Stretchable Functional Nanocomposites for Soft Implantable Bioelectronics.

Material advances in soft bioelectronics, particularly those based on stretchable nanocomposites─functional nanomaterials embedded in viscoelastic polymers with irreversible or reversible bonds─have driven significant progress in translational medical device research. The unique mechanical properties inherent in the stretchable nanocomposites enable stiffness matching between tissue and device, as well as its spontaneous mechanical adaptation to in vivo environments, minimizing undesired mechanical stress and inflammation responses. Furthermore, these properties allow percolative networks of conducting fillers in the nanocomposites to be sustained even under repetitive tensile/compressive stresses, leading to stable tissue-device interfacing. Here, we present an in-depth review of materials strategies, fabrication/integration techniques, device designs, applications, and translational opportunities of nanocomposite-based soft bioelectronics, which feature intrinsic stretchability, self-healability, tissue adhesion, and/or syringe injectability. Among many, applications to brain, heart, and peripheral nerves are predominantly discussed, and translational studies in certain domains such as neuromuscular and cardiovascular engineering are particularly highlighted.

A Dual-Mode CMOS Power Amplifier with an External Power Amplifier Driver Using 40 nm CMOS for Narrowband Internet-of-Things Applications.

The narrowband Internet-of-Things (NB-IoT) has been developed to provide low-power, wide-area IoT applications. The efficiency of a power amplifier (PA) in a transmitter is crucial for a longer battery lifetime, satisfying the requirements for output power and linearity. In addition, the design of an internal complementary metal-oxide semiconductor (CMOS) PA is typically required when considering commercial applications to include the operation of an optional external PA. This paper presents a dual-mode CMOS PA with an external PA driver for NB-IoT applications. The proposed PA supports an external PA mode without degrading the performances of output power, linearity, and stability. In the operation of an external PA mode, the PA provides a sufficient gain to drive an external PA. A parallel-combined transistor method is adopted for a dual-mode operation and a third-order intermodulation distortion (IMD3) cancellation. The proposed CMOS PA with an external PA driver was implemented using 40 nm-CMOS technology. The PA achieves a gain of 20.4 dB, a saturated output power of 28.8 dBm, and a power-added efficiency (PAE) of 57.8% in high-power (HP) mode at 920 MHz. With an NB-IoT signal (200 kHz π/4-differential quadrature phase shift keying (DQPSK)), the proposed PA achieves 24.2 dBm output power (Pout) with a 31.0% PAE, while satisfying -45 dBc adjacent channel leakage ratio (ACLR). More than 80% of the current consumption at 12 dBm Pout could be saved compared to that in HP mode when the proposed PA operates in low-power (LP) mode. The implemented dual-mode CMOS PA provides high linear output power with high efficiency, while supporting an external PA mode. The proposed PA is a good candidate for NB-IoT applications.

Sticky and Strain-Gradient Artificial Epineurium for Sutureless Nerve Repair in Rodents and Nonhuman Primates.

The need for the development of soft materials capable of stably adhering to nerve tissues without any suturing followed by additional damages is at the fore at a time when success in postoperative recovery depends largely on the surgical experience and/or specialized microsuturing skills of the surgeon. Despite fully recognizing such prerequisite conditions, designing the materials with robust adhesion to wet nerves as well as acute/chronic anti-inflammation remains to be resolved. Herein, a sticky and strain-gradient artificial epineurium (SSGAE) that overcomes the most critically challenging aspect for realizing sutureless repair of severely injured nerves is presented. In this regard, the SSGAE with a skin-inspired hierarchical structure entailing strain-gradient layers, anisotropic Janus layers including hydrophobic top and hydrophilic bottom surfaces, and synergistic self-healing capabilities enables immediate and stable neurorrhaphy in both rodent and nonhuman primate models, indicating that the bioinspired materials strategy significantly contributes to translational medicine for effective peripheral nerve repair.

Defect-Engineered Semiconducting van der Waals Thin Film at Metal-Semiconductor Interface of Field-Effect Transistors.

The significance of metal-semiconductor interfaces and their impact on electronic device performance have gained increasing attention, with a particular focus on investigating the contact metal. However, another avenue of exploration involves substituting the contact metal at the metal-semiconductor interface of field-effect transistors with semiconducting layers to introduce additional functionalities to the devices. Here, a scalable approach for fabricating metal-oxide-semiconductor (channel)-semiconductor (interfacial layer) field-effect transistors is proposed by utilizing solution-processed semiconductors, specifically semiconducting single-walled carbon nanotubes and molybdenum disulfide, as the channel and interfacial semiconducting layers, respectively. The work function of the interfacial MoS2 is modulated by controlling the sulfur vacancy concentration through chemical treatment, which results in distinctive energy band alignments within a single device configuration. The resulting band alignments lead to multiple functionalities, including multivalued transistor characteristics and multibit nonvolatile memory (NVM) behavior. Moreover, leveraging the stable NVM properties, we demonstrate artificial synaptic devices with 88.9% accuracy of MNIST image recognition.

Soft and Conductive Polyethylene Glycol Hydrogel Electrodes for Electrocardiogram Monitoring.

The measurement of biosignals in the clinical and healthcare fields is fundamental; however, conventional electrodes pose challenges such as incomplete skin contact and skin-related issues, hindering accurate biosignal measurement. To address these challenges, conductive hydrogels, which are valuable owing to their biocompatibility and flexibility, have been widely developed and explored for electrode applications. In this study, we fabricated a conductive hydrogel by mixing polyethylene glycol diacrylate (PEGDA) with poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) polymers dissolved in deionized water, followed by light-triggered crosslinking. Notably, this study pioneered the use of a PEGDA-PEDOT:PSS hydrogel for electrocardiogram (ECG) monitoring- a type of biosignal. The resulting PEGDA-PEDOT:PSS hydrogel demonstrated remarkable conductivity while closely approximating the modulus of skin elasticity. Additionally, it demonstrated biocompatibility and a high signal-to-noise ratio in the waveforms. This study confirmed the exceptional suitability of the PEGDA-PEDOT:PSS hydrogel for accurate biosignal measurements with potential applications in various wearable devices designed for biosignal monitoring.

Injectable tissue prosthesis for instantaneous closed-loop rehabilitation.

To construct tissue-like prosthetic materials, soft electroactive hydrogels are the best candidate owing to their physiological mechanical modulus, low electrical resistance and bidirectional stimulating and recording capability of electrophysiological signals from biological tissues1,2. Nevertheless, until now, bioelectronic devices for such prostheses have been patch type, which cannot be applied onto rough, narrow or deep tissue surfaces3-5. Here we present an injectable tissue prosthesis with instantaneous bidirectional electrical conduction in the neuromuscular system. The soft and injectable prosthesis is composed of a biocompatible hydrogel with unique phenylborate-mediated multiple crosslinking, such as irreversible yet freely rearrangeable biphenyl bonds and reversible coordinate bonds with conductive gold nanoparticles formed in situ by cross-coupling. Closed-loop robot-assisted rehabilitation by injecting this prosthetic material is successfully demonstrated in the early stage of severe muscle injury in rats, and accelerated tissue repair is achieved in the later stage.

Radiologic Progression of Interstitial Lung Abnormalities following Surgical Resection in Patients with Lung Cancer.

In this study, we aimed to assess the prevalence of interstitial lung abnormalities (ILAs) and investigate the rates and risk factors associated with radiologic ILA progression among patients with lung cancer following surgical resection. Patients who underwent surgical resection for lung cancer at our institution from January 2015 to December 2020 were retrospectively evaluated and grouped according to their ILA status as having no ILAs, equivocal ILAs, or ILAs. Progression was determined by simultaneously reviewing the baseline and corresponding follow-up computed tomography (CT) scans. Among 346 patients (median age: 67 (interquartile range: 60-74) years, 204 (59.0%) men), 22 (6.4%) had equivocal ILAs, and 33 (9.5%) had ILAs detected upon baseline CT. Notably, six patients (6/291; 2.1%) without ILAs upon baseline CT later developed ILAs, and 50% (11/22) of those with equivocal ILAs exhibited progression. Furthermore, 75.8% (25/33) of patients with ILAs upon baseline CT exhibited ILA progression (76.9% and 71.4% with fibrotic and non-fibrotic ILAs, respectively). Multivariate analysis revealed that ILA status was a significant risk factor for ILA progression. ILAs and equivocal ILAs were associated with radiologic ILA progression after surgical resection in patients with lung cancer. Hence, early ILA detection can significantly affect clinical outcomes.

Comparison of Prophylactic Effects between Localized Biomimetic Minocycline and Systematic Amoxicillin on Implants Placed Immediately in Infected Sockets.

This study evaluated the prophylactic effect of localized biomimetic minocycline and systemic amoxicillin on immediate implant placement at infected extraction sites. Twelve mongrels with six implants each were randomly assigned to five groups: uninfected negative control (Group N); infected with oral complex bacteria (Group P); infected and treated with amoxicillin one hour before implant placement (Group A); infected and treated with minocycline during implant placement (Group B); and infected and treated with amoxicillin one hour before implant placement and with minocycline during implant placement (Group C). Radiographic bone level, gingival index (GI), probing depth (PD), papillary bleeding index (PBI), and removal torque (RT) were recorded. There was no significant difference between Groups A, B, and C for bone loss. Group A showed the highest RT, the lowest PBI, and significantly lower GI and PD values than Group P. Group B exhibited significantly higher RT value than Group N and significantly smaller PD value than Group P at 6 w postoperatively. Localized minocycline could improve implant success by reducing bone loss and increasing RT and systemic amoxicillin could maintain the stability of the peri-implant soft tissue. However, combined use of these two antibiotics did not augment the prophylactic effect.

Wearable Liquid Metal Composite with Skin-Adhesive Chitosan-Alginate-Chitosan Hydrogel for Stable Electromyogram Signal Monitoring.

In wearable bioelectronics, various studies have focused on enhancing prosthetic control accuracy by improving the quality of physiological signals. The fabrication of conductive composites through the addition of metal fillers is one way to achieve stretchability, conductivity, and biocompatibility. However, it is difficult to measure stable biological signals using these soft electronics during physical activities because of the slipping issues of the devices, which results in the inaccurate placement of the device at the target part of the body. To address these limitations, it is necessary to reduce the stiffness of the conductive materials and enhance the adhesion between the device and the skin. In this study, we measured the electromyography (EMG) signals by applying a three-layered hydrogel structure composed of chitosan-alginate-chitosan (CAC) to a stretchable electrode fabricated using a composite of styrene-ethylene-butylene-styrene and eutectic gallium-indium. We observed stable adhesion of the CAC hydrogel to the skin, which aided in keeping the electrode attached to the skin during the subject movement. Finally, we fabricated a multichannel array of CAC-coated composite electrodes (CACCE) to demonstrate the accurate classification of the EMG signals based on hand movements and channel placement, which was followed by the movement of the robot arm.

Stretchable Gold Nanomembrane Electrode with Ionic Hydrogel Skin-Adhesive Properties.

Skin has a dynamic surface and offers essential information through biological signals originating from internal organs, blood vessels, and muscles. Soft and stretchable bioelectronics can be used in wearable machines for long-term stability and to continuously obtain distinct bio-signals in conjunction with repeated expansion and contraction with physical activities. While monitoring bio-signals, the electrode and skin must be firmly attached for high signal quality. Furthermore, the signal-to-noise ratio (SNR) should be high enough, and accordingly, the ionic conductivity of an adhesive hydrogel needs to be improved. Here, we used a chitosan-alginate-chitosan (CAC) triple hydrogel layer as an interface between the electrodes and the skin to enhance ionic conductivity and skin adhesiveness and to minimize the mechanical mismatch. For development, thermoplastic elastomer Styrene-Ethylene-Butylene-Styrene (SEBS) dissolved in toluene was used as a substrate, and gold nanomembranes were thermally evaporated on SEBS. Subsequently, CAC triple layers were drop-casted onto the gold surface one by one and dried successively. Lastly, to demonstrate the performance of our electrodes, a human electrocardiogram signal was monitored. The electrodes coupled with our CAC triple hydrogel layer showed high SNR with clear PQRST peaks.