A skin-interfaced microfluidic platform supports dynamic sweat biochemical analysis during human exercise.

Blood lactate concentration is an established circulating biomarker for measuring muscle acidity and can be evaluated for monitoring endurance, training routines, or athletic performance. Sweat is an alternative biofluid that may serve similar purposes and offers the advantage of noninvasive collection and continuous monitoring. The relationship between blood lactate and dynamic sweat biochemistry for wearable engineering applications in physiological fitness remains poorly defined. Here, we developed a microfluidic wearable band with an integrated colorimetric timer and biochemical assays that temporally captures sweat and measures pH and lactate concentration. A colorimetric silver nanoplasmonic assay was used to measure the concentration of lactate, and dye-conjugated SiO2 nanoparticle-agarose composite materials supported dynamic pH analysis. We evaluated these sweat biomarkers in relation to blood lactate in human participant studies during cycling exercise of varying intensity. Iontophoresis-generated sweat pH from regions of actively working muscles decreased with increasing heart rate during exercise and was negatively correlated with blood lactate concentration. In contrast, sweat pH from nonworking muscles did not correlate with blood lactate concentration. Changes in sweat pH and blood lactate were observed in participants who did not regularly exercise but not in individuals who regularly exercised, suggesting a relationship to physical fitness and supporting further development for noninvasive, biochemical fitness evaluations.

Differences in the incidence, characteristics, and outcomes of patients with acute kidney injury in the medical and surgical intensive care units.

BACKGROUND: Though acute kidney injury (AKI) is a prevalent complication in critically ill patients, knowledge on the epidemiological differences and clinical characteristics of patients with AKI admitted to medical and surgical intensive care units (ICUs) remains limited. METHODS: Electronic medical records of patients in ICUs in Pusan National University Hospital and Pusan National University Hospital Yangsan, from January 2011 to December 2020, were retrospectively analyzed. Different characteristics of AKI between patients were analyzed. The contribution of AKI to the in-hospital mortality rate was assessed using a Cox proportional hazards model. RESULTS: A total of 7,150 patients were included in this study. AKI was more frequent in medical (48.7%) than in surgical patients (19.7%), with the severity of AKI higher in medical patients. In surgical patients, hospital-acquired AKI was more frequent (51.0% vs. 49.0%), whereas community-acquired AKI was more common in medical patients (58.5% vs. 41.5%). 16.9% and 5.9% of medical and surgical patients died in the hospital, respectively. AKI affected patient groups to different degrees. In surgical patients, AKI patients had 4.778 folds higher risk of mortality (95% confidence interval [CI], 3.577-6.382; p < 0.001) than non-AKI patients; whereas in medical AKI patients, it was 1.239 (95% CI, 1.051-1.461; p = 0.01). CONCLUSION: While the prevalence of AKI itself is higher in medical patients, the impact of AKI on mortality was stronger in surgical patients compared to medical patients. This suggests that more attention is needed for perioperative patients to prevent and manage AKI.

The role of nafamostat mesylate anticoagulation in continuous kidney replacement therapy for critically ill patients with bleeding tendencies: a retrospective study on patient outcomes and safety.

BACKGROUND: Continuous kidney replacement therapy (CKRT) is crucial in the management of acute kidney injury in intensive care units (ICUs). Nonetheless, the optimal anticoagulation strategy for patients with bleeding tendencies remains debated. This study aimed to evaluate patient outcomes and safety of nafamostat mesylate (NM) compared with no anticoagulation (NA) in critically ill patients with bleeding tendencies who were undergoing CKRT. METHODS: This retrospective study enrolled 2,313 patients who underwent CKRT between March 2013 and December 2022 at the third affiliated hospital in South Korea. After applying the exclusion criteria, 490 patients were included in the final analysis, with 245 patients in the NM and NA groups each, following 1:1 propensity score matching. Subsequently, in-hospital mortality, incidence of bleeding complications, agranulocytosis, hyperkalemia, and length of hospital stay were assessed. RESULTS: No significant differences were observed between the groups regarding the lengths of hospital and ICU stays or the incidence of agranulocytosis and hyperkalemia. The NM group showed a smaller decrease in hemoglobin levels during CKRT (-1.90 g/dL vs. -2.39 g/dL) and less need for blood product transfusions than the NA group. Furthermore, the NM group exhibited a survival benefit in patients who required transfusion of all three blood products. CONCLUSION: NM is an effective and safe anticoagulant for CKRT in critically ill patients, especially those requiring transfusion of all three blood products. Although these findings are promising, further multicenter studies are needed to validate them and explore the mechanisms underlying the observed benefits.

Degassing 4-tert-Butylpyridine in the Spiro-MeOTAD Film Improves the Thermal Stability of Perovskite Solar Cells.

The organic molecular 2,2',7,7'-tetrakis(4,4'-dimethoxy-3-methyldiphenylamino)-9,9'-spirobifluorene (Spiro-MeOTAD) is known as a typical hole transport material in the development of an all-solid-state perovskite solar cell (PSC). Spiro-MeOTAD requires additives of lithium bifurflimide (LiTFSI) and 4-tert-butylpyridine (tBP) to increase the conductivity and solubility for enhancing the photovoltaic performance of PSCs. However, those additives have an adverse effect on the thermal stability. We report on the origin of instability of additive-containing Spiro-MeOTAD at 85 °C and the methodology to solve the thermal instability. We have found that the interaction of LiTFSI with the underneath perovskite surface facilitated by diffusive tBP is responsible for thermal degradation. Degasification of tBP from the Spiro-MeOTAD film is found to be the key to achieving thermally stable PSCs, where the optimal degassing process achieves 90% of the initial power conversion efficiency (PCE) at 85 °C after 1000 h.

From lab to wearables: Innovations in multifunctional hydrogel chemistry for next-generation bioelectronic devices.

Functional hydrogels have emerged as foundational materials in diagnostics, therapy, and wearable devices, owing to their high stretchability, flexibility, sensing, and outstanding biocompatibility. Their significance stems from their resemblance to biological tissue and their exceptional versatility in electrical, mechanical, and biofunctional engineering, positioning themselves as a bridge between living organisms and electronic systems, paving the way for the development of highly compatible, efficient, and stable interfaces. These multifaceted capability revolutionizes the essence of hydrogel-based wearable devices, distinguishing them from conventional biomedical devices in real-world practical applications. In this comprehensive review, we first discuss the fundamental chemistry of hydrogels, elucidating their distinct properties and functionalities. Subsequently, we examine the applications of these bioelectronics within the human body, unveiling their transformative potential in diagnostics, therapy, and human-machine interfaces (HMI) in real wearable bioelectronics. This exploration serves as a scientific compass for researchers navigating the interdisciplinary landscape of chemistry, materials science, and bioelectronics.

Strain-invariant stretchable radio-frequency electronics.

Wireless modules that provide telecommunications and power-harvesting capabilities enabled by radio-frequency (RF) electronics are vital components of skin-interfaced stretchable electronics1-7. However, recent studies on stretchable RF components have demonstrated that substantial changes in electrical properties, such as a shift in the antenna resonance frequency, occur even under relatively low elastic strains8-15. Such changes lead directly to greatly reduced wireless signal strength or power-transfer efficiency in stretchable systems, particularly in physically dynamic environments such as the surface of the skin. Here we present strain-invariant stretchable RF electronics capable of completely maintaining the original RF properties under various elastic strains using a 'dielectro-elastic' material as the substrate. Dielectro-elastic materials have physically tunable dielectric properties that effectively avert frequency shifts arising in interfacing RF electronics. Compared with conventional stretchable substrate materials, our material has superior electrical, mechanical and thermal properties that are suitable for high-performance stretchable RF electronics. In this paper, we describe the materials, fabrication and design strategies that serve as the foundation for enabling the strain-invariant behaviour of key RF components based on experimental and computational studies. Finally, we present a set of skin-interfaced wireless healthcare monitors based on strain-invariant stretchable RF electronics with a wireless operational distance of up to 30 m under strain.

Materials and Structural Designs toward Motion Artifact-Free Bioelectronics.

Bioelectronics encompassing electronic components and circuits for accessing human information play a vital role in real-time and continuous monitoring of biophysiological signals of electrophysiology, mechanical physiology, and electrochemical physiology. However, mechanical noise, particularly motion artifacts, poses a significant challenge in accurately detecting and analyzing target signals. While software-based "postprocessing" methods and signal filtering techniques have been widely employed, challenges such as signal distortion, major requirement of accurate models for classification, power consumption, and data delay inevitably persist. This review presents an overview of noise reduction strategies in bioelectronics, focusing on reducing motion artifacts and improving the signal-to-noise ratio through hardware-based approaches such as "preprocessing". One of the main stress-avoiding strategies is reducing elastic mechanical energies applied to bioelectronics to prevent stress-induced motion artifacts. Various approaches including strain-compliance, strain-resistance, and stress-damping techniques using unique materials and structures have been explored. Future research should optimize materials and structure designs, establish stable processes and measurement methods, and develop techniques for selectively separating and processing overlapping noises. Ultimately, these advancements will contribute to the development of more reliable and effective bioelectronics for healthcare monitoring and diagnostics.

Polymeric Conductive Adhesive-Based Ultrathin Epidermal Electrodes for Long-Term Monitoring of Electrophysiological Signals.

Electrophysiology, exploring vital electrical phenomena in living organisms, anticipates broader integration into daily life through wearable devices and epidermal electrodes. However, addressing the challenges of the electrode durability and motion artifacts is essential to enable continuous and long-term biopotential signal monitoring, presenting a hurdle for its seamless implementation in daily life. To address these challenges, an ultrathin polymeric conductive adhesive, poly(3,4-ethylenedioxythiophene): poly(styrenesulfonate)/polyvinyl alcohol/d-sorbitol (PPd) electrode with enhanced adhesion, stretchability, and skin conformability, is presented. The skin conformability and stability of electrodes is designed by theoretical criteria obtained by mechanical analysis. Thus, impedance stability is obtained over 1-week of daily life, and the PPd electrode addresses the challenges related to durability during prolonged usage. Proving stability in electromyography (EMG) signals during high-intensity exercise, the wireless PPd measurement system exhibits high signal-to-noise ratio (SNR) signals even in situations involving significant and repetitive skin deformation. Throughout continuous 1 week-long electrocardiogram (ECG) monitoring in daily life, the system consistently preserves signal quality, underscoring the heightened durability and applicability of the PPd measurement system.

A Guide to Printed Stretchable Conductors.

Printing of stretchable conductors enables the fabrication and rapid prototyping of stretchable electronic devices. For such applications, there are often specific process and material requirements such as print resolution, maximum strain, and electrical/ionic conductivity. This review highlights common printing methods and compatible inks that produce stretchable conductors. The review compares the capabilities, benefits, and limitations of each approach to help guide the selection of a suitable process and ink for an intended application. We also discuss methods to design and fabricate ink composites with the desired material properties (e.g., electrical conductance, viscosity, printability). This guide should help inform ongoing and future efforts to create soft, stretchable electronic devices for wearables, soft robots, e-skins, and sensors.

Bionic artificial skin with a fully implantable wireless tactile sensory system for wound healing and restoring skin tactile function.

Tactile function is essential for human life as it enables us to recognize texture and respond to external stimuli, including potential threats with sharp objects that may result in punctures or lacerations. Severe skin damage caused by severe burns, skin cancer, chemical accidents, and industrial accidents damage the structure of the skin tissue as well as the nerve system, resulting in permanent tactile sensory dysfunction, which significantly impacts an individual's daily life. Here, we introduce a fully-implantable wireless powered tactile sensory system embedded artificial skin (WTSA), with stable operation, to restore permanently damaged tactile function and promote wound healing for regenerating severely damaged skin. The fabricated WTSA facilitates (i) replacement of severely damaged tactile sensory with broad biocompatibility, (ii) promoting of skin wound healing and regeneration through collagen and fibrin-based artificial skin (CFAS), and (iii) minimization of foreign body reaction via hydrogel coating on neural interface electrodes. Furthermore, the WTSA shows a stable operation as a sensory system as evidenced by the quantitative analysis of leg movement angle and electromyogram (EMG) signals in response to varying intensities of applied pressures.

Wearable and Implantable Cortisol-Sensing Electronics for Stress Monitoring.

Cortisol is a steroid hormone that is released from the body in response to stress. Although a moderate level of cortisol secretion can help the body maintain homeostasis, excessive secretion can cause various diseases, such as depression and anxiety. Conventional methods for cortisol measurement undergo procedures that limit continuous monitoring, typically collecting samples of bodily fluids, followed by separate analysis in a laboratory setting that takes several hours. Thus, recent studies demonstrate wearable, miniaturized sensors integrated with electronic modules that enable wireless real-time analysis. Here, the primary focus is on wearable and implantable electronic devices that continuously measure cortisol concentration. Diverse types of cortisol-sensing techniques, such as antibody-, DNA-aptamer-, and molecularly imprinted polymer-based sensors, as well as wearable and implantable devices that aim to continuously monitor cortisol in a minimally invasive fashion are discussed. In addition to the cortisol monitors that directly measure stress levels, other schemes that indirectly measure stress, such as electrophysiological signals and sweat are also summarized. Finally, the challenges and future directions in stress monitoring and management electronics are reviewed.

Clinical evaluation of 3.0-mm narrow-diameter implants: a retrospective study with up to 5 years of observation.

PURPOSE: This study aimed to evaluate the clinical outcomes of a single type of narrow-diameter implant (NDI) by investigating its survival rate and peri-implant marginal bone loss (MBL). In addition, variables possibly related to implant survival and MBL were investigated to identify potential risk factors. METHODS: The study was conducted as a retrospective study involving 49 patients who had received 3.0-mm diameter TSIII implants (Osstem Implant Co.) at Seoul National University Dental Hospital. In total, 64 implants were included, and dental records and radiographic data were collected from 2017 to 2022. Kaplan-Meier survival curves and a Cox proportional hazard model were used to estimate the implant survival rate and to investigate the effects of age, sex, jaw, implant location, implant length, the stage of surgery, guided bone regeneration, type of implant placement, and the surgeon's proficiency (resident or professor) on implant survival. The MBL of the NDIs was measured, and the factors influencing MBL were evaluated. RESULTS: The mean observation period was 30.5 months (interquartile range, 26.75-45 months), and 6 out of 64 implants failed. The survival rate of the NDIs was 90.6%, and the multivariate Cox regression analysis showed that age was associated with implant failure (hazard ratio, 1.17; 95% confidence interval, 1.04-1.31, P=0.01). The mean MBL was 0.44±0.75 mm, and no factors showed statistically significant associations with greater MBL. CONCLUSIONS: NDIs can be considered a primary alternative when standard-diameter implants are unsuitable. However, further studies are required to confirm their long-term stability.

Micro-syringe chip-guided intratumoral administration of lipid nanoparticles for targeted anticancer therapy.

BACKGROUND: Nano-sized drug delivery system has been widely studied as a potential technique to promote tumor-specific delivery of anticancer drugs due to its passive targeting property, but resulting in very restricted improvements in its systemic administration so far. There is a requirement for a different approach that dramatically increases the targeting efficiency of therapeutic agents at targeted tumor tissues. METHODS: To improve the tumor-specific accumulation of anticancer drugs and minimize their undesirable toxicity to normal tissues, a tumor-implantable micro-syringe chip (MSC) with a drug reservoir is fabricated. As a clinically established delivery system, six liposome nanoparticles (LNPs) with different compositions and surface chemistry are prepared and their physicochemical properties and cellular uptake are examined in vitro. Subsequently, MSC-guided intratumoral administration is studied to identify the most appropriate for the higher tumor targeting efficacy with a uniform intratumoral distribution. For efficient cancer treatment, pro-apoptotic anticancer prodrugs (SMAC-P-FRRG-DOX) are encapsulated to the optimal LNPs (SMAC-P-FRRG-DOX encapsulating LNPs; ApoLNPs), then the ApoLNPs are loaded into the 1 µL-volume drug reservoir of MSC to be delivered intratumorally for 9 h. The tumor accumulation and therapeutic effect of ApoLNPs administered via MSC guidance are evaluated and compared to those of intravenous and intratumoral administration of ApoLNP in 4T1 tumor-bearing mice. RESULTS: MSC is precisely fabricated to have a 0.5 × 4.5 mm needle and 1 µL-volume drug reservoir to achieve the uniform intratumoral distribution of LNPs in targeted tumor tissues. Six liposome nanoparticles with different compositions of 1-palmitoyl-2-oleoyl-glycero-3-phosphocholine (PC), 1,2-dioleoyl-sn-glycero-3-phospho-L-serine (PS), 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy (polyethylene glycol)2000] (PEG2000-DSPE) are prepared with average sizes of 100-120 nm and loaded into the 1 µL-volume drug reservoir in MSC. Importantly negatively charged 10 mol% of PS-containing LNPs are very slowly infused into the tumor tissue through the micro-syringe of the MSC over 6 h. The intratumoral targeting efficiency of MSC guidance is 93.5%, effectively assisting the homogeneous diffusion of LNPs throughout the tumor tissue at 3.8- and 2.7-fold higher concentrations compared to the intravenous and intratumoral administrations of LNPs, respectively. Among the six LNP candidates 10 mol% of PS-containing LNPs are finally selected for preparing pro-apoptotic SMAC-P-FRRG-DOX anticancer prodrug-encapsulated LNPs (ApoLNPs) due to their moderate endocytosis rate high tumor accumulation and homogenous intratumoral distribution. The ApoLNPs show a high therapeutic effect specifically to cathepsin B-overexpressing cancer cells with 6.6 µM of IC50 value while its IC50 against normal cells is 230.7 µM. The MSC-guided administration of ApoLNPs efficiently inhibits tumor growth wherein the size of the tumor is 4.7- and 2.2-fold smaller than those treated with saline and intratumoral ApoLNP without MSC, respectively. Moreover, the ApoLNPs remarkably reduce the inhibitor of apoptosis proteins (IAPs) level in tumor tissues confirming their efficacy even in cancers with high drug resistance. CONCLUSION: The MSC-guided administration of LNPs greatly enhances the therapeutic efficiency of anticancer drugs via the slow diffusion mechanism through micro-syringe to tumor tissues for 6 h, whereas they bypass most hurdles of systemic delivery including hepatic metabolism, rapid renal clearance, and interaction with blood components or other normal tissues, resulting in the minimum toxicity to normal tissues. The negatively charged ApoLNPs with cancer cell-specific pro-apoptotic prodrug (SMAC-P-FRRG-DOX) show the highest tumor-targeting efficacy when they are treated with the MSC guidance, compared to their intravenous or intratumoral administration in 4T1 tumor-bearing mice. The MSC-guided administration of anticancer drug-encapsulated LNPs is expected to be a potent platform system that facilitates overcoming the limitations of systemic drug administration with low delivery efficiency and serious side effects.

Bidirectional associations between periodontal disease and systemic diseases: a nationwide population-based study in Korea.

To evaluate the associations of periodontal disease (PD) with systemic diseases, including diabetes mellitus (DM) and cardiovascular disease (CVD), as well as the reciprocal association. The CVD included the cases of coronary heart disease and heart failure. A prospective study was conducted from 2007 to 2019 using linked data from three databases in Korea. Three separate study groups were formed to individually determine the risks of PD (n = 10,533), DM (n = 14,523) and CVD (n = 14,315). All diseases were confirmed based on physicians' diagnoses using medical records and self-reports. Cox proportional hazard regression was applied with 95% confidence intervals (CIs) to obtain hazard ratios (HRs). PD was significantly associated with an elevated risk of DM (HR [95% CI]: 1.22 [1.07-1.39]) after full adjustment for age, sex, lifestyle factors, body mass index, dental behaviour and CVD. PD was also found to increase the risk of CVD (1.27 [1.03-1.57]), whereas CVD increased the risk of PD (1.20 [1.09-1.32]) after full adjustment for other covariates including DM. This study found a bidirectional association between PD and CVD, as well as a positive association of PD with DM.

SinusC-Net for automatic classification of surgical plans for maxillary sinus augmentation using a 3D distance-guided network.

The objective of this study was to automatically classify surgical plans for maxillary sinus floor augmentation in implant placement at the maxillary posterior edentulous region using a 3D distance-guided network on CBCT images. We applied a modified ABC classification method consisting of five surgical approaches for the deep learning model. The proposed deep learning model (SinusC-Net) consisted of two stages of detection and classification according to the modified classification method. In detection, five landmarks on CBCT images were automatically detected using a volumetric regression network; in classification, the CBCT images were automatically classified as to the five surgical approaches using a 3D distance-guided network. The mean MRE for landmark detection was 0.87 mm, and SDR for 2 mm or lower, 95.47%. The mean accuracy, sensitivity, specificity, and AUC for classification by the SinusC-Net were 0.97, 0.92, 0.98, and 0.95, respectively. The deep learning model using 3D distance-guidance demonstrated accurate detection of 3D anatomical landmarks, and automatic and accurate classification of surgical approaches for sinus floor augmentation in implant placement at the maxillary posterior edentulous region.

Thermally Managed, Injectable Optoelectronic Probe with Heat Dissipation Guide for Photodynamic Therapy.

The development of fabrication technologies and appearance of new materials has resulted in dramatic increase in the performance of electronic devices, while the overall size has decreased. Recent electronic devices made of micro/nano-size components show high efficiency and outstanding performance with compact size, but these devices have revealed several fatal problems. In particular, the isolated heat that is generated by numerous components concentrated in a limited small area at high density, such as bio-integrated devices, is an issue that needs to be urgently addressed, because it is closely related to the performance and lifetime of electronic devices. To solve these problems, the microscale light emitting diode (µLED)-based neural probe is introduced on an injectable heat dissipation guide. The heat dissipation guide is made of boron nitride (BN) nanomaterials with high thermal conductivity. The heat management noticeably improves the optical output performance of the µLEDs, in which BN effectively dissipates heat, and allows enhanced lighting from the LEDs to be transmitted through brain tissue without thermal damage. Moreover, it shows remarkable improvement in the therapeutic effect of photodynamic therapy of mouse cancer cells.

A wireless and battery-less implant for multimodal closed-loop neuromodulation in small animals.

Fully implantable wireless systems for the recording and modulation of neural circuits that do not require physical tethers or batteries allow for studies that demand the use of unconstrained and freely behaving animals in isolation or in social groups. Moreover, feedback-control algorithms that can be executed within such devices without the need for remote computing eliminate virtual tethers and any associated latencies. Here we report a wireless and battery-less technology of this type, implanted subdermally along the back of freely moving small animals, for the autonomous recording of electroencephalograms, electromyograms and body temperature, and for closed-loop neuromodulation via optogenetics and pharmacology. The device incorporates a system-on-a-chip with Bluetooth Low Energy for data transmission and a compressed deep-learning module for autonomous operation, that offers neurorecording capabilities matching those of gold-standard wired systems. We also show the use of the implant in studies of sleep-wake regulation and for the programmable closed-loop pharmacological suppression of epileptic seizures via feedback from electroencephalography. The technology can support a broader range of applications in neuroscience and in biomedical research with small animals.

A battery-less wireless implant for the continuous monitoring of vascular pressure, flow rate and temperature.

Devices for monitoring blood haemodynamics can guide the perioperative management of patients with cardiovascular disease. Current technologies for this purpose are constrained by wired connections to external electronics, and wireless alternatives are restricted to monitoring of either blood pressure or blood flow. Here we report the design aspects and performance parameters of an integrated wireless sensor capable of implantation in the heart or in a blood vessel for simultaneous measurements of pressure, flow rate and temperature in real time. The sensor is controlled via long-range communication through a subcutaneously implanted and wirelessly powered Bluetooth Low Energy system-on-a-chip. The device can be delivered via a minimally invasive transcatheter procedure or it can be mounted on a passive medical device such as a stent, as we show for the case of the pulmonary artery in a pig model and the aorta and left ventricle in a sheep model, where the device performs comparably to clinical tools for monitoring of blood flow and pressure. Battery-less and wireless devices such as these that integrate capabilities for flow, pressure and temperature sensing offer the potential for continuous monitoring of blood haemodynamics in patients.

Optical neuromodulation at all scales: from nanomaterials to wireless optoelectronics and integrated systems.

Light-based neuromodulation systems offer exceptional spatiotemporal resolution combined with the elimination of physical tether to communicate with neurons. Currently, optical neuromodulation systems ranging from the nano to the centimeter scale enable neural activity control from the single cell to the organ level in retina, heart, spinal cord, and brain, facilitating a wide range of experiments in intact and freely moving animals in different contexts, such as during social interactions and behavioral tasks. Nanotransducers (e.g., metallic nanoparticles, silicon nanowires, and polymeric nanoparticles) and microfabricated photodiodes convert light to electrical, thermal, and mechanical stimuli that can allow remote and non-contact stimulation of neurons. Moreover, integrated devices composed of nano and microscale optoelectronic components comprise fully implantable and wirelessly powered smart optoelectronic systems that exhibit multimodal and closed-loop operation. In this review, we first discuss the material platforms, stimulation mechanisms, and applications of passive systems, i.e., nanotransducers and microphotodiodes. Then, we review the use of organic and inorganic light-emitting diodes for optogenetics and implantable wireless optoelectronic systems that enable closed-loop optogenetic neuromodulation through the use of light-emitting diodes, wireless power transfer circuits, and feedback loops. Exploration of materials and mechanisms together with the presented applications from both research and clinical perspectives in this review provides a comprehensive understanding of the optical neuromodulation field with its advantages and challenges to build superior systems in the future.

Polyethylenimine-Conjugated Hydroxyethyl Cellulose for Doxorubicin/Bcl-2 siRNA Co-Delivery Systems.

Hydroxyethyl cellulose (HEC), widely known for its biocompatibility and water solubility, is a polysaccharide with potential for pharmaceutical applications. Here, we synthesized polyethylenimine2k (PEI2k)-conjugated hydroxyethyl cellulose (HECP2k) for doxorubicin/Bcl-2 siRNA co-delivery systems. HECP2ks were synthesized by reductive amination of PEI2k with periodate-oxidized HEC. The synthesis of the polymers was characterized using 1H NMR, 13C NMR, primary amine quantification, FT-IR, and GPC. Via agarose gel electrophoresis and Zeta-sizer measurement, it was found that HECP2ks condensed pDNA to positively charged and nano-sized complexes (100-300 nm, ~30 mV). The cytotoxicity of HECP2ks was low and HECP2k 10X exhibited higher transfection efficiency than PEI25k even in serum condition, showing its high serum stability from ethylene oxide side chains. Flow cytometry analysis and confocal laser microscopy observation verified the superior cellular uptake and efficient endosome escape of HECP2k 10X. HECP2k 10X also could load Dox and Bcl-2 siRNA, forming nano-particles (HECP2k 10X@Dox/siRNA). By median effect analysis and annexin V staining analysis, it was found that HECP2k 10X@Dox/siRNA complexes could cause synergistically enhanced anti-cancer effects to cancer cells via induction of apoptosis. Consequently, it was concluded that HECP2k possesses great potential as a promising Dox/Bcl-2 siRNA co-delivery carrier.