implantation and visualization of the sensor. Finally, we tested fluorescent pH sensors inside the adipose fin and demonstrated the possibility of acquiring their signal with a simple hand-held device and without fish anesthesia. All these features will most likely make the adipose fin the main "window" into the internal physiological processes of salmonid fish with the help of implantable optical sensors.

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Recording electrophysiological information such as brain neural signals is of great importance in health monitoring and disease diagnosis. However, foreign body response and performance loss over time are major challenges stemming from the chemomechanical mismatch between sensors and tissues. Herein, microgels are utilized as large crosslinking centers in hydrogel networks to modulate the tradeoff between modulus and fatigue resistance/stretchability for producing hydrogels that closely match chemomechanical properties of neural tissues. The hydrogels exhibit notably different characteristics compared to nanoparticles reinforced hydrogels. The hydrogels exhibit relatively low modulus, good stretchability, and outstanding fatigue resistance. It is demonstrated that the hydrogels are well suited for fashioning into wearable and implantable sensors that can obtain physiological pressure signals, record the local field potentials in rat brains, and transmit signals through the injured peripheral nerves of rats. The hydrogels exhibit good chemomechanical match to tissues, negligible foreign body response, and minimal signal attenuation over an extended time, and as such is successfully demonstrated for use as long-term implantable sensory devices. This work facilitates a deeper understanding of biohybrid interfaces, while also advancing the technical design concepts for implantable neural probes that efficiently obtain physiological information.

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Macroporous hydrogels are an attractive platform for implantable sensors because the network of interconnected macropores facilitates tissue integration. Embedded sensing elements, in our case, plasmonic gold nanoparticles, can transduce the presence, absence, and concentration of biochemical markers to the outside. We present here how to integrate such nanosensors into a macroporous hydrogel while preserving the nanosensor functionality in order to produce implantable sensors. We demonstrate that out of four different polymers, the poly(2-hydroxyethyl methacrylate-poly(ethylene glycole)diacrylate copolymer (pHEMA-PEGDA) results in a working sensor. Our approach of incorporating nanosized sensor elements into a hydrogel matrix generally identifies suitable polymers for implantable sensor systems.

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Optical biosensing is being actively investigated for minimally-invasive monitoring of key biomarkers both in vitro and in vivo. However, typical benchtop instruments are not portable and are not well suited to high-throughput, real-time analysis. This paper presents a versatile multichannel instrument for measurement of emission intensity and lifetime values arising from luminescent biosensor materials. A detailed design description of the opto-electronic hardware as well as the control software is provided, elaborating a flexible, user-configurable system that may be customized or duplicated for a wide range of applications. This article presents experimental measurements that prove the in vitro and in vivo functionality of the system. Such tools may be adopted for many research and development purposes, including evaluation of new biosensor materials, and may also serve as prototypes for future miniaturized handheld or wearable devices.

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With the recent great progress made in flexible and wearable electronic materials, the upcoming next generation of skin-mountable and implantable smart devices holds extensive potential applications for the lifestyle modifying, including personalized health monitoring, human-machine interfaces, soft robots, and implantable biomedical devices. As a core member within the wearable electronics family, flexible strain sensors play an essential role in the structure design and functional optimization. To further enhance the stretchability, flexibility, sensitivity, and electricity performances of the flexible strain sensors, enormous efforts have been done covering the materials design, manufacturing approaches and various applications. Thus, this review summarizes the latest advances in flexible strain sensors over recent years from the material, application, and manufacturing strategies. Firstly, the critical parameters measuring the performances of flexible strain sensors and materials development contains different flexible substrates, new nano- and hybrid- materials are introduced. Then, the developed working mechanisms, theoretical analysis, and computational simulation are presented. Next, based on different material design, diverse applications including human motion detection and health monitoring, soft robotics and human-machine interface, implantable devices, and biomedical applications are highlighted. Finally, synthesis consideration of the massive production industry of flexible strain sensors in the future; different fabrication approaches that are fully expected are classified and discussed.

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The development of wireless implantable sensors and integrated systems, enabled by advances in flexible and stretchable electronics technologies, is emerging to advance human health monitoring, diagnosis, and treatment. Progress in material and fabrication strategies allows for implantable electronics for unobtrusive monitoring via seamlessly interfacing with tissues and wirelessly communicating. Combining new nanomaterials and customizable printing processes offers unique possibilities for high-performance implantable electronics. Here, this report summarizes the recent progress and advances in nanomaterials and printing technologies to develop wireless implantable sensors and electronics. Advances in materials and printing processes are reviewed with a focus on challenges in implantable applications. Demonstrations of wireless implantable electronics and advantages based on these technologies are discussed. Lastly, existing challenges and future directions of nanomaterials and printing are described.

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Biosensors worn on or implanted in eyes have been garnering substantial attention since being proven to be an effective means to acquire critical biomarkers for monitoring the states of ophthalmic disease, diabetes. Among these disorders, glaucoma, the second leading cause of blindness globally, usually results in irreversible blindness. Continuous intraocular pressure (IOP) monitoring is considered as an effective measure, which provides a comprehensive view of IOP changes that is beyond reach for the "snapshots" measurements by clinical tonometry. However, to satisfy the applications in ophthalmology, the development of IOP sensors are required to be prepared with biocompatible, miniature, transparent, wireless and battery-free features, which are still challenging with many current fabrication processes. In this work, the recent advances in this field are reviewed by categorizing these devices into wearable and implantable IOP sensors. The materials and structures exploited for engineering these IOP devices are presented. Additionally, their working principle, performance, and the potential risk that materials and device architectures may pose to ocular tissue are discussed. This review should be valuable for preferable structure design, device fabrication, performance optimization, and reducing potential risk of these devices. It is significant for the development of future practical IOP sensors.

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Implantable sensors continuously transmit information on vital values or biomarker concentrations in bodily fluids, enabling physicians to survey disease progression and monitor therapeutic success. However, currently available technologies still face difficulties with long-term operation and transferability to different analytes. We show the potential of a generalizable platform based on gold nanoparticles embedded in a hydrogel for long-term implanted biosensing. Using optical imaging and an intelligent sensor/reference-design, we assess the tissue concentration of kanamycin in anesthetized rats by interrogating our implanted sensor noninvasively through the skin. Combining a tissue-integrating matrix, robust aptamer receptors, and photostable gold nanoparticles, our technology has strong potential to extend the lifetime of implanted sensors. Because of the easy adaptability of gold nanoparticles toward different analytes, our concept will find versatile applications in personalized medicine or pharmaceutical development.

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The ubiquity of vibration sensors and accelerometers, as well as advances in microfabrication technologies, have led to the development of implantable devices for biomedical applications. This work describes a piezoelectric microelectromechanical systems accelerometer designed for potential use in auditory prostheses. The design includes an aluminum nitride bimorph beam with a silicon proof mass. Analytic models of the device sensitivity and noise are presented. These lead to a minimum detectable acceleration cost function for the sensor that can be used to optimize sensor designs more effectively than typical sensitivity maximizing or electrical noise minimizing approaches. A fabricated device with a 1 µm thick, 100 µm long, and 700 µm wide beam and a 400 µm thick, 63 µm long, and 740 µm wide proof mass is tested experimentally. Results indicate accurate modeling of the system sensitivity up to the first resonant frequency (1420 Hz). The low-frequency sensitivity of the device is 1.3 mV/g, and the input referred noise is 36.3 nV / Hz at 100 Hz and 11.8 nV / Hz at 1 kHz. The resulting minimum detectable acceleration at 100 Hz and 1 kHz is 28 µg / Hz and 9.1 µg / Hz , respectively. A brief explanation of the use of the validated cost function for sensor design is provided, as well as an example comparing the piezoelectric sensor design to another from the literature. It is concluded that a traditional single-resonance design cannot compete with the performance of acoustic sensors; therefore, novel device designs must be considered for implantable auditory prosthesis applications.

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Fabrication of soft piezoelectric nanomaterials is essential for the development of wearable and implantable biomedical devices. However, a big challenge in this soft functional material development is to achieve a high piezoelectric property with long-term stability in a biological environment. Here, a one-step strategy for fabricating core/shell poly(vinylidene difluoride) (PVDF)/dopamine (DA) nanofibers (NFs) with a very high ß-phase content and self-aligned polarization is reported. The self-assembled core/shell structure is believed essential for the formation and alignment of ß-phase PVDF, where strong intermolecular interaction between the NH2 groups on DA and the CF2 groups on PVDF is responsible for aligning the PVDF chains and promoting ß-phase nucleation. The as-received PVDF/DA NFs exhibit significantly enhanced piezoelectric performance and excellent stability and biocompatibility. An all-fiber-based soft sensor is fabricated and tested on human skin and in vivo in mice. The devices show a high sensitivity and accuracy for detecting weak physiological mechanical stimulation from diaphragm motions and blood pulsation. This sensing capability offers great diagnostic potential for the early assessment and prevention of cardiovascular diseases and respiratory disorders.

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