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.

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.

A Water-Resistant, Self-Healing Encapsulation Layer for a Stable, Implantable Wireless Antenna.

Polymers for implantable devices are desirable for biomedical engineering applications. This study introduces a water-resistant, self-healing fluoroelastomer (SHFE) as an encapsulation material for antennas. The SHFE exhibits a tissue-like modulus (approximately 0.4 MPa), stretchability (at least 450%, even after self-healing in an underwater environment), self-healability, and water resistance (WVTR result: 17.8610 g m-2 day-1). Further, the SHFE is self-healing in underwater environments via dipole-dipole interactions, such that devices can be protected from the penetration of biofluids and withstand external damage. With the combination of the SHFE and antennas designed to operate inside the body, we fabricated implantable, wireless antennas that can transmit information from inside the body to a reader coil that is outside. For antennas designed considering the dielectric constant, the uniformity of the encapsulation layer is crucial. A uniform and homogeneous interface is formed by simply overlapping two films. This study demonstrated the possibility of wireless communication in vivo through experiments on rodents for 4 weeks, maintaining the maximum communication distance (15 mm) without chemical or physical deformation in the SHFE layer. This study illustrates the applicability of fluoroelastomers in vivo and is expected to contribute to realizing the stable operation of high-performance implantable devices.

Reversible electrical percolation in a stretchable and self-healable silver-gradient nanocomposite bilayer.

The reversibly stable formation and rupture processes of electrical percolative pathways in organic and inorganic insulating materials are essential prerequisites for operating non-volatile resistive memory devices. However, such resistive switching has not yet been reported for dynamically cross-linked polymers capable of intrinsic stretchability and self-healing. This is attributable to the uncontrollable interplay between the conducting filler and the polymer. Herein, we present the development of the self-healing, stretchable, and reconfigurable resistive random-access memory. The device was fabricated via the self-assembly of a silver-gradient nanocomposite bilayer which is capable of easily forming the metal-insulator-metal structure. To realize stable resistive switching in dynamic molecular networks, our device features the following properties: i) self-reconstruction of nanoscale conducting fillers in dynamic hydrogen bonding for self-healing and reconfiguration and ii) stronger interaction among the conducting fillers than with polymers for the formation of robust percolation paths. Based on these unique features, we successfully demonstrated stable data storage of cardiac signals, damage-reliable memory triggering system using a triboelectric energy-harvesting device, and touch sensing via pressure-induced resistive switching.

Electrostatic-Mechanical Synergistic In Situ Multiscale Tissue Adhesion for Sustainable Residue-Free Bioelectronics Interfaces.

Recent studies on soft adhesives have sought to deeply understand how their chemical or mechanical structures interact strongly with living tissues. The aim is to optimally address the unmet needs of patients with acute or chronic diseases. Synergistic adhesion involving both electrostatic (hydrogen bonds) and mechanical interactions (capillarity-assisted suction stress) seems to be effective in overcoming the challenges associated with long-term unstable coupling to tissues. Here, an electrostatically and mechanically synergistic mechanism of residue-free, sustainable, in situ tissue adhesion by implementing hybrid multiscale architectonics. To deduce the mechanism, a thermodynamic model based on a tailored multiscale combinatory adhesive is proposed. The model supports the experimental results that the thermodynamically controlled swelling of the nanoporous hydrogel embedded in the hierarchical elastomeric structure enhances biofluid-insensitive, sustainable, in situ adhesion to diverse soft, slippery, and wet organ surfaces, as well as clean detachment in the peeling direction. Based on the robust tissue adhesion capability, universal reliable measurements of electrophysiological signals generated by various tissues, ranging from rodent sciatic nerve, the muscle, brain, and human skin, are successfully demonstrated.

Lead-Sealed Stretchable Underwater Perovskite-Based Optoelectronics via Self-Recovering Polymeric Nanomaterials.

To harness the full potential of halide perovskite based optoelectronics, biological safety, compatibility with flexible/stretchable platforms, and operational stability must be guaranteed. Despite substantial efforts, none has come close to providing a solution that encompasses all of these requirements. To address these issues, we devise a multifunctional encapsulation scheme utilizing hydrogen bond-based self-recovering polymeric nanomaterials as an alternative for conventional glass-based encapsulation. We show that Pb in physically damaged halide perovskite solar cells can be completely contained within the self-recovering encapsulation upon submersion in a simulated rain bath, as indicated by in vitro cytotoxicity tests. In addition, self-recovering encapsulation accommodates stable device operation upon casual bending and even stretching, which is in stark contrast to conventional glass-based encapsulation schemes. We also demonstrate the concept of assembling user-defined scalable modular optoelectronics based on halide perovskite solar cells and light emitting diodes through the use of self-recovering conductive nanocomposites. Finally, long-term operational stability of over 1000 h was achieved under harsh accelerated conditions (50 °C/50% RH and 85 °C/0% RH) with the incorporation of an ultrathin atomic layer deposited TiO2 barrier underneath the multifunctional encapsulation. In light of these merits, the encapsulation scheme based on self-recovering polymeric nanomaterials is proposed as a simple, but practical solution to a multifaceted challenge in the field of halide perovskites.

A Bioinspired Stretchable Sensory-Neuromorphic System.

Conventional stretchable electronics that adopt a wavy design, a neutral mechanical plane, and conformal contact between abiotic and biotic interfaces have exhibited diverse skin-interfaced applications. Despite such remarkable progress, the evolution of intelligent skin prosthetics is challenged by the absence of the monolithic integration of neuromorphic constituents into individual sensing and actuating components. Herein, a bioinspired stretchable sensory-neuromorphic system, comprising an artificial mechanoreceptor, artificial synapse, and epidermal photonic actuator is demonstrated; these three biomimetic functionalities correspond to a stretchable capacitive pressure sensor, a resistive random-access memory, and a quantum dot light-emitting diode, respectively. This system features a rigid-island structure interconnected with a sinter-free printable conductor, which is optimized by controlling the evaporation rate of solvent (≈160% stretchability and ≈18 550 S cm-1 conductivity). Devised design improves both areal density and structural reliability while avoiding the thermal degradation of heat-sensitive stretchable electronic components. Moreover, even in the skin deformation range, the system accurately recognizes various patterned stimuli via an artificial neural network with training/inferencing functions. Therefore, the new bioinspired system is expected to be an important step toward implementing intelligent wearable electronics.

A Soft Pressure Sensor Array Based on a Conducting Nanomembrane.

Although skin-like pressure sensors exhibit high sensitivity with a high performance over a wide area, they have limitations owing to the critical issue of being linear only in a narrow strain range. Various strategies have been proposed to improve the performance of soft pressure sensors, but such a nonlinearity issue still exists and the sensors are only effective within a very narrow strain range. Herein, we fabricated a highly sensitive multi-channel pressure sensor array by using a simple thermal evaporation process of conducting nanomembranes onto a stretchable substrate. A rigid-island structure capable of dissipating accumulated strain energy induced by external mechanical stimuli was adopted for the sensor. The performance of the sensor was precisely controlled by optimizing the thickness of the stretchable substrate and the number of serpentines of an Au membrane. The fabricated sensor exhibited a sensitivity of 0.675 kPa-1 in the broad pressure range of 2.3-50 kPa with linearity (~0.990), and good stability (>300 Cycles). Finally, we successfully demonstrated a mapping of pressure distribution.

Durable and Fatigue-Resistant Soft Peripheral Neuroprosthetics for In Vivo Bidirectional Signaling.

Soft neuroprosthetics that monitor signals from sensory neurons and deliver motor information can potentially replace damaged nerves. However, achieving long-term stability of devices interfacing peripheral nerves is challenging, since dynamic mechanical deformations in peripheral nerves cause material degradation in devices. Here, a durable and fatigue-resistant soft neuroprosthetic device is reported for bidirectional signaling on peripheral nerves. The neuroprosthetic device is made of a nanocomposite of gold nanoshell (AuNS)-coated silver (Ag) flakes dispersed in a tough, stretchable, and self-healing polymer (SHP). The dynamic self-healing property of the nanocomposite allows the percolation network of AuNS-coated flakes to rebuild after degradation. Therefore, its degraded electrical and mechanical performance by repetitive, irregular, and intense deformations at the device-nerve interface can be spontaneously self-recovered. When the device is implanted on a rat sciatic nerve, stable bidirectional signaling is obtained for over 5 weeks. Neural signals collected from a live walking rat using these neuroprosthetics are analyzed by a deep neural network to predict the joint position precisely. This result demonstrates that durable soft neuroprosthetics can facilitate collection and analysis of large-sized in vivo data for solving challenges in neurological disorders.

Adaptive self-healing electronic epineurium for chronic bidirectional neural interfaces.

Realizing a clinical-grade electronic medicine for peripheral nerve disorders is challenging owing to the lack of rational material design that mimics the dynamic mechanical nature of peripheral nerves. Electronic medicine should be soft and stretchable, to feasibly allow autonomous mechanical nerve adaptation. Herein, we report a new type of neural interface platform, an adaptive self-healing electronic epineurium (A-SEE), which can form compressive stress-free and strain-insensitive electronics-nerve interfaces and enable facile biofluid-resistant self-locking owing to dynamic stress relaxation and water-proof self-bonding properties of intrinsically stretchable and self-healable insulating/conducting materials, respectively. Specifically, the A-SEE does not need to be sutured or glued when implanted, thereby significantly reducing complexity and the operation time of microneurosurgery. In addition, the autonomous mechanical adaptability of the A-SEE to peripheral nerves can significantly reduce the mechanical mismatch at electronics-nerve interfaces, which minimizes nerve compression-induced immune responses and device failure. Though a small amount of Ag leaked from the A-SEE is observed in vivo (17.03 ppm after 32 weeks of implantation), we successfully achieved a bidirectional neural signal recording and stimulation in a rat sciatic nerve model for 14 weeks. In view of our materials strategy and in vivo feasibility, the mechanically adaptive self-healing neural interface would be considered a new implantable platform for a wide range application of electronic medicine for neurological disorders in the human nervous system.

A Skin-Conformal, Stretchable, and Breathable Fiducial Marker Patch for Surgical Navigation Systems.

Augmented reality (AR) surgical navigation systems have attracted considerable attention as they assist medical professionals in visualizing the location of ailments within the human body that are not readily seen with the naked eye. Taking medical imaging with a parallel C-shaped arm (C-arm) as an example, surgical sites are typically targeted using an optical tracking device and a fiducial marker in real-time. These markers then guide operators who are using a multifunctional endoscope apparatus by signaling the direction or distance needed to reach the affected parts of the body. In this way, fiducial markers are used to accurately protect the vessels and nerves exposed during the surgical process. Although these systems have already shown potential for precision implantation, delamination of the fiducial marker, which is a critical component of the system, from human skin remains a challenge due to a mechanical mismatch between the marker and skin, causing registration problems that lead to poor position alignments and surgical degradation. To overcome this challenge, the mechanical modulus and stiffness of the marker patch should be lowered to approximately 150 kPa, which is comparable to that of the epidermis, while improving functionality. Herein, we present a skin-conformal, stretchable yet breathable fiducial marker for the application in AR-based surgical navigation systems. By adopting pore patterns, we were able to create a fiducial marker with a skin-like low modulus and breathability. When attached to the skin, the fiducial marker was easily identified using optical recognition equipment and showed skin-conformal adhesion when stretched and shrunk repeatedly. As such, we believe the marker would be a good fiducial marker candidate for patients under surgical navigation systems.

An Ultrastretchable and Self-Healable Nanocomposite Conductor Enabled by Autonomously Percolative Electrical Pathways.

Both self-healable conductors and stretchable conductors have been previously reported. However, it is still difficult to simultaneously achieve high stretchability, high conductivity, and self-healability. Here, we observed an intriguing phenomenon, termed "electrical self-boosting", which enables reconstructing of electrically percolative pathways in an ultrastretchable and self-healable nanocomposite conductor (over 1700% strain). The autonomously reconstructed percolative pathways were directly verified by using microcomputed tomography and in situ scanning electron microscopy. The encapsulated nanocomposite conductor shows exceptional conductivity (average value: 2578 S cm-1; highest value: 3086 S cm-1) at 3500% tensile strain by virtue of efficient strain energy dissipation of the self-healing polymer and self-alignment and rearrangement of silver flakes surrounded by spontaneously formed silver nanoparticles and their self-assembly in the strained self-healing polymer matrix. In addition, the conductor maintains high conductivity and stretchability even after recovered from a complete cut. Besides, a design of double-layered conductor enabled by the self-bonding assembly allowed a conducting interface to be located on the neutral mechanical plane, showing extremely durable operations in a cyclic stretching test. Finally, we successfully demonstrated that electromyogram signals can be monitored by our self-healable interconnects. Such information was transmitted to a prosthetic robot to control various hand motions for robust interactive human-robot interfaces.