Implantable, Degradable, Therapeutic Terahertz Metamaterial Devices.

Metamaterial (MM) sensors and devices, usually consisting of artificially structured composite materials with engineered responses that are mainly determined by the unit structure rather than the bulk properties or composition, offer new functionalities not readily available in nature. A set of implantable and resorbable therapeutic MM devices at terahertz (THz) frequencies are designed and fabricated by patterning magnesium split ring resonators on drug-loaded silk protein substrates with controllable device degradation and drug release rates. To demonstrate proof-of-concept, a set of silk-based, antibiotics-loaded MM devices, which can serve as degradable antibacterial skin patches with capabilities to monitor drug-release in real time are fabricated. The extent of drug release, which correlates with the degradation of the MM skin patch, can be monitored by analyzing the resonant responses in reflection during degradation using a portable THz camera. Animal experiments are performed to demonstrate the in vivo degradation process and the efficacy of the devices for antibacterial treatment. Thus, the implantable and resorbable therapeutic MM devices do not need to be retrieved once implanted, providing an appealing alternative for in-vivo sensing and in situ treatment applications.

Hyperbolic Phonon Polaritons in Suspended Hexagonal Boron Nitride.

Highly confined and low-loss hyperbolic phonon polaritons in hexagonal boron nitride possess properties analogous to surface plasmon polaritons, but with enhanced confinement and lower loss. Their properties have been so far mostly studied on dielectric substrates, which provide an asymmetric environment for polariton propagation, and add to damping. In this work, we investigate hyperbolic phonon polaritons over suspended hexagonal boron nitride, showing remarkable properties, including elongated polariton wavelength and reduced damping, up to 18% lower compared to dielectric-backed samples. We use real-space nanoimaging of the polaritons in hexagonal boron nitride to demonstrate and visualize these effects. Our results indicate that suspended boron nitride offers better figures of merit for polariton transport, which are generalizable to other polaritonic materials, and they may be explored in heterostructures for advanced nanophotonic applications.

Photo-induced terahertz near-field dynamics of graphene/InAs heterostructures.

In this letter, we report optical pump terahertz (THz) near-field probe (n-OPTP) and optical pump THz near-field emission (n-OPTE) experiments of graphene/InAs heterostructures. Near-field imaging contrasts between graphene and InAs using these newly developed techniques as well as spectrally integrated THz nano-imaging (THz s-SNOM) are systematically studied. We demonstrate that in the near-field regime (λ/6000), a single layer of graphene is transparent to near-IR (800 nm) optical excitation and completely "screens" the photo-induced far-infrared (THz) dynamics in its substrate (InAs). Our work reveals unique frequency-selective ultrafast dynamics probed at the near field. It also provides strong evidence that n-OPTE nanoscopy yields contrast that distinguishes single-layer graphene from its substrate.

Three-dimensional finite element analysis of silk protein rod implantation after core decompression for osteonecrosis of the femoral head.

BACKGROUND: Several methods are available for the treatment of early-stage osteonecrosis of the femoral head. Core decompression with implantation is a widely-used treatment. However, no single implant is recognized as the most effective way to prevent disease progression. Silk has high strength and resiliency. This study explored the possibility of a strong and resilient silk protein biomaterial as a new alternative implant. METHODS: We investigated the biomechanical properties of the silk protein material by regular compression, torsion, and three-point bending tests. We established three-dimensional finite element models of different degrees of femoral head osteonecrosis following simple core decompression, fibula implantation, porous tantalum rod implantation, and silk protein rod implantation. Finally, we compared the differences in displacement and surface stress under load at the femoral head weight-bearing areas between these models. RESULTS: The elastic modulus and shear modulus of the silk protein material was 0.49GPa and 0.66GPa, respectively. Three-dimensional finite element analyses demonstrated less displacement and surface stress at the femoral head weight-bearing areas following silk protein rod implantation compared to simple core decompression (p < 0.05), regardless of the extent of osteonecrosis. No differences were noted in the surface deformation or surface stress of the femoral head weight-bearing areas following silk protein rod, fibula or tantalum rod implantation (p > 0.05). CONCLUSIONS: When compared with simple core decompression, silk protein rod implantation demonstrated less displacement and surface stress at the femoral head weight-bearing area, but more than fibula or tantalum rod implantation. Similar effects on the surface stress of the femoral head between the silk rod, fibula and tantalum rod implantations, combined with additional modifiable properties support the use of silk protein as a suitable biomaterial in osteonecrosis surgery.

Internal Nanostructure Diagnosis with Hyperbolic Phonon Polaritons in Hexagonal Boron Nitride.

Imaging materials and inner structures with resolution below the diffraction limit has become of fundamental importance in recent years for a wide variety of applications. We report subdiffractive internal structure diagnosis of hexagonal boron nitride by exciting and imaging hyperbolic phonon polaritons. On the basis of their unique propagation properties, we are able to accurately locate defects in the crystal interior with nanometer resolution. The precise location, size, and geometry of the concealed defects are reconstructed by analyzing the polariton wavelength, reflection coefficient, and their dispersion. We have also studied the evolution of polariton reflection, transmission, and scattering as a function of defect size and photon frequency. The nondestructive high-precision polaritonic structure diagnosis technique introduced here can be also applied to other hyperbolic or waveguide systems and may be deployed in the next-generation biomedical imaging, sensing, and fine structure analysis.

"Print-to-pattern": Silk-Based Water Lithography.

The requirement of nontoxic and versatile manufacturing frameworks for biologically relevant applications has imposed significant constraints on the choice of functional materials and the complementary fabrication tools. In this context, silk is actively studied, thanks to its mechanical robustness, biocompatibility, wide availability, aqueous processing conditions, and ease of functionalization. The inherent matching between the water solubility of silk and the aqueous inks of the inkjet printing (IJP) process has derived a biofriendly and versatile "print-to-pattern" scheme-termed silk-based water lithography-toward scalable functional biomanufacturing. The deposition mode of IJP and the etching effect of silk film by water features a dual tone fabrication where functional molecules are dispensed additively, while the silk film is patterned in a "subtractive" fashion. Such versatility and scalability pave the way to a wide range of opportunities in the biomedical field.

Self-Powered Multifunctional Transient Bioelectronics.

Controllable degradation and excellent biocompatibility during/after a lifetime endow emerging transient electronics with special superiority in implantable biomedical applications. Currently, most of these devices need external power sources, limiting their real-world utilizations. Optimizing existing bioresorbable electronic devices requires natural-material-based construction and, more importantly, diverse or even all-in-one multifunctionalization. Herein, silk-based implantable, biodegradable, and multifunctional systems, self-powered with transient triboelectric nanogenerators (T2 ENGs), for real-time in vivo monitoring and therapeutic treatments of epileptic seizures, are reported. These T2 ENGs are of customizable in vitro/in vivo operating life and biomechanical sensitivity via the adjustments of silk molecular size, surface structuralization, and device configuration. Functions, such as drug delivery and structural-integrity optical readout (parallel to electronic signals), are enabled for localized anti-infection and noninvasive degradation indication, respectively. A proof-of-principle wireless system is built with mobile-device readout and "smart" treatment triggered by specific symptoms (i.e., epilepsy), exhibiting the practical potential of these silk T2 ENGs as self-powered, transient, and multifunctional implantable bioelectronic platforms.

Direct Optical Patterning of Metal-Organic Frameworks via Photoacid-Induced Etching.

Metal-organic frameworks (MOFs) are a class of porous materials constructed from organic linkers and inorganic building blocks. Coordinative competition labilizes some MOFs under harsh chemical conditions because of their weak bonding. However, instability is not always a negative property of a material. In this study, we demonstrated the use of the acidic lability of MOFs for direct optical patterning. The controllable acid release from the photoacid generator at the exposed area causes bond cleavage between the linkers and metal ions/clusters, leading to solubility changes and pattern formation after development. This process avoids redundant steps and possible contamination in traditional photolithography, while maintaining the original properties of patterned MOFs. The preserved porosity and crystallinity promoted the development of MOFs for gas sensors and solid displays.

Water-Responsive Self-Contractive Silk-Based Skin Anti-Aging Tensioners with Customizable Biofunctions.

Skin anti-aging treatments have become increasingly popular. Currently, the prevalent treatment method involves implanting skin tension regulation threads (skin lifting threads) under the skin, and radiofrequency treatments. In this study, inspired by the natural supercontraction of spider silk, the molecular structure of silk fibroin fibers is modulated into an oriented configuration. This modification endows silk proteins with water-responsive self-contraction capabilities, leading to the development of innovative self-contracting silk-based skin tensioners (SSSTs). To align with clinical requirements, skin tension regulation materials are functionalized by testing for their self-contraction, near-infrared laser heating function, and bacteriostatic properties. The SSSTs exhibited remarkable self-contraction properties, drug-loading and sustained-release capabilities, notable antibacterial effects, controllable degradation, and good biocompatibility. Moreover, the near-infrared light heating function effectively increased subcutaneous temperature, demonstrating its potential for enhancing and prolonging skin lifting effects. Therefore, SSSTs can be applied for skin tension regulation to improve and delay skin aging. The results may pave the way for novel strategies in skin rejuvenation, with broad implications for the field of skin anti-aging.

Ultraflexible PEDOT:PSS/IrOx-Modified Electrodes: Applications in Behavioral Modulation and Neural Signal Recording in Mice.

Recent advancements in neural probe technology have become pivotal in both neuroscience research and the clinical management of neurological disorders. State-of-the-art developments have led to the advent of multichannel, high-density bidirectional neural interfaces that are adept at both recording and modulating neuronal activity within the central nervous system. Despite this progress, extant bidirectional probes designed for simultaneous recording and stimulation are beset with limitations, including elicitation of inflammatory responses and insufficient charge injection capacity. In this paper, we delineate the design and application of an innovative ultraflexible bidirectional neural probe engineered from polyimide. This probe is distinguished by its ability to facilitate high-resolution recordings and precise stimulation control in deep brain regions. Electrodes enhanced with a PEDOT:PSS/IrOx composite exhibit a substantial increase in charge storage capacity, escalating from 0.14 ± 0.01 mC/cm2 to an impressive 24.75 ± 0.18 mC/cm2. This augmentation significantly bolsters the electrodes' charge transfer efficacy. In tandem, we observed a notable reduction in electrode impedance, from 3.47 ± 1.77 MΩ to a mere 41.88 ± 4.04 kΩ, while the phase angle exhibited a positive shift from -72.61 ± 1.84° to -34.17 ± 0.42°. To substantiate the electrodes' functional prowess, we conducted in vivo experiments, where the probes were surgically implanted into the bilateral motor cortex of mice. These experiments involved the synchronous recording and meticulous analysis of neural signal fluctuations during stimulation and an assessment of the probes' proficiency in modulating directional turning behaviors in the subjects. The empirical evidence corroborates that targeted stimulation within the bilateral motor cortex of mice can modulate the intensity of neural signals in the stimulated locale, enabling the directional control of the mice's turning behavior to the contralateral side of the stimulation site.

Tissue/Organ Adaptable Bioelectronic Silk-Based Implants.

Implantable bioelectronic devices, designed for both monitoring and modulating living organisms, require functional and biological adaptability. Pure silk is innovatively employed, which is known for its excellent biocompatibility, to engineer water-triggered, geometrically reconfigurable membranes, on which functions can be integrated by Micro Electro Mechanical System (MEMS) techniques and specially functionalized silk. These devices can undergo programmed shape deformations within 10 min once triggered by water, and thus establishing stable bioelectronic interfaces with natively fitted geometries. As a testament to the applicability of this approach, a twining peripheral nerve electrode is designed, fabricated, and rigorously tested, demonstrating its efficacy in nerve modulation while ensuring biocompatibility for successful implantation.

Advanced nerve regeneration enabled by neural conformal electronic stimulators enhancing mitochondrial transport.

Addressing peripheral nerve defects remains a significant challenge in regenerative neurobiology. Autografts emerged as the gold-standard management, however, are hindered by limited availability and potential neuroma formation. Numerous recent studies report the potential of wireless electronic system for nerve defects repair. Unfortunately, few has met clinical needs for inadequate electrode precision, poor nerve entrapment and insufficient bioactivity of the matrix material. Herein, we present an advanced wireless electrical nerve stimulator, based on water-responsive self-curling silk membrane with excellent bioabsorbable and biocompatible properties. We constructed a unique bilayer structure with an oriented pre-stretched inner layer and a general silk membrane as outer layer. After wetting, the simultaneous contraction of inner layer and expansion of outer layer achieved controllable super-contraction from 2D flat surface to 3D structural reconfiguration. It enables shape-adaptive wrapping to cover around nerves, overcomes the technical obstacle of preparing electrodes on the inner wall of the conduit, and prevents electrode breakage caused by material expansion in water. The use of fork capacitor-like metal interface increases the contact points between the metal and the regenerating nerve, solving the challenge of inefficient and rough electrical stimulation methods in the past. Newly developed electronic stimulator is effective in restoring 10 mm rat sciatic nerve defects comparable to autologous grafts. The underlying mechanism involves that electric stimulation enhances anterograde mitochondrial transport to match energy demands. This newly introduced device thereby demonstrated the potential as a viable and efficacious alternative to autografts for enhancing peripheral nerve repair and functional recovery.

Through-polymer, via technology-enabled, flexible, lightweight, and integrated devices for implantable neural probes.

In implantable electrophysiological recording systems, the headstage typically comprises neural probes that interface with brain tissue and integrated circuit chips for signal processing. While advancements in MEMS and CMOS technology have significantly improved these components, their interconnection still relies on conventional printed circuit boards and sophisticated adapters. This conventional approach adds considerable weight and volume to the package, especially for high channel count systems. To address this issue, we developed a through-polymer via (TPV) method inspired by the through-silicon via (TSV) technique in advanced three-dimensional packaging. This innovation enables the vertical integration of flexible probes, amplifier chips, and PCBs, realizing a flexible, lightweight, and integrated device (FLID). The total weight of the FLIDis only 25% that of its conventional counterparts relying on adapters, which significantly increased the activity levels of animals wearing the FLIDs to nearly match the levels of control animals without implants. Furthermore, by incorporating a platinum-iridium alloy as the top layer material for electrical contact, the FLID realizes exceptional electrical performance, enabling in vivo measurements of both local field potentials and individual neuron action potentials. These findings showcase the potential of FLIDs in scaling up implantable neural recording systems and mark a significant advancement in the field of neurotechnology.

Harmonizing Thickness and Permeability in Bone Tissue Engineering: A Novel Silk Fibroin Membrane Inspired by Spider Silk Dynamics.

Guided bone regeneration gathers significant interest in the realm of bone tissue engineering; however, the interplay between membrane thickness and permeability continues to pose a challenge that can be addressed by the water-collecting mechanism of spider silk, where water droplets efficiently move from smooth filaments to rough conical nodules. Inspired by the natural design of spider silk, an innovative silk fibroin membrane is developed featuring directional fluid transportation via harmoniously integrating a smooth, dense layer with a rough, loose layer; conical microchannels are engineered in the smooth and compact layer. Consequently, double-layered membranes with cone-shaped microporous passageways (CSMP-DSF membrane) are designed for in situ bone repair. Through extensive in vitro testing, it is noted that the CSMP-DSF membrane guides liquid flow from the compact layer's surface to the loose layer, enabling rapid diffusion. Remarkably, the CSMP-DSF membrane demonstrates superior mechanical properties and resistance to bacterial adhesion. When applied in vivo, the CSMP-DSF membrane achieves results on par with the commercial Bio-Gide collagen membranes. This innovative integration of a cross-thickness wetting gradient structure offers a novel solution, harmonizing the often-conflicting requirements of material transport, mechanical strength, and barrier effectiveness, while also addressing issues related to tissue engineering scaffold perfusion.

A mosquito mouthpart-like bionic neural probe.

Advancements in microscale electrode technology have revolutionized the field of neuroscience and clinical applications by offering high temporal and spatial resolution of recording and stimulation. Flexible neural probes, with their mechanical compliance to brain tissue, have been shown to be superior to rigid devices in terms of stability and longevity in chronic recordings. Shuttle devices are commonly used to assist flexible probe implantation; however, the protective membrane of the brain still makes penetration difficult. Hidden damage to brain vessels during implantation is a significant risk. Inspired by the anatomy of the mosquito mouthparts, we present a biomimetic neuroprobe system that integrates high-sensitivity sensors with a high-fidelity multichannel flexible electrode array. This customizable system achieves distributed and minimally invasive implantation across brain regions. Most importantly, the system's nonvisual monitoring capability provides an early warning detection for intracranial soft tissues, such as vessels, reducing the potential for injury during implantation. The neural probe system demonstrates exceptional sensitivity and adaptability to environmental stimuli, as well as outstanding performance in postoperative and chronic recordings. These findings suggest that our biomimetic neural-probe device offers promising potential for future applications in neuroscience and brain-machine interfaces. A mosquito mouthpart-like bionic neural probe consisting of a highly sensitive tactile sensor module, a flexible microelectrode array, and implanted modules that mimic the structure of mosquito mouthparts. The system enables distributed implantation of electrode arrays across multiple brain regions while making the implantation minimally invasive and avoiding additional dural removal. The tactile sensor array can monitor the implantation process to achieve early warning of vascular damage. The excellent postoperative short-term recording performance and long-term neural activity tracking ability demonstrate that the system is a promising tool in the field of brain-computer interfaces.

Spatiotemporal Regulation of Injectable Heterogeneous Silk Gel Scaffolds for Accelerating Guided Vertebral Repair.

Osteoporotic vertebral fracture is jeopardizing the health of the aged population around the world, while the hypoxia microenvironment and oxidative damage of bone defect make it difficult to perform effective tissue regeneration. The balance of oxidative stress and the coupling of vessel and bone ingrowth are critical for bone regeneration. In this study, an injectable heterogeneous silk gel scaffold which can spatiotemporally and sustainedly release bone mesenchymal stem cell-derived small extracellular vesicles, HIF-1α pathway activator, and inhibitor is developed for bone repair and vertebral reinforcement. The initial enhancement of HIF-1α upregulates the expression of VEGF to promote angiogenesis, and the balance of reactive oxygen species level is regulated to effectively eliminate oxidative damage and abnormal microenvironment. The subsequent inhibition of HIF-1α avoids the overexpression of VEGF and vascular overgrowth. Meanwhile, complex macroporous structures and suitable mechanical support can be obtained within the silk gel scaffolds, which will promote in situ bone regeneration. These findings provide a new clinical translation strategy for osteoporotic vertebral augmentation on basis of hypoxia microenvironment improvement.

A Hierarchically Encoded Data Storage Device with Controlled Transiency.

In the era of information explosion, high-security and high-capacity data storage technology attracts more and more attention. Physically transient electronics, a form of electronics that can physically disappear with precisely controlled degradation behaviors, paves the way for secure data storage. Herein, the authors report a silk-based hierarchically encoded data storage device (HEDSD) with controlled transiency. The HEDSD can store electronic, photonic, and optical information simultaneously by synergistically integrating a resistive switching memory (ReRAM), a terahertz metamaterial device, and a diffractive optical element, respectively. These three data storage units have shared materials and structures but diverse encoding mechanisms, which increases the degree of complexity and capacity of stored information. Silk plays an important role as a building material in the HEDSD thanks to its excellent mechanical, optical, and electrical properties and controlled transiency as a naturally extracted protein. By controlling the degradation rate of storage units of the silk-based HEDSD, different degradation modes of the HEDSD, and multilevel information encryption/decryption have been realized. Compared with the conventional memory devices, as-reported silk-based HEDSD can store multilevel complex information and realize multilevel information encryption and decryption, which is highly desirable to fulfill the future demands of secure memory systems and implantable storage devices.

Robotic Manipulation under Harsh Conditions Using Self-Healing Silk-Based Iontronics.

Progress toward intelligent human-robotic interactions requires monitoring sensors that are mechanically flexible, facile to implement, and able to harness recognition capability under harsh environments. Conventional sensing methods have been divided for human-side collection or robot-side feedback and are not designed with these criteria in mind. However, the iontronic polymer is an example of a general method that operates properly on both human skin (commonly known as skin electronics or iontronics) and the machine/robotic surface. Here, a unique iontronic composite (silk protein/glycerol/Ca(II) ion) and supportive molecular mechanism are developed to simultaneously achieve high conductivity (around 6 kΩ at 50 kHz), self-healing (within minutes), strong stretchability (around 1000%), high strain sensitivity and transparency, and universal adhesiveness across a broad working temperature range (-40-120 °C). Those merits facilitate the development of iontronic sensing and the implementation of damage-resilient robotic manipulation. Combined with a machine learning algorithm and specified data collection methods, the system is able to classify 1024 types of human and robot hand gestures under challenging scenarios and to offer excellent object recognition with an accuracy of 99.7%.

Silk Microneedle Patch Capable of On-Demand Multidrug Delivery to the Brain for Glioblastoma Treatment.

Glioblastoma (GBM) is the most common and aggressive primary brain tumor. Surgery followed by chemotherapy and radiotherapy remains the standard treatment strategy for GBM patients. However, challenges still exist when surgery is difficult or impossible to remove the tumor completely. Herein, the design, fabrication and application of a heterogenous silk fibroin microneedle (SMN) patch is reported for circumventing the blood-brain barrier and releasing multiple drugs directly to the tumor site for drug combination treatment. The biocompatible and biodegradable SMN patch can dissolve slowly over time, allowing the sustained release of multiple drugs at different doses. Furthermore, it can be triggered remotely to induce rapid drug delivery at a designated stage after implantation. In the GBM mouse models, two clinically relevant chemotherapeutic agents (thrombin and temozolomide) and targeted drug (bevacizumab) are loaded into the SMN patch with individually controlled release profiles. The drugs are spatiotemporally and sequentially delivered for hemostasis, anti-angiogenesis, and apoptosis of tumor cells. Device application is non-toxic and results in decreased tumor volume and increased survival rate in mice. The SMN patch with on-demand multidrug delivery has potential applications for the combined administration of therapeutic drugs for the clinical treatment of brain tumors when other methods are insufficient.

A silk-based self-adaptive flexible opto-electro neural probe.

The combination of optogenetics and electrophysiological recording enables high-precision bidirectional interactions between neural interfaces and neural circuits, which provides a promising approach for the study of progressive neurophysiological phenomena. Opto-electrophysiological neural probes with sufficient flexibility and biocompatibility are desirable to match the low mechanical stiffness of brain tissue for chronic reliable performance. However, lack of rigidity poses challenges for the accurate implantation of flexible neural probes with less invasiveness. Herein, we report a hybrid probe (Silk-Optrode) consisting of a silk protein optical fiber and multiple flexible microelectrode arrays. The Silk-Optrode can be accurately inserted into the brain and perform synchronized optogenetic stimulation and multichannel recording in freely behaving animals. Silk plays an important role due to its high transparency, excellent biocompatibility, and mechanical controllability. Through the hydration of the silk optical fiber, the Silk-Optrode probe enables itself to actively adapt to the environment after implantation and reduce its own mechanical stiffness to implant into the brain with high fidelity while maintaining mechanical compliance with the surrounding tissue. The probes with 128 recording channels can detect high-yield well-isolated single units while performing intracranial light stimulation with low optical losses, surpassing previous work of a similar type. Two months of post-surgery results suggested that as-reported Silk-Optrode probes exhibit better implant-neural interfaces with less immunoreactive glial responses and tissue lesions. A silk optical fiber-based Silk-Optrode probe consisting of a natural silk optical fiber and a flexible micro/nano electrode array is reported. The multifunctional soft probe can modify its own Young's modulus through hydration to achieve accurate implantation into the brain. The low optical loss and single-unit recording abilities allow simultaneous optogenetic stimulation and multichannel readout, which expands the applications in the operation and parsing of neural circuits in behavioral animals.