Trigger-Detachable Hydrogel Adhesives for Bioelectronic Interfaces

Recent electronics technology development has provided unprecedented opportunities for enabling implantable bioelectronics for long-term disease monitoring and treatment. Current electronics-tissue interfaces are characterized by weak physical interactions, suffering from potential interfacial failure or dislocation during long-term application. On the other hand, some new technologies can be used to achieve robust electronics-tissue interfaces; however, such technologies are limited by potential risks and the discomfort associated with postdetachment of the bioelectronics. Here, a hydrogel-based electronics-tissue interface based on the exploitation of dynamic interactions (such as boronate-diol complexation) that features an interfacial toughness over 400 J m⁻² is presented. Moreover, these hydrogel adhesion layers are also trigger-detachable by dissociating the dynamic complexes (i.e., addition of glucose). These hydrogel-based bioelectronic interfaces enable the in vivo recording of physiological signals (i.e., electromyograph, blood pressure, or pulse rates). Upon mild triggering, these bioelectronics can be easily detached without causing any damage, trauma, or discomfort to the skin, tissues, and organs. This kind of trigger-detachable hydrogel adhesives offer general applicability in bioelectronic interfaces, exhibiting promising utility in monitoring, modulating, and treating diseases where temporary monitoring of physiologic signals, interfacial robustness, and postremoval of bioelectronics are required.     

Self‐Healing Silk Fibroin‐Based Hydrogel for Bone Regeneration: Dynamic Metal‐Ligand Self‐Assembly Approach

Despite advances in the development of silk fibroin (SF)‐based hydrogels, current methods for SF gelation show significant limitations such as lack of reversible crosslinking, use of nonphysiological conditions, and difficulties in controlling gelation time. In the present study, a strategy based on dynamic metal‐ligand coordination chemistry is developed to assemble SF‐based hydrogel under physiological conditions between SF microfibers (mSF) and a polysaccharide binder. The presented SF‐based hydrogel exhibits shear‐thinning and autonomous self‐healing properties, thereby enabling the filling of irregularly shaped tissue defects without gel fragmentation. A biomineralization approach is used to generate calcium phosphate‐coated mSF, which is chelated by bisphosphonate ligands of the binder to form reversible crosslinkages. Robust dually crosslinked (DC) hydrogel is obtained through photopolymerization of acrylamide groups of the binder. DC SF‐based hydrogel supports stem cell proliferation in vitro and accelerates bone regeneration in cranial critical size defects without any additional morphogenes delivered. The developed self‐healing and photopolymerizable SF‐based hydrogel possesses significant potential for bone regeneration application with the advantages of injectability and fit‐to‐shape molding.     

Hydration-Induced β-Sheet Crosslinking of α-Helical-Rich Spider Prey-Wrapping Silk

Due to its moderate strength (≈700 MPa) and impressive extensibility before breaking (≈60–80%), orb-weaving spider aciniform (AC) prey-wrapping silks are actually the toughest of the spider silks but are remarkably understudied. The previous results indicate that native AC silk fibers are an α-helix rich coiled-coil/β-sheet hybrid nanofiber, and that conversion of disordered or helical domains to β-sheet aggregates is surprisingly minimal and overall β-sheet content is low (≈15%). In this work, it is demonstrated through scanning electron microscopy that native AC silk fibers undergo matted cross-linking upon exposure to moisture that increases silk stiffness. The unique molecular mechanism of water-induced cross-linking is revealed with solid-state NMR (SSNMR) methods; water-induced morphological changes are correlated with an increase in AC silk protein β-sheet content, and additionally a minor unfolding of coiled-coil regions is observed. Continued and increased β-sheet cross-linking is observed upon application of mechanical shear. The size of these β-sheet domains to be 4–6 nm using Wide-Line Separation SSNMR is determined. The observation that merely water treatment can be used to convert a protein-based material from a flexible/extensible α-helix-rich fiber to a rigid crossed-linked β-sheet mat is a novel observation that should provide new avenues in bioinspired materials design.     

Intelligent Silk Fibroin Based Microneedle Dressing (i-SMD)

Wounds, especially those caused by chronic diseases, are severe threats to human health. To facilitate their recovery, considerable efforts have been devoted to the generation of wound tissues and the detection of wound biomarkers. Here, an intelligent origami silk fibroin microneedle-structured dressing (i-SMD) with a smart drug release system, biochemical sensing, and physiological monitoring ability for epidermal sensing and wound healing, is presented. By utilizing temperature-responsive N-isopropylacrylamide (NIPAM) hydrogel and inverse opal (IO) photonic crystals (PCs) as a smart drug release system, controllable drug release is achieved on the i-SMD. The patterned microfluidic channels on the i-SMD and IO PCs enable the liquid to flow spontaneously in the channels, thereby achieving sensitive multiple biochemical analysis of inflammatory factors; meanwhile, microelectronic circuits integrated on the i-SMD enable sensitive motion monitoring. Notably, the performance of i-SMD in facilitating wound healing is demonstrated by treating full-thickness cutaneous wounds in a diabetic mouse model, indicating the remarkable prospects of i-SMD in wound management and other related biomedical fields.     

Super-Strong and Super-Stiff Chitosan Filaments with Highly Ordered Hierarchical Structure

Currently, the world is facing the problems of the gradual depletion of non-renewable fossil resources and the severe harm of non-degradable plastic waste to the land and marine ecological environment. Because of the rapid increase in the demand for fiber materials, the development of high-performance biomass-based fibers has emerged as an important research topic to reduce the reliance on petroleum-based synthetic fibers. In this study, a novel green wet-spinning strategy is used for the fabrication of super-strong and super-stiff chitosan filaments from an aqueous KOH/urea solution using a two-step drawing process. The highly ordered hierarchical structure of the resulting filaments contributes to their excellent mechanical properties. The tensile strength and Young's modulus of the chitosan filaments are 878 ± 123 MPa and 44.7 ± 12.3 GPa, respectively, and these values are comparable to those of spider silk and bacterial cellulose. The chitosan filaments prepared in this study are superior to low-density steel in terms of the specific strength and modulus. The green and scalable strategy proposed in this study will broaden the application range of chitosan filaments in flexible bioelectronics, biomaterials, and textiles.     

Flexible Piezoresistive Sensor Patch Enabling Ultralow Power Cuffless Blood Pressure Measurement

Noninvasive and real‐time cuffless blood pressure (BP) measurement realizes the idea of unobtrusive and continuous BP monitoring which is essential for diagnosis and prevention of cardiovascular diseases associated with hypertension. In this paper, a wearable sensor patch system that integrates flexible piezoresistive sensor (FPS) and epidermal electrocardiogram (ECG) sensors for cuffless BP measurement is presented. By developing parametric models on the FPS sensing mechanism and optimizing operational conditions, a highly stable epidermal pulse monitoring method is established and beat‐to‐beat BP measurement from the ECG and epidermal pulse signals is demonstrated. In particular, this study highlights the compromise between sensor sensitivity and signal stability. As compared with the current optical‐based cuffless BP measurement devices, the sensing patch requires much lower power consumption (3 nW) and is capable of detecting subtle physiological signal variations, e.g., pre and postexercises, thus providing a promising solution for low‐power, real‐time, and home‐based BP monitoring.     

Conductive Cellulose Bio-Nanosheets Assembled Biostable Hydrogel for Reliable Bioelectronics

Biostable electronic materials that can maintain their super mechanical and conductive properties, even when exposed to biofluids, are the fundamental basis for designing reliable bioelectronic devices. Herein, cellulose-derived conductive 2D bio-nanosheets as electronic base materials are developed and assembled into a conductive hydrogel with ultra-high biostability, capable of surviving in harsh physiological environments. The bio-nanosheets are synthesized by guiding the in situ regeneration of cellulose crystal into a 2D planar structure using the polydopamine-reduced-graphene oxide as supporting templates. The nanosheet-assembled hydrogel exhibits stable electrical and mechanical performances after undergoing aqueous immersion and in vivo implantation. Thus, the hydrogel-based bioelectronic devices are able to conformally integrate with the human body and stably record electrophysiological signals. Owing to its tissue affinity, the hydrogel further serves as an “E-skin,” which employs electrotherapy to aid in the faster healing of chronic wounds in diabetic mice through transcutaneous electrical stimulation. The nanosheet-assembled biostable, conductive, flexible, and cell/tissue affinitive hydrogel lays a foundation for designing electronically and mechanically reliable bioelectronic devices.     

Flexible Breathable Nanomesh Electronic Devices for On‐Demand Therapy

Flexible electronics are drawing tremendous interest for various applications in wearable healthcare biomonitoring, on‐demand therapy, and human–machine interactions. However, conventional plastic substrates with uncomfortableness, mechanical mismatches, and impermeability have limited the application of flexible on‐skin electronic devices for healthcare biomonitoring and on‐demand therapy. Herein, flexible breathable electronic devices with the capabilities of real‐time temperature sensing and timely on‐demand anti‐infection therapy at wound sites are presented. These devices are assembled from a crosslinked electrospun moxifloxacin hydrochloride (MOX)‐loaded thermoresponsive polymer nanomesh film with a conductive pattern. The conductive polymer nanomesh film demonstrates excellent flexibility, reliable breathability, and robust environmental stability. Furthermore, the assembled temperature sensor displays a linear relationship between the electrical resistance and temperature, potentially enabling real‐time biomonitoring of tissue temperature at the wound site. Smart artificial electronic skins (E‐skins) are assembled from the thermoresponsive polymer nanomesh film for spatial touching sensing mapping of temperature changes. Furthermore, the flexible temperature sensor is coupled with a wireless transmitter for real‐time wireless temperature monitoring. Notably, the thermoresponsive polymer nanomesh film can also be assembled as a highly efficient flexible heater to trigger the on‐demand release of antibiotics loaded in the fibers to eliminate bacterial colonization in the wound site once infection has occurred.     

MXene/Fluoropolymer-Derived Laser-Carbonaceous All-Fibrous Nanohybrid Patch for Soft Wearable Bioelectronics

While state-of-the-art skin-adhering fibrous electrodes have distinct benefits in personal wearable bioelectronics, considerable challenges persist in the production of fibrous-based soft conductive biosensing nanomaterials and their integration into efficient multisensing platforms. Here, an electrochemical-electrophysiological multimodal biosensing patch based on MXene/fluoropolymer nanofiber-derived hierarchical porous TiO₂ nanocatalyst interconnected 3D fibrous carbon nanohybrid electrodes is reported. The nanohybrid electrode is produced via a one-step laser carbonaceous thermal oxidation, resulting in excellent elctroconductivity (sheet resistance = 15.6 Ω sq⁻¹), rich active edges for effective electron transmission, and abundant support for enzyme immobilization. The features are attributed to three synergistic effects: i) conductivity of the interior, unoxidized MXene layers, ii) quick heterogeneous electron transmission of the exterior TiO₂ nanoparticles, and iii) the porous disordered carbon's electron “bridge” effects. Based on the foregoing, the nanohybrid modified biosensing patch integrated into textile is demonstrated to be capable of simultaneously and precisely monitoring sweat glucose with pH adjustment (sensitivity of 77.12 µA mm ⁻¹ cm⁻² within physiological concentrations of 0.01–2 × 10⁻³ m ) and electrocardiogram signals (signal-to-noise ratio = 37.63 dB). This novel approach paves the way for controlled investigations of the nanohybrid, for several functionalization and design options, and for the mass manufacturing capabilities required in real-world applications.     

Seriography‐Guided Reduction of Graphene Oxide Biopapers for Wearable Sensory Electronics

Novel nacre‐mimic bio‐nanocomposites, such as graphene‐based laminates, are pushing the boundaries of strength and toughness as flexible engineering materials. Translating these material advances to functional flexible electronics requires methods for generating print‐scalable microcircuits (conductive elements surrounded by dielectric) into these strong, tough, lightweight bio‐nanocomposites. Here, a new paradigm for printing flexible electronics by employing facile, eco‐friendly seriography to confine the reduction of graphene oxide biopapers reinforced by silk interlayers is presented. Well‐defined, micropatterned regions on the biopaper are chemically reduced, generating a 10⁶ increase in conductivity (up to 10⁴ S m^?1). Flexible, robust graphene‐silk circuits are showcased in diverse applications such as resistive moisture sensors and capacitive proximity sensors. Unlike conductive (i.e., graphene‐ or Ag nanoparticle‐loaded) inks printed onto substrates, seriography‐guided reduction does not create mechanically weak interfaces between dissimilar materials and does not require the judicious formation of ink. The unimpaired functionality of printed‐in graphene‐silk microcircuits after thousands of punitive folding cycles and chemical attack by harsh solvents is demonstrated. This novel approach provides a low‐cost, portable solution for printing micrometer‐scale conductive features uniformly across large areas (>hundreds of cm²) in layered composites for applications including wearable health monitors, electronic skin, rollable antennas, and conformable displays.     

Stretchable Twisted‐Pair Transmission Lines for Microwave Frequency Wearable Electronics

Stretchable electrical interconnects based on serpentines combined with elastic materials are utilized in various classes of wearable electronics. However, such interconnects are primarily for direct current or low‐frequency signals and incompatible with microwave electronics that enable wireless communication. In this paper, design and fabrication procedures are described for stretchable transmission line capable of delivering microwave signals. The stretchable transmission line has twisted‐pair design integrated into thin‐film serpentine microstructure to minimize electromagnetic interference, such that the line's performance is minimally affected by the environment in close proximity, allowing its use in thin‐film bioelectronics, such as the epidermal electronic system. Detailed analysis, simulations, and experimental results show that the stretchable transmission line has negligible changes in performance when stretched and is operable on skin through suppressed radiated emission achieved with the twisted‐pair geometry. Furthermore, stretchable microwave low‐pass filter and band‐stop filter are demonstrated using the twisted‐pair structure to show the feasibility of the transmission lines as stretchable passive components. These concepts form the basic elements used in the design of stretchable microwave components, circuits, and subsystems performing important radio frequency functionalities, which can apply to many types of stretchable bioelectronics for radio transmitters and receivers.     

Muscle-Inspired MXene Conductive Hydrogels with Anisotropy and Low-Temperature Tolerance for Wearable Flexible Sensors and Arrays

Conductive hydrogels as flexible electronic devices, not only have unique attractions but also meet the basic need of mechanical flexibility and intelligent sensing. How to endow anisotropy and a wide application temperature range for traditional homogeneous conductive hydrogels and flexible sensors is still a challenge. Herein, a directional freezing method is used to prepare anisotropic MXene conductive hydrogels that are inspired by ordered structures of muscles. Due to the anisotropy of MXene conductive hydrogels, the mechanical properties and electrical conductivity are enhanced in specific directions. The hydrogels have a wide temperature resistance range of −36 to 25 °C through solvent substitution. Thus, the muscle-inspired MXene conductive hydrogels with anisotropy and low-temperature resistance can be used as wearable flexible sensors. The sensing signals are further displayed on the mobile phone as images through wireless technology, and images will change with the collected signals to achieve motion detection. Multiple flexible sensors are also assembled into a 3D sensor array for detecting the magnitude and spatial distribution of forces or strains. The MXene conductive hydrogels with ordered orientation and anisotropy are promising for flexible sensors, which have broad application prospects in human–machine interface compatibility and medical monitoring.     

Skin‐Inspired Antibacterial Conductive Hydrogels for Epidermal Sensors and Diabetic Foot Wound Dressings

Recently, artificial intelligence research has driven the development of stretchable and flexible electronic systems. Conductive hydrogels are a class of soft electronic materials that have emerging applications in wearable and implantable biomedical devices. However, current conductive hydrogels possess fundamental limitations in terms of their antibacterial performance and a mechanical mismatch with human tissues, which severely limits their applications in biological interfaces. Here, inspired by animal skin, a conductive hydrogel is fabricated from a supramolecular assembly of polydopamine decorated silver nanoparticles (PDA@Ag NPs), polyaniline, and polyvinyl alcohol, namely PDA@Ag NPs/CPHs. The resultant hydrogel has many desirable features, such as tunable mechanical and electrochemical properties, eye‐catching processability, good self‐healing ability as well as repeatable adhesiveness. Remarkably, PDA@Ag NPs/CPHs exhibit broad antibacterial activity against Gram‐negative and Gram‐positive bacteria. The potential application of this versatile hydrogel is demonstrated by monitoring large‐scale movements of the human body in real time. In addition, PDA@Ag NPs/CPHs have a significant therapeutic effect on diabetic foot wounds by promoting angiogenesis, accelerating collagen deposition, inhibiting bacterial growth, and controlling wound infection. To the best of the authors' knowledge, this is the first time that conductive hydrogels with antibacterial ability are developed for use as epidermal sensors and diabetic foot wound dressing.     

Calcium‐Modified Silk as a Biocompatible and Strong Adhesive for Epidermal Electronics

With the increasing interest and demand for epidermal electronics, a strong interface between a sensor and a biological surface is essential, yet achieving such interface is still a challenge. Here, a calcium (Ca)‐modified biocompatible silk fibroin as a strong adhesive for epidermal electronics is proposed and the physical principles behind its interfacial and adhesive properties are reported. A strong adhesive characteristic (>800 N m^?1) is observed because of the increase in both viscoelastic property and mechanical interlocking through the incorporation of Ca ions. Furthermore, additional key characteristics of the Ca‐modified silk: reusability, stretchability, biocompatibility, and conductivity, are reported. These characteristics enable a wide range of applications as demonstrated in four epidermal electronic systems: capacitive touch sensor, resistive strain sensor, hydrogel‐based drug delivery, and electrocardiogram monitoring sensor. As a reusable, biocompatible, conductive, and strong adhesive with water‐degradability, the Ca‐modified silk adhesive is a promising candidate for the next‐generation adhesive for epidermal biomedical sensors.     

Organic Electrochemical Transistor Common-Source Amplifier for Electrophysiological Measurements

The portability of physiological monitoring has necessitated the biocompatibility of components used in circuitry local to biological environments. A key component in processing circuitry is the linear amplifier. Amplifier circuit topologies utilize transistors, and recent advances in bioelectronics have focused on organic electrochemical transistors (OECTs). OECTs have shown the capability to transduce physiological signals at high signal-to-noise ratios. In this study high-performance interdigitated electrode OECTs are implemented in a common source linear amplifier topology. Under the constraints of OECT operation, stable circuit component parameters are found, and OECT geometries are varied to determine the best amplifier performance. An equation is formulated which approximates transistor behavior in the linear, nonlinear, and saturation regimes. This equation is used to simulate the amplifier response of the circuits with the best performing OECT geometries. The amplifier figures of merit, including distortion characterizations, are then calculated using physical and simulation measurements. Based on the figures of merit, prerecorded electrophysiological signals from spreading depolarizations, electrocorticography, and electromyography fasciculations are inputted into an OECT linear amplifier. Using frequency filtering, the primary features of events in the bioelectric signals are resolved and amplified, demonstrating the capability of OECT amplifiers in bioelectronics.     

Highly Stretchable,Elastic, and Ionic Conductive Hydrogel for Artificial Soft Electronics

High conductivity, large mechanical strength, and elongation are important parameters for soft electronic applications. However, it is difficult to find a material with balanced electronic and mechanical performance. Here, a simple method is developed to introduce ion‐rich pores into strong hydrogel matrix and fabricate a novel ionic conductive hydrogel with a high level of electronic and mechanical properties. The proposed ionic conductive hydrogel is achieved by physically cross‐linking the tough biocompatible polyvinyl alcohol (PVA) gel as the matrix and embedding hydroxypropyl cellulose (HPC) biopolymer fibers inside matrix followed by salt solution soaking. The wrinkle and dense structure induced by salting in PVA matrix provides large stress (1.3 MPa) and strain (975%). The well‐distributed porous structure as well as ion migration–facilitated ion‐rich environment generated by embedded HPC fibers dramatically enhances ionic conductivity (up to 3.4 S m^?1, at f = 1 MHz). The conductive hybrid hydrogel can work as an artificial nerve in a 3D printed robotic hand, allowing passing of stable and tunable electrical signals and full recovery under robotic hand finger movements. This natural rubber‐like ionic conductive hydrogel has a promising application in artificial flexible electronics.     

Strong Reduced Graphene Oxide Coated Bombyx mori Silk

Bombyx mori silks possess great potential in textile industries due to the large-scale green production. However, the demand for silks with functional as well as mechanical properties are continuously rising due to the emergence of other functional textiles. It remains a great challenge to functionalize natural silk and simultaneously improve its mechanical properties. Inspired by the relationship between natural core–sheath structure and mechanical properties of cocoon silk, the application of a thin reduced graphene oxide (rGO) layer coated B. mori silk (GS) is shown via hydrogen interfacial interaction. The resultant rGO-coated silk exhibits a remarkable tensile strength of 1137.7 MPa and toughness of 304.5 MJ m⁻³, which are 1.9 and 2.6 times higher than that of pure B. mori silk, respectively. Moreover, the GS shows a high electrical conductivity of 0.37 S m⁻¹ with great thermal and deformation sensitivity. The bioinspired approach provides a universal and facile strategy for functionalizing natural fibers by applying rGO nanosheets surface coating.     

Emerging Soft Conductors for Bioelectronic Interfaces

Bidirectional interfacing between electrodes and biological systems has enabled diagnostics and therapeutics in modern medicine; however, the inherent dissimilarity between the soft, ion‐rich, dynamic biological tissues and the rigid, dry, static electronic systems hinders the establishment of effective and reliable bioelectronic interfaces. In the past decade, the scope of flexible/stretchable electronics has been broadened into bioelectronics owing to the need of implementation of various biocompatible soft conductors. Herein, the basic requirements for the construction of both epidermal and implantable bioelectronic interfaces utilizing soft materials are discussed, the most recent progress in the development of soft conductors, which are customized to interface with skin and other tissues, are summarized. An outlook into the remaining obstacles is provided and possible strategies to facilitate technological advances in bioelectronics are also outlined.     

Spinning Beta Silks Requires Both pH Activation and Extensional Stress

Synthetic silk production has undergone significant technological and commercial advances over the past 5 years, with fibers from most labs and companies now regularly matching the properties of natural silk by one metric or another. Yet the fundamental links between silk protein processing and performance remain largely unresolved and fiber optimization is commonly achieved through non-natural methods. In an effort to address this challenge, data that closes this loop of processing and performance is presented by spinning a native silk feedstock ex vivo into a near-native fiber using just two naturally occurring parameters; pH activation and extensional flow (i.e., spinning rate). This allows us to link previous experimental and modelling hypothesis surrounding silk's pH responsiveness directly to multiscale hierarchical structure development during spinning. Finally, fibers that match, and then exceed, natural silk's mechanical properties are spun and understood by rate of work input. This approach not only provides energetic insights into natural silk spinning and controlled protein denaturation, but is believed will help interpret and improve synthetic silk processing. Ultimately, it is hoped that these results will contribute towards novel bioinspired energy-efficient processing strategies that are driven by work input optimization and where excellent mechanical properties are self-emergent.     

Bioinspired MXene-Based Piezoresistive Sensor with Two-stage Enhancement for Motion Capture (Adv. Funct. Mater. 18/2023)

Structured piezoresistive membranes are compelling building blocks for wearable bioelectronics. However, the poor structural compressibility of conventional microstructures leads to rapid saturation of detection range and low sensitivity of piezoresistive devices, limiting their commercial applications. Herein, a bioinspired MXene-based piezoresistive device is reported, which can effectively boost the sensitivity while broadening the response range by architecting intermittent villus-like microstructures. Benefitting from the two-stage amplification effect of this intermittent architecture, the developed MXene-based piezoresistive bioelectronics exhibit a high sensitivity of 461 kPa⁻¹ and a broad pressure detection range of up to 311 kPa, which are about 20 and 5 times higher than that of the homogeneous microstructures, respectively. Cooperating with the deep-learning algorithm, the designed bioelectronics can effectively capture complex human movements and precisely identify human motion with a high recognition accuracy of 99%. Evidently, this intermittent architecture of biomimetic strategy may pave a promising avenue to overcome the limitation of rapid saturation and low sensitivity in piezoresistive bioelectronics, and provide a general way to promote its large-scale applications.