Bionic artificial skin with a fully implantable wireless tactile sensory system for wound healing and restoring skin tactile function.

Tactile function is essential for human life as it enables us to recognize texture and respond to external stimuli, including potential threats with sharp objects that may result in punctures or lacerations. Severe skin damage caused by severe burns, skin cancer, chemical accidents, and industrial accidents damage the structure of the skin tissue as well as the nerve system, resulting in permanent tactile sensory dysfunction, which significantly impacts an individual's daily life. Here, we introduce a fully-implantable wireless powered tactile sensory system embedded artificial skin (WTSA), with stable operation, to restore permanently damaged tactile function and promote wound healing for regenerating severely damaged skin. The fabricated WTSA facilitates (i) replacement of severely damaged tactile sensory with broad biocompatibility, (ii) promoting of skin wound healing and regeneration through collagen and fibrin-based artificial skin (CFAS), and (iii) minimization of foreign body reaction via hydrogel coating on neural interface electrodes. Furthermore, the WTSA shows a stable operation as a sensory system as evidenced by the quantitative analysis of leg movement angle and electromyogram (EMG) signals in response to varying intensities of applied pressures.

Ultrasound-Induced Cascade Amplification in a Mechanoluminescent Nanotransducer for Enhanced Sono-Optogenetic Deep Brain Stimulation.

Remote and genetically targeted neuromodulation in the deep brain is important for understanding and treatment of neurological diseases. Ultrasound-triggered mechanoluminescent technology offers a promising approach for achieving remote and genetically targeted brain modulation. However, its application has thus far been limited to shallow brain depths due to challenges related to low sonochemical reaction efficiency and restricted photon yields. Here we report a cascaded mechanoluminescent nanotransducer to achieve efficient light emission upon ultrasound stimulation. As a result, blue light was generated under ultrasound stimulation with a subsecond response latency. Leveraging the high energy transfer efficiency of focused ultrasound in brain tissue and the high sensitivity to ultrasound of these mechanoluminescent nanotransducers, we are able to show efficient photon delivery and activation of ChR2-expressing neurons in both the superficial motor cortex and deep ventral tegmental area after intracranial injection. Our liposome nanotransducers enable minimally invasive deep brain stimulation for behavioral control in animals via a flexible, mechanoluminescent sono-optogenetic system.

Ultrasound programmable hydrogen-bonded organic frameworks for sono-chemogenetics.

The precise control of mechanochemical activation within deep tissues via non-invasive ultrasound holds profound implications for advancing our understanding of fundamental biomedical sciences and revolutionizing disease treatments. However, a theory-guided mechanoresponsive materials system with well-defined ultrasound activation has yet to be explored. Here we present the concept of using porous hydrogen-bonded organic frameworks (HOFs) as toolkits for focused ultrasound programmably triggered drug activation to control specific cellular events in the deep brain, through on-demand scission of the supramolecular interactions. A theoretical model is developed to visualize the mechanochemical scission and ultrasound mechanics, providing valuable guidelines for the rational design of mechanoresponsive materials at the molecular level to achieve programmable and spatiotemporal activation control. To demonstrate the practicality of this approach, we encapsulate designer drug clozapine N-oxide (CNO) into the optimal HOF nanoparticles for FUS gated release to activate engineered G-protein-coupled receptors in the mice and rat ventral tegmental area (VTA), and hence achieved targeted neural circuits modulation even at depth 9 mm with a latency of seconds. This work demonstrates the capability of ultrasound to precisely control molecular interaction and develops ultrasound programmable HOFs to minimally invasive and spatiotemporally control cellular events, thereby facilitating the establishment of precise molecular therapeutic possibilities. We anticipate that this research could serve as a source of inspiration for precise and non-invasive molecular manipulation techniques, potentially applicable in programming molecular robots to achieve sophisticated control over cellular events in deep tissues.

An implantable optogenetic stimulator wirelessly powered by flexible photovoltaics with near-infrared (NIR) light.

Optogenetics is a cutting-edge tool in neuroscience that employs light-sensitive proteins and controlled illumination for neuromodulation. Its main advantage is the ability to demonstrate causal relationships by manipulating the activity of specific neuronal populations and observing behavioral phenotypes. However, the tethering system used to deliver light to optogenetic tools can constrain both natural animal behaviors and experimental design. Here, we present an optically powered and controlled wireless optogenetic system using near-infrared (NIR) light for high transmittance through live tissues. In vivo optogenetic stimulations using this system induced whisker movement in channelrhodopsin-expressing mice, confirming the photovoltaics-generated electrical power was sufficient, and the remote controlling system operated successfully. The proposed optogenetic system provides improved optogenetic applications in freely moving animals.

Active photonic wireless power transfer into live tissues.

Recent advances in soft materials and mechanics activate development of many new types of electrical medical implants. Electronic implants that provide exceptional functions, however, usually require more electrical power, resulting in shorter period of usages although many approaches have been suggested to harvest electrical power in human bodies by resolving the issues related to power density, biocompatibility, tissue damage, and others. Here, we report an active photonic power transfer approach at the level of a full system to secure sustainable electrical power in human bodies. The active photonic power transfer system consists of a pair of the skin-attachable photon source patch and the photovoltaic device array integrated in a flexible medical implant. The skin-attachable patch actively emits photons that can penetrate through live tissues to be captured by the photovoltaic devices in a medical implant. The wireless power transfer system is very simple, e.g., active power transfer in direct current (DC) to DC without extra circuits, and can be used for implantable medical electronics regardless of weather, covering by clothes, in indoor or outdoor at day and night. We demonstrate feasibility of the approach by presenting thermal and mechanical compatibility with soft live tissues while generating enough electrical power in live bodies through in vivo animal experiments. We expect that the results enable long-term use of currently available implants in addition to accelerating emerging types of electrical implants that require higher power to provide diverse convenient diagnostic and therapeutic functions in human bodies.

Robotic Flexible Electronics with Self-Bendable Films.

Mechanical flexibility introduced in functional electronic devices has allowed electronics to avoid mechanical breakage, conform to nonplanar surfaces, or attach to deformable surfaces, leading to greatly expanded applications, and some research efforts have already led to commercialization. However, most of these devices are passively bendable by external driving forces. Actively bendable flexible thin film devices can be applied to new fields with new functionalities. Here, we report robotic flexible electronics with actively self-bendable flexible films that can serve as a platform for flexible electronics and other applications with the capability of reversible bending and unbending by electrical control. Experimental studies along with mechanical modeling enable the predictable and reversible transformation into different structures by adjusting the design parameters. Demonstrations for self-bendable flexible displays and soft robotic hands prove the feasibility of the concept.

Annealing Effects of Parylene-Caulked Polydimethylsiloxane as a Substrate of Electrodes.

This paper investigates the effects of annealing of the electrodes based on parylene-caulked polydimethylsiloxane (pc-PDMS) in terms of mechanical strength and long-term electrical property. Previously, the electrodes based on pc-PDMS showed a better ability to withstand in vivo environments because of the low water absorption and beneficial mechanical properties of the substrate, compared to native PDMS. Moreover, annealing is expected to even strengthen the mechanical strength and lower the water absorption of the pc-PDMS substrate. To characterize the mechanical strength and water absorption of the annealed pc-PDMS, tensile tests were carried out and infrared (IR) spectra were measured using Fourier transform infrared spectroscopy over a month. The results showed that annealed pc-PDMS had higher mechanical strength and lower water absorption than non-annealed pc-PDMS. Then, electrochemical impedance spectroscopy was measured to evaluate the electrical stability of the electrodes based on annealed pc-PDMS in phosphate-buffered saline solution at 36.5 °C. The impedance magnitude of the electrodes on annealed pc-PDMS was twice higher than that of the electrodes on non-annealed pc-PDMS in the initial days, but the impedance magnitude of the electrodes based on two different substrates converged to a similar value after eight months, indicating that the annealing effects disappear after a certain period of time in a physiological environment.

Long-term characterization of neural electrodes based on parylene-caulked polydimethylsiloxane substrate.

This study investigates the mechanical and long-term electrical properties of parylene-caulked polydimethylsiloxane (PDMS) as a substrate for implantable electrodes. The parylene-caulked PDMS is a structure where particles of parylene fill the porous surface of PDMS. This material is expected to have low water absorption and desirable mechanical properties such as flexibility and elasticity that are beneficial in many biomedical applications. To evaluate the mechanical property and electrical stability of parylene-caulked PDMS for potential in-vivo uses, tensile tests were conducted firstly, which results showed that the mechanical strength of parylene-caulked PDMS was comparable to that of native PDMS. Next, surface electrodes based on parylene-caulked PDMS were fabricated and their impedance was measured in phosphate-buffered saline (PBS) solution at 36.5 °C over seven months. The electrodes based on parylene-caulked PDMS exhibited the improved stability in impedance over time than native PDMS. Thus, with improved electrical stability in wet environment and preserved mechanical properties of PDMS, the electrodes based on parylene-caulked PDMS are expected to be suitable for long-term in-vivo applications.

Validation of Computational Studies for Electrical Brain Stimulation With Phantom Head Experiments.

BACKGROUND: Although computational studies of electrical brain stimulation (EBS) have received attention as a cost-effective tool, few studies have validated the technique, particularly in invasive cortical stimulation. OBJECTIVE: In order to validate such studies, we used EBS to compare electric potential distributions generated by both numerical simulations and empirical measurements in three phantom head models (one-/three-layered spherical heads and MRI-based head). METHODS: We constructed spherical phantom heads that consisted of one or three layers, and an anatomical, MRI-based phantom that consisted of three layers and represented the brain or brain/skull/scalp in order to perform both numerical simulations using the finite element method (FEM) and experimental measurements. Two stimulation electrodes (cathode and anode) were implanted in the phantoms to inject regulated input voltage, and the electric potential distributions induced were measured at various points located either on the surface or deep within the phantoms. RESULTS: We observed that both the electric potential distributions from the numerical simulations and experiments behaved similarly and resulted in average relative differences of 5.4% (spherical phantom) and 10.3% (MRI-based phantom). CONCLUSIONS: This study demonstrated that numerical simulation is reasonably consistent with actual experimental measurements; thus, because of its cost-effectiveness, EBS computational studies may be an attractive approach for necessary intensive/extensive studies.