Nanomaterials for Neural Interfaces

This review focuses on the application of nanomaterials for neural interfacing. The junction between nanotechnology and neural tissues can be particularly worthy of scientific attention for several reasons: (i) Neural cells are electroactive, and the electronic properties of nanostructures can be tailored to match the charge transport requirements of electrical cellular interfacing. (ii) The unique mechanical and chemical properties of nanomaterials are critical for integration with neural tissue as long‐term implants. (iii) Solutions to many critical problems in neural biology/medicine are limited by the availability of specialized materials. (iv) Neuronal stimulation is needed for a variety of common and severe health problems. This confluence of need, accumulated expertise, and potential impact on the well‐being of people suggests the potential of nanomaterials to revolutionize the field of neural interfacing. In this review, we begin with foundational topics, such as the current status of neural electrode (NE) technology, the key challenges facing the practical utilization of NEs, and the potential advantages of nanostructures as components of chronic implants. After that the detailed account of toxicology and biocompatibility of nanomaterials in respect to neural tissues is given. Next, we cover a variety of specific applications of nanoengineered devices, including drug delivery, imaging, topographic patterning, electrode design, nanoscale transistors for high‐resolution neural interfacing, and photoactivated interfaces. We also critically evaluate the specific properties of particular nanomaterials—including nanoparticles, nanowires, and carbon nanotubes—that can be taken advantage of in neuroprosthetic devices. The most promising future areas of research and practical device engineering are discussed as a conclusion to the review.     

Design of Architectures and Materials in In‐Plane Micro‐supercapacitors: Current Status and Future Challenges

The rapid development of integrated electronics and the boom in miniaturized and portable devices have increased the demand for miniaturized and on‐chip energy storage units. Currently thin‐film batteries or microsized batteries are commercially available for miniaturized devices. However, they still suffer from several limitations, such as short lifetime, low power density, and complex architecture, which limit their integration. Supercapacitors can surmount all these limitations. Particularly for micro‐supercapacitors with planar architectures, due to their unique design of the in‐plane electrode finger arrays, they possess the merits of easy fabrication and integration into on‐chip miniaturized electronics. Here, the focus is on the different strategies to design electrode finger arrays and the material engineering of in‐plane micro‐supercapacitors. It is expected that the advances in micro‐supercapacitors with in‐plane architectures will offer new opportunities for the miniaturization and integration of energy‐storage units for portable devices and on‐chip electronics.     

Biohybrid Design Gets Personal: New Materials for Patient-Specific Therapy

Precision medicine requires materials and devices that can sense and adapt to dynamic physiological and pathological conditions. This motivates the design and manufacture of biohybrid materials that mimic the responsive behaviors demonstrated by natural biological systems. Two parallel approaches to biohybrid design are presented—biomimetics and biointegration. Biohybrid hydrogels that mimic the form and function of natural materials, or that integrate living cells or bioactive moieties, can respond to a range of environmental stimuli in parallel, including heat, light, pH, hydration, enzymes, and electric, mechanical, and magnetic forces. A range of examples that illustrate the tremendous potential of this nascent discipline are presented, and ongoing technical challenges related to manufacturing, storage, transport, and external noninvasive control of these materials that will need to be overcome in the coming years are outlined. The ethical, educational, and regulatory challenges that will govern translation of biohybrid design into medical applications are also discussed. Personalized medical therapies that target the precise needs of patients are a critically needed and expanding market. Biohybrid design offers the unique ability to manufacture materials and devices that match the dynamic and patient-specific in vivo environment, promising to generate more effective and safe therapies that enable personalized care.     

Highly Stretchable,Compliant, Polymeric Microelectrode Arrays for In Vivo Electrophysiological Interfacing

Polymeric microelectrode arrays (MEAs) are emerging as a new generation of biointegrated microelectrodes to transduce original electrochemical signals in living tissues to external electrical circuits, and vice versa. So far, the challenge of stretchable polymeric MEAs lies in the competition between high stretchability and good electrode–substrate adhesion. The larger the stretchability, the easier the delamination of electrodes from the substrate due to the mismatch in their Young's modulus. In this work, polypyrrole (PPy) electrode materials are designed, with PPy nanowires integrated on the high conductive PPy electrode arrays. By utilizing this electrode material, for the first time, stretchable polymeric MEAs are fabricated with both high stretchability (≈100%) and good electrode–substrate adhesion (1.9 MPa). In addition, low Young's modulus (450 kPa), excellent recycling stability (10 000 cycles of stretch), and high conductivity of the MEAs are also achieved. As a proof of concept, the as‐prepared polymeric MEAs are successfully used for conformally recording the electrocorticograph signals from rats in normal and epileptic states, respectively. Further, these polymeric MEAs are also successful in stimulating the ischiadic nerve of the rat. This strategy provides a new perspective to the highly stretchable and mechanically stable polymeric MEAs, which are vital for compliant neural electrodes.     

Perspektiven der Plasmamedizin

Prospects of plasma medicine: Applications of Tissue Tolerable Plasmas (TTP) Based on the current knowledge on the physical properties and biological effects of tissue tolerable plasma (ttp) potential perspectives of plasma medicine are discussed. Currently, the foundations for the following medical applications of ttp are developed by an interdisciplinary research team: Prevention and/or treatment of diseases such as chronic wounds, skin and mucosal infectious diseases, localized tumors, promotion of angiogenesis, and tissue ablation Inhibition and/or elimination of biofilms by prevention of biofilm development due to surface treatment and/or plasma steered application of antimicrobial active layers with drug delivery function on foreign objects implanted into humans (implantable prosthesis, contact lenses, stents etc.) as well as elimination of biofilms by direct action of ttp on surfaces and tissues (chronic wounds, tooth surface, prosthesis) promotion of the incorporation of implants into viable tissue by changing the surface of materials (hydrophobicity) Promotion of penetration of topically applied drugs with therapeutic results Assessment of veterinary indications Improved cleaning performance in reprocessing of medical devices by surface modification.     

Interfacing Photosynthetic Membrane Protein with Mesoporous WO3 Photoelectrode for Solar Water Oxidation

Photosynthetic biocatalysts are emerging as a new class of materials, with their sophisticated and intricate structure, which promise improved remarkable quantum efficiency compared to conventional inorganic materials in artificial photosynthesis. To break the limitation of efficiency, the construction of bioconjugated photo‐electrochemical conversion devices has garnered substantial interest and stood at the frontier of the multidisciplinary research between biology and chemistry. Herein, a biohybrid photoanode of a photosynthetic membrane protein (Photosystem II (PS II)), extracted from fresh spinach entrapped on mesoporous WO₃ film, is fabricated on fluorine‐doped tin oxide. The PS II membrane proteins are observed to communicate with the WO₃ electrode in the absence of any soluble redox mediators and sacrificial reagents under the visible light of the solar spectrum, even to 700 nm. The biohybrid electrode undergoes electron transfer and generates a significantly enhanced photocurrent compared to previously reported PS II‐based photoanodes with carbon nanostructures or other semiconductor substrates for solar water oxidation. The maximum incident photon‐to‐current conversion efficiency reaches 15.24% at 400 nm in the visible light region. This work provides some insights and possibilities into the efficient assembly of a future solar energy conversion system based on visible‐light‐responsive semiconductors and photosynthetic proteins.     

Comparison of the tissue reaction to implants made of a beta titanium alloy and pure titanium. Experimental study on rabbits

Commercially pure titanium (Ti cp) has been used successfully as an implant material in fracture fixation devices for many years. Ti cp is comparatively soft, but the mechanical properties, such as strength and ductility, can be adjusted by different means over a wide range. Titanium changes its crystal structure from a hexagonal (alpha) phase to the cubic (beta) phase at about 882 °C. Cubic titanium has the advantage of being very malleable (ductile), but in order to stabilize it at room temperature, additions of suitable alloying elements are required. In this study the soft tissue reaction to implants made from a beta titanium alloy (Ti–Mo–Zr–Al) with four different surface treatments is evaluated. The results are compared to Ti cp implants having the same surface conditions, and to electropolished stainless steel plates as controls. A minimum of four small plates of each group were implanted in rabbit tibiae for 3 months. Histomorphometric results show that the thickness of the soft tissue reaction layer, and the number of blood vessels, connective tissue cells (fibroblasts, fibrocytes), lymphocytes, and foreign body giant cells are not significantly different between beta titanium and Ti cp plates. For stainless steel plates the soft tissue reaction layer is thicker, and the numbers of macrophages and connective tissue cells are higher. Excellent biocompatibility was observed for this beta titanium alloy. The mechanical properties of this alloy surpass those of Ti cp, and because of the good tissue tolerance, this material seems to be advantageous and should enter into clinical testing.     

Do ‘passive’ medical titanium surfaces deteriorate in service in the absence of wear?

Globally, more than 1000 tonnes of titanium (Ti) is implanted into patients in the form of biomedical devices on an annual basis. Ti is perceived to be ‘biocompatible’ owing to the presence of a robust passive oxide film (approx. 4 nm thick) at the metal surface. However, surface deterioration can lead to the release of Ti ions, and particles can arise as the result of wear and/or corrosion processes. This surface deterioration can result in peri-implant inflammation, leading to the premature loss of the implanted device or the requirement for surgical revision. Soft tissues surrounding commercially pure cranial anchorage devices (bone-anchored hearing aid) were investigated using synchrotron X-ray micro-fluorescence spectroscopy and X-ray absorption near edge structure. Here, we present the first experimental evidence that minimal load-bearing Ti implants, which are not subjected to macroscopic wear processes, can release Ti debris into the surrounding soft tissue. As such debris has been shown to be pro-inflammatory, we propose that such distributions of Ti are likely to effect to the service life of the device.     

有机太阳能电池ITO电极的光刻制备法及其研究

目前有机太阳能电池是光电行业研究的热点之一。通常该器件以ITO为阳极，通过真空蒸镀的方法制作。在对器件进行测试时，ITO电极的设计制作，有利于器件的保护。用光刻技术进行ITO电极的制作，可以得到非常精细的结果。重点阐述了利用光刻方法制作优良ITO电极的注意点，包括表面清洗、曝光控制、显影控制和腐蚀工艺，其中由于不同ITO玻璃的导电层厚度、各成分含量不同，所以腐蚀工艺的研究是重点中的重点。提供了对生成光刻ITO电极的质量进行准确评价的一种简便方法。     

Material design of bioabsorbable inorganic/organic composites for bone regeneration

Two new bioabsorbable inorganic/organic composite materials were developed for bone regeneration. One material used was beta-TCP/PLGC in which poly(L-lactide-co-glycolide-co-epsilon-caprolactone) and beta-tricalcium phosphate were used as the matrix and filler, respectively. The other material used was HAp/Col-a soft nanocomposite of hydroxyapatite and type I collagen. Using these composites, two bone implants were designed. The efficacy of these implants was investigated by applying them to the critical-sized bone defects that were created in the canine tibia. Although no tissue engineering techniques such as application of growth factors or stem cells was utilized, successful healing was observed. These results suggested that bone regeneration in the critical-sized defects is possible without the use of growth factors or stem cells if the materials and the bone implants are suitably designed.     

Mass customization of medical devices and implants: state of the art and future directions

The medical field is one in which the need for customization can be clear cut, as providing tailored devices and implants for unique physiologies can provide for a better overall treatment than the use of 'off the shelf' devices and implants. Customization in the production of medical products can be roughly divided into consideration of medical devices, and of implantable parts or systems. The present paper outlines the current state of the art in both of these areas, presents details of projects that are ongoing at the University of Leeds and outlines future research directions.     

Mass customization of medical devices and implants: state of the art and future directions

The medical field is one in which the need for customization can be clear cut, as providing tailored devices and implants for unique physiologies can provide for a better overall treatment than the use of ‘off the shelf’ devices and implants. Customization in the production of medical products can be roughly divided into consideration of medical devices, and of implantable parts or systems. The present paper outlines the current state of the art in both of these areas, presents details of projects that are ongoing at the University of Leeds and outlines future research directions.     

A percutaneous device as model to study the in vivo performance of implantable amperometric glucose sensors

Glucose kinetics were investigated in subcutaneous tissue of rabbits, in which a percutaneous device was implanted. The device was used for collection of tissue fluid and as carrier of an amperometric glucose sensor. Changes in glycaemia were reflected in subcutaneous tissue fluid. However, a limited number of responses of the implanted sensors were observed. Histologic evaluation showed thin fibrous capsules surrounding the implants. Accumulations of inflammatory cells were observed inside the subcutaneous chamber. The experiments again showed that changes in blood glucose concentration can be measured in subcutaneous tissue fluid collected with a percutaneous device. Nevertheless, implanted glucose sensors could not reliably monitor these changes. Supported by our histological observations and sufficient in vitro performance, we suppose that the cellular reaction to the sensor plays an important role in this poor in vivo performance. In combination with adsorption of tissue fluid proteins, this results in a reversible deactivation of implanted sensors. The exact mechanisms involved in this process are currently unknown and need further investigation.     

Piezoelectric contrast materials for ultrasound imaging

Piezoelectric ceramics and polymers can be used as a type of marker and contrast material for medical ultrasound imaging systems. High-frequency electrical signals are detected from surface electrodes when these materials are introduced into conducting media such as tissue and scanned by ultrasound imaging systems. Detected signals are applied to the imaging circuits of a modified ultrasound system such that they display a unique type of electrical image that shows the piezomaterial's polarization, shape, and position at arbitrarily high contrast compared to the conventional ultrasound acoustic image. The resulting piezoelectric image can be merged in real-time with conventional ultrasound acoustic imaging to form a composite image. This approach is of interest in the development of improved techniques for imaging medical devices that are implanted or otherwise introduced into the body.     

Suspended nanoporous membranes as interfaces for neuronal biohybrid systems

A biohybrid system composed of neuronal cells and silicon-supported nanoporous membranes has been designed to facilitate control of the biochemical environment of neuronal networks with cellular resolution. The membranes may exhibit variable pore sizes and interpore distances and are interfaced to a microfluidic device. Different porosity parameters give rise to changes in the transconductance of the nanopores and can therefore be used to control diffusion of molecules through the membranes. It was shown that the porous membranes are biocompatible with primary vertebrate as well as insect neurons. Our results indicate that nanoporous membranes may be used to interface with biological materials in a biohybrid system, for example as an artificial chemical synapse interface.     

Hydroprinted Liquid‐Alloy‐Based Morphing Electronics for Fast‐Growing/Tender Plants: From Physiology Monitoring to Habit Manipulation

Monitoring physiological signals and manipulating growth habits of living plants in real time are important for botany research, biohybrid plant robots, and precision agriculture. Although emerging epidermal electronics that can conveniently acquire vital signals of living organisms exhibit a high potential for such scenarios, it is a significant challenge to adapt such devices for plants, because they are fragile and usually have complex surfaces that can change significantly during rapid growth. A gentle fabrication process is critical in order to employ compliant electronic systems to adapt to this highly dynamic situation. In this study, a hydroprinted liquid‐alloy‐based morphing electronics (LAME) process is employed for fast‐growing plants that will sense physiological signals and even function as a biohybrid to determine plant behavior on demand. Besides various surfaces of inorganic targeting substrates, pinning liquid alloy circuits onto the complex plant epidermis is enhanced by introducing high‐surface‐energy liquid. Functionally, the new developed LAME can be used to monitor leaf moisture content and length, and manipulate leaf and bean sprout orientation. This study lays the foundation for a new form of morphing electronics for botany or biohybrid plant robots, potentially impacting the next generation of precision agriculture and smart hybrid robots.     

Recent Advances in Materials,Devices, and Systems for Neural Interfaces

Technologies capable of establishing intimate, long‐lived optical/electrical interfaces to neural systems will play critical roles in neuroscience research and in the development of nonpharmacological treatments for neurological disorders. The development of high‐density interfaces to 3D populations of neurons across entire tissue systems in living animals, including human subjects, represents a grand challenge for the field, where advanced biocompatible materials and engineered structures for electrodes and light emitters will be essential. This review summarizes recent progress in these directions, with an emphasis on the most promising demonstrated concepts, materials, devices, and systems. The article begins with an overview of electrode materials with enhanced electrical and/or mechanical performance, in forms ranging from planar films, to micro/nanostructured surfaces, to 3D porous frameworks and soft composites. Subsequent sections highlight integration with active materials and components for multiplexed addressing, local amplification, wireless data transmission, and power harvesting, with multimodal operation in soft, shape‐conformal systems. These advances establish the foundations for scalable architectures in optical/electrical neural interfaces of the future, where a blurring of the lines between biotic and abiotic systems will catalyze profound progress in neuroscience research and in human health/well‐being.     

The Future of Neuroimplantable Devices: A Materials Science and Regulatory Perspective

The past two decades have seen unprecedented progress in the development of novel materials, form factors, and functionalities in neuroimplantable technologies, including electrocorticography (ECoG) systems, multielectrode arrays (MEAs), Stentrode, and deep brain probes. The key considerations for the development of such devices intended for acute implantation and chronic use, from the perspective of biocompatible hybrid materials incorporation, conformable device design, implantation procedures, and mechanical and biological risk factors, are highlighted. These topics are connected with the role that the U.S. Food and Drug Administration (FDA) plays in its regulation of neuroimplantable technologies based on the above parameters. Existing neuroimplantable devices and efforts to improve their materials and implantation protocols are first discussed in detail. The effects of device implantation with regards to biocompatibility and brain heterogeneity are then explored. Topics examined include brain-specific risk factors, such as bacterial infection, tissue scarring, inflammation, and vasculature damage, as well as efforts to manage these dangers through emerging hybrid, bioelectronic device architectures. The current challenges of gaining clinical approval by the FDA—in particular, with regards to biological, mechanical, and materials risk factors—are summarized. The available regulatory pathways to accelerate next-generation neuroimplantable devices to market are then discussed.     

Emerging Semitransparent Solar Cells: Materials and Device Design

Semitransparent solar cells can provide not only efficient power‐generation but also appealing images and show promising applications in building integrated photovoltaics, wearable electronics, photovoltaic vehicles and so forth in the future. Such devices have been successfully realized by incorporating transparent electrodes in new generation low‐cost solar cells, including organic solar cells (OSCs), dye‐sensitized solar cells (DSCs) and organometal halide perovskite solar cells (PSCs). In this review, the advances in the preparation of semitransparent OSCs, DSCs, and PSCs are summarized, focusing on the top transparent electrode materials and device designs, which are all crucial to the performance of these devices. Techniques for optimizing the efficiency, color and transparency of the devices are addressed in detail. Finally, a summary of the research field and an outlook into the future development in this area are provided.     

Designing porous scaffolds for tissue engineering

Biomaterials are either modified natural or synthetic materials, with an appropriate response in the host tissue, which find application in a wide spectrum of implants and prostheses used in reconstructive medicine. The subsequent integration and longevity of the implanted device depends on the effectiveness of the associated biological repair. Hence, there has been considerable interest in the development of novel, second generation, biomaterials, which are favourably bioactive in terms of promoting the desired cellular response in vivo. Such biomaterials in a porous form can also act as cellular scaffolds and allow in vitro, as well as in vivo incorporation of the appropriate tissue cells, with potential control of the sequence of cell attachment, proliferation and the production of extra-cellular matrix. Such generic tissue engineering depends critically on the porous architecture of the biomaterial scaffold so as to allow both the cellular ingress and vascularization required to create a living tissue. The particular requirements of tissue-engineering scaffolds with respect to macro- and micro-porosity, as well as chemistry, are reviewed.