Hydrogel-enabled skin bioelectronics that can continuously monitor health for extended periods is crucial for early disease detection and treatment. However, it is challenging to engineer ultrathin gas-permeable hydrogel sensors that can self-adhere to the human skin for long-term daily use (>1 week). Here, we present a ~10-micrometer-thick polyurethane nanomesh–reinforced gas-permeable hydrogel sensor that can self-adhere to the human skin for continuous and high-quality electrophysiological monitoring for 8 days under daily life conditions. This research involves two key steps: (i) material design by gelatin-based thermal-dependent phase change hydrogels and (ii) robust thinness geometry achieved through nanomesh reinforcement. The resulting ultrathin hydrogels exhibit a thickness of ~10 micrometers with superior mechanical robustness, high skin adhesion, gas permeability, and anti-drying performance. To highlight the potential applications in early disease detection and treatment that leverage the collective features, we demonstrate the use of ultrathin gas-permeable hydrogels for long-term, continuous high-precision electrophysiological monitoring under daily life conditions up to 8 days.

A 10-micrometer-thick nanomesh-reinforced gas-permeable hydrogel skin sensor for long-term electrophysiological monitoring

Electronic devices based on conducting polymer hydrogels have emerged as one of the most promising implantable bioelectronics for electrophysiological monitoring and diagnosis of a wide spectrum of diseases, in light of their distinct conductivity and biocompatibility. However, most conducting polymer hydrogels‐based bioelectronics are routinely fabricated through conventional techniques, which are challenged by its intrinsic poor processability of conducting polymers, as well as the essentially fragile biointerface, thus hampering their rapid innovation and application in advanced implantable bioelectronics. Here, 3D printable hydrogels based on poly(3,4‐ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) is reported, featuring superior 3D printability for direct ink writing (DIW), tissue‐like mechanical compliance (Young's modulus of 650 kPa), instant and tough bioadhesion (interfacial toughness of 200 J m−2 and shear strength of 120 kPa), highly‐tunable electrical properties, as well as long‐term in vitro and in vivo structural and electrochemical robustness. Electro‐physiological studies rat heart models with normal or arrhythmic conditions highlight the capabilities of establishing conformal biointerface with the dynamic organs, allowing for long‐term and high‐precision spatiotemporary epicardial electrophysiological monitoring, as well as electrical modulation of acute myocardial infarction (MI) model. These advances provide a promising strategy to improve the tissue‐electronics interfacing, and could serve as the basis for the next generation bioelectronics toward healthcare monitoring, diagnosis and medical therapies.

3D Printed Implantable Hydrogel Bioelectronics for Electrophysiological Monitoring and Electrical Modulation

Hydrogels and their sensors are emerging as key players in biomedical electronics, offering flexible, programmable structures and functions. Hydrogel-based sensors with stress–strain and electrophysiological sensing capabilities have consistently attracted interest. However, non-implantable hydrogel sensors often face challenges such as low sensitivity and slow response times, hindering their ability to detect subtle movements and causing delays in signal transmission. On the other hand, implantable hydrogel sensors, known for their biocompatibility and ionic conductivity, are better suited for long-term in vivo monitoring. Yet, their interface with biological tissues can lead to high impedance, adversely affecting signal quality and reducing sensor effectiveness. Furthermore, certain implantable hydrogel sensors may have limitations in light transmission properties, posing challenges in co-transmitting photoelectric signals for various applications. To address these challenges, researchers have been focusing on optimizing the mechanical and electrical properties of hydrogels. This involves modifications in precursor materials and structural designs, leading to the integration of multiple functionalities and significant performance improvements in hydrogel sensors. This systematic review covers existing studies on hydrogel sensors for biomedical electronics, from basic functionalities to more complex ones, and includes both non-implantable and implantable devices. Additionally, it provides insights into the future design principles and potential application scenarios for the next generation of multifunctional hydrogel sensors. 

Hydrogel sensors for biomedical electronics

Inkjet printing technology is a convenient, high-speed, and high-precision manufacturing tool, capable of achieving precise printing at both micro and nano scales. Composite hydrogel materials have garnered attention due to their excellent biocompatibility and outstanding mechanical properties. Combining inkjet printing technology with hydrogel materials for research and application holds the promise of significant breakthroughs in various fields, offering new development prospects for the construction of precise and complex biological tissues and biochips. In this review, we meticulously outline the research advancements in integrating inkjet printing technology with hydrogel materials. The high precision and accuracy of inkjet printing technology, with its inherent advantages, harmoniously complement the biocompatibility and mechanical properties of hydrogel materials. We delve deeply into the organic integration of these two in various fields, discussing the current state of research and the numerous challenges faced in their application studies. We specifically highlight the immense potential demonstrated in research areas such as particle loading and delivery, flexible circuits and sensors, bioengineering, and irregularly shaped hydrogels. Furthermore, we provide insights into the future development direction of the cohesive combination of inkjet printing technology and hydrogels. 

Research progress on the application of inkjet printing technology combined with hydrogels

Abstract Wearable skin-contacting devices are extensively studied for their ability to provide convenient and safe health monitoring. A key aspect that controls their performance are the properties of the device electrodes. Optimizing electrode structure, and the materials they are made from, can improve device functionality. Here, we discuss the various properties required for optimal electrode performance, including mechanical, electrical, and biocompatible factors. To address these challenges, we consider alteration of electrode structure, the development of flexible or soft conductive materials, and the creation of hybrid structures. Additionally, the integration of artificial intelligence is proposed as a promising direction to achieve smart devices. As well as outlining essential characteristics for high-performance wearable skin devices we also offer insight into possible future applications. 

Material and structural considerations for high-performance electrodes for wearable skin devices

Abstract Noninvasive brain–computer interfaces (BCIs) show great potential in applications including sleep monitoring, fatigue alerts, neurofeedback training, etc. While noninvasive BCIs do not impose any procedural risk to users (as opposed to invasive BCIs), the acquisition of high-quality electroencephalograms (EEGs) in the long term has been challenging due to the limitations of current electrodes. Herein, we developed a semidry double-layer hydrogel electrode that not only records EEG signals at a resolution comparable to that of wet electrodes but is also able to withstand up to 12 h of continuous EEG acquisition. The electrode comprises dual hydrogel layers: a conductive layer that features high conductivity, low skin-contact impedance, and high robustness; and an adhesive layer that can bond to glass or plastic substrates to reduce motion artifacts in wearing conditions. Water retention in the hydrogel is stable, and the measured skin-contact impedance of the hydrogel electrode is comparable to that of wet electrodes (conductive paste) and drastically lower than that of dry electrodes (metal pin). Cytotoxicity and skin irritation tests show that the hydrogel electrode has excellent biocompatibility. Finally, the developed hydrogel electrode was evaluated in both N170 and P300 event-related potential (ERP) tests on human volunteers. The hydrogel electrode captured the expected ERP waveforms in both the N170 and P300 tests, showing similarities in the waveforms generated by wet electrodes. In contrast, dry electrodes fail to detect the triggered potential due to low signal quality. In addition, our hydrogel electrode can acquire EEG for up to 12 h and is ready for recycled use (7-day tests). Altogether, the results suggest that our semidry double-layer hydrogel electrodes are able to detect ERPs in the long term in an easy-to-use fashion, potentially opening up numerous applications in real-life scenarios for noninvasive BCI. 

/pdf/hydrogel-electrodes-with-conductive-and-substrate-adhesive-2e1bpk4n.pdf

Hydrogel electrodes with conductive and substrate-adhesive layers for noninvasive long-term EEG acquisition

Neural stem cells (NSCs) are believed to have the most therapeutic potential for neurological disorders because they can differentiate into various neurons and glial cells. This research evaluated the safety and efficacy of intranasal administration of NSCs in children with cerebral palsy (CP). The functional brain network (FBN) analysis based on electroencephalogram (EEG) and voxel-based morphometry (VBM) analysis based on T1-weighted images were performed to evaluate functional and structural changes in the brain.A total of 25 CP patients aged 3-12 years were randomly assigned to the treatment group (n = 15), which received an intranasal infusion of NSCs loaded with nasal patches and rehabilitation therapy, or the control group (n = 10) received rehabilitation therapy only. The primary endpoints were the safety (assessed by the incidence of adverse events (AEs), laboratory and imaging examinations) and the changes in the Gross Motor Function Measure-88 (GMFM-88), the Activities of Daily Living (ADL) scale, the Sleep Disturbance Scale for Children (SDSC), and some adapted scales. The secondary endpoints were the FBN and VBM analysis.There were only four AEs happened during the 24-month follow-up period. There was no significant difference in the laboratory examinations before and after treatment, and the magnetic resonance imaging showed no abnormal nasal and intracranial masses. Compared to the control group, patients in the treatment group showed apparent improvements in GMFM-88 and ADL 24 months after treatment. Compared with the baseline, the scale scores of the Fine Motor Function, Sociability, Life Adaptability, Expressive Ability, GMFM-88, and ADL increased significantly in the treatment group 24 months after treatment, while the SDSC score decreased considerably. Compared with baseline, the FBN analysis showed a substantial decrease in brain network energy, and the VBM analysis showed a significant increase in gray matter volume in the treatment group after NSCs treatment.Our results showed that intranasal administration of NSCs was well-tolerated and potentially beneficial in children with CP.The study was registered in ClinicalTrials.gov (NCT03005249, registered 29 December 2016, https://www.gov/ct2/show/NCT03005249 ) and the Medical Research Registration Information System (CMR-20161129-1003). 

/pdf/safety-and-efficacy-outcomes-after-intranasal-administration-44vdxpmz.pdf

Safety and efficacy outcomes after intranasal administration of neural stem cells in cerebral palsy: a randomized phase 1/2 controlled trial

OBJECTIVE
Previous studies have revealed that, compared with Parkinson's disease (PD) patients without freezing of gait (FoG), the ones with FoG showed greater prefrontal activation while doing lower-limb movements involving standing, walking and turning, which require both locomotor and balance control. However, the relation between FoG and pure locomotor control as well as its underlying mechanism remain unclear.


METHODS
A total of 56 PD subjects were recruited and allocated to PD-FoG and PD-noFoG subgroups, and 34 age-matched heathy adults were included as heathy control (HC). Functional near-infrared spectroscopy was used to measure their prefrontal activation in a sitting lower-limb movement task, wherein subjects were asked to sit and tap their right toes as big and as fast as possible.


RESULTS
Result of one-way ANOVA (Group: PD-FoG vs. PD-noFoG vs. HC) revealed greater activation in the right prefrontal cortex in the PD-FoG group than in the other 2 groups. Linear mixed-effects model showed consistent result. Furthermore, the right prefrontal activation positively correlated with the severity of FoG symptoms in PD-FoG patients.


CONCLUSION
These findings suggested that PD patients with FoG require additional cognitive resources to compensate their damaged automaticity in locomotor control, which is more pronounced in severe FoG patients than milder ones.

Greater prefrontal activation during sitting toe tapping predicts severer freezing of gait in Parkinson's disease: an fNIRS study.

Quantitative evaluation of short-term resting-state brain networks for primary insomnia diagnosis

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Hydrogel electrodes with conductive and substrate-adhesive layers for noninvasive long-term EEG acquisition

Safety and efficacy outcomes after intranasal administration of neural stem cells in cerebral palsy: a randomized phase 1/2 controlled trial

Greater prefrontal activation during sitting toe tapping predicts severer freezing of gait in Parkinson's disease: an fNIRS study.

Quantitative evaluation of short-term resting-state brain networks for primary insomnia diagnosis