Recent Advances in Transistor‐Based Artificial Synapses

Simulating biological synapses with electronic devices is a re‐emerging field of research. It is widely recognized as the first step in hardware building brain‐like computers and artificial intelligent systems. Thus far, different types of electronic devices have been proposed to mimic synaptic functions. Among them, transistor‐based artificial synapses have the advantages of good stability, relatively controllable testing parameters, clear operation mechanism, and can be constructed from a variety of materials. In addition, they can perform concurrent learning, in which synaptic weight update can be performed without interrupting the signal transmission process. Synergistic control of one device can also be implemented in a transistor‐based artificial synapse, which opens up the possibility of developing robust neuron networks with significantly fewer neural elements. These unique features of transistor‐based artificial synapses make them more suitable for emulating synaptic functions than other types of devices. However, the development of transistor‐based artificial synapses is still in its very early stages. Herein, this article presents a review of recent advances in transistor‐based artificial synapses in order to give a guideline for future implementation of synaptic functions with transistors. The main challenges and research directions of transistor‐based artificial synapses are also presented.     

Multicompartment Polymer Vesicles with Artificial Organelles for Signal‐Triggered Cascade Reactions Including Cytoskeleton Formation

Organelles, i.e., internal subcompartments of cells, are fundamental to spatially separate cellular processes, while controlled intercompartment communication is essential for signal transduction. Furthermore, dynamic remodeling of the cytoskeleton provides the mechanical basis for cell shape transformations and mobility. In a quest to develop cell‐like smart synthetic materials, exhibiting functional flexibility, a self‐assembled vesicular multicompartment system, comprised of a polymeric membrane (giant unilamellar vesicle, GUV) enveloping polymeric artificial organelles (vesicles, nanoparticles), is herein presented. Such multicompartment assemblies respond to an external stimulus that is transduced through a precise sequence. Stimuli‐triggered communication between two types of internal artificial organelles induces and localizes an enzymatic reaction and allows ion‐channel mediated release from storage vacuoles. Moreover, cytoskeleton formation in the GUVs' lumen can be triggered by addition of ionophores and ions. An additional level of control is achieved by signal‐triggered ionophore translocation from organelles to the outer membrane, triggering cytoskeleton formation. This system is further used to study the diffusion of various cytoskeletal drugs across the synthetic outer membrane, demonstrating potential applicability, e.g., anticancer drug screening. Such multicompartment assemblies represent a robust system harboring many different functionalities and are a considerable leap in the application of cell logics to reactive and smart synthetic materials.     

Controllable Stiffness Origami “Skeletons” for Lightweight and Multifunctional Artificial Muscles

Flexible, material‐based, artificial muscles enable compliant and safe technologies for human–machine interaction devices and adaptive soft robots, yet there remain long‐term challenges in the development of artificial muscles capable of mimicking flexible, controllable, and multifunctional human activity. Inspired by human limb's activity strategy, combining muscles' adjustable stiffness and joints' origami folding, controllable stiffness origami “skeletons,” which are created by laminar jamming and origami folding of multiple layers of flexible sandpaper, are embedded into a common monofunctional vacuumed‐powered cube‐shaped (CUBE) artificial muscle, thereby enabling the monofunctional CUBE artificial muscle to achieve lightweight and multifunctionality as well as controllable force/motion output without sacrificing its volume and shape. Successful demonstrations of arms self‐assembly and cooperatively gripping different objects and a “caterpillar” robot climbing different pipes illustrate high operational redundancy and high‐force output through “building blocks” assembly of multifunctional CUBE artificial muscles. Controllable stiffness origami “skeletons” offer a facile and low‐cost strategy to fabricate lightweight and multifunctional artificial muscles for numerous potential applications such as wearable assistant devices, miniature surgical instruments, and soft robots.     

Biocatalytic Metal‐Organic Framework‐Based Artificial Cells

Artificial cells or cell mimics have drawn significant attention in cell biology and material science in the last decade and its development will provide a powerful toolbox for studying the origin of life and pave the way for novel biomedical applications. Artificial cells and their subcompartments are typically constructed from a semipermeable membrane composed of liposomes, polymersomes, hydrogels, or simply aqueous droplets enclosing bioactive molecules to perform cellular‐mimicking activities such as compartmentalization, communication, metabolism, or reproduction. Despite the rapid progress, concerns regarding their physical stability (e.g., thermal or mechanical) and tunability in membrane permeability have significantly hindered artificial cells systems in real‐life applications. In addition, developing a facile and versatile system that can mimic multiple cellular tasks is advantageous. Here, an ultrastable, multifunctional and stimulus‐responsive artificial cell system is reported. Constructed from metal‐phenolic network membranes enclosing enzyme‐containing metal‐organic frameworks as organelles, the bionic cell system can mimic multiple cellular tasks including molecular transport regulation, cell metabolism, communication and programmed degradation, and significantly extends its stability range across various chemical and physical conditions. It is believed that the development of such responsive cell mimics will have significant potentials for studying cellular reactions and have future applications in biosensing and drug delivery.     

Recent Advances in Microfluidic Technologies for the Construction of Artificial Cells

Artificial cells are synthetic constructs that emulate natural cells, with potential applications in areas of energy science, environmental treatment, and the study of life's origins. Nevertheless, the construction of artificial cells is a formidable undertaking, given the intricate nature of natural cells in structures, functions, and working mechanisms. With precise control, high automation, and excellent uniformity, microfluidics has emerged as a promising approach for the construction of artificial cells. This review summarizes the latest microfluidic techniques utilized to construct artificial cells, ranging from simple droplets to sophisticated cell-inspired systems. These include the generation of droplets, the production of vesicles (lipid-based and polymer-based vesicles), the fabrication of polymeric microparticles with various compartments, shapes, and microstructures, as well as the manufacture of sophisticated cell-inspired systems. The characteristics of different methods for the construction of artificial cells are discussed in detail. Furthermore, the wide-ranging applications of artificial cells are also showcased. Finally, contemporary obstacles and forthcoming advancements are discussed in the field of microfluidic-based artificial cells. This review is supposed to stimulate research in the construction of more functional and natural-like artificial cells, as well as works in the fields of material, biology, environment, medicine, and energy.     

Living Cell-Derived Intelligent Nanobots for Precision Oncotherapy

The progress of precision oncology medicine is always limited by the tumor off-targeting, the drug side effects, and the treatment inefficiency due to the complex and ever-changing tumor microenvironment. Living cells, such as blood cells and immune cells, exhibit natural tumor tropism, controllable physicochemical modification, and excellent biocompatibility, which provide an advantageous pathway for innovative and efficient tumor suppression. Armed with nanoengineering techniques, artificial living cells harness their inherent biological properties to precisely identify and eradicate tumors, demonstrating broad biological application prospects and great transformational potential in personalized cancer therapy. Here, the recent advances of living cell-based bionanobots including platelets, red blood cells, neutrophil, macrophage, and CAR-T cells for cancer precision therapy and immune regulation are summarized, and the efficient anti-tumor strategies for engineering living cell nanorobots to overcome complex biological barriers and immune suppression are also outlined (e.g., immunotherapy, sonodynamic therapy, chemo/radiotherapy, and phototherapy). In addition, the study discusses the advantages, limitations, and current challenges of artificial living cell-based drug delivery systems, and provide perspectives on the future development of living cell-mediated precision tumor nanomedicine.     

Lessons Learned from Engineering Biologically Active Hybrid Nano/Micro Devices

Engineering devices based upon the interfacing of biological with inorganic systems have led to fascinating research results and present important implications for next‐generation technologies. The development of cell‐ and protein‐based micro/nano systems has demonstrated that several key factors must be considered when establishing fabrication rules. These include material interface properties, preserving biological viability, as well as self‐assembly as a device‐fabrication methodology, to name a few. Here, we present two proposed devices that have been developed through the application of these principles. They include muscle‐powered microfabricated devices, as well as protein‐functionalized polymeric vesicles based on protein‐coupling reactions. These systems have successfully bridged the gap between biological and conventional engineering to yield exciting prospects, as well as important lessons and questions for the development of cell‐/protein‐based hybrids.     

Self‐Assembled Heteroepitaxial Oxide Nanocomposite Thin Film Structures: Designing Interface‐Induced Functionality in Electronic Materials

Achieving self‐assembling/self‐organizing systems is the holy grail of nanotechnology. Spontaneous organization is not unique to the physical sciences since nature has been producing such systems for millions of years. In biological systems global patterns emerge from numerous interactions among lower‐level components of the system. The same is true for physical systems. In this review, the self‐assembly mechanisms of oxide nanocomposite films, as well as the advantageous functionalities that arise from such ordered structures, are explored.     

Structural and Functional Adaptive Artificial Bone: Materials,Fabrications, and Properties

It is an urgent need that defect repair can develop from simple device fixation to living tissue reconstruction, from short life function replacement to permanent regeneration repair. At present, bone transplantation has become the second largest transplantation surgery after blood transfusion, and artificial bone transplantation generates great hope for the repair and treatment of bone defect. In order to repair bone defect, artificial bone must have good biological properties and sufficient mechanical properties, and it should also have the shape matching to bone defect site and the connected porous structure. For structures and properties requirements of artificial bone, in this review three major challenges faced by artificial bone transplantation are systemtically analyzed and current methods and strategies to address these issues are discussed: 1) the need for developing a type of bone scaffold material with both biological and mechanical properties, 2) the need for realizing the controllable fabrication of individual shape and multistage pore structure of bone scaffold, 3) the need for realizing the transformation from man-made structure to biological structure. Besides, it summarizes the advantages and disadvantages of these methods and discusses the potential future directions of structural and functional adaptive artificial bone for bone defect regeneration.     

Improvement of Biological Organisms Using Functional Material Shells

Biomineralization brings inorganic materials into biological organisms and it plays an important role in natural evolution. Inspired by biomineralized eggs and diatoms with protective shell structures, scientists have artificially endowed organisms with functional materials. The resulting organism–material hybrids become more robust and even evolve new functions. This feature article reviews recent achievements of organism improvements by various material shells and related applications in cell protection, storage, thermal stability, biological stealth, photosynthesis and biocatalysis, etc. Different from the previous understanding of biomineralization, the regulation effects of materials on organism functions are highlighted in these biomineralization‐inspired biological improvements, which present an artificial evolution strategy by using material techniques. We suggest that rationally designed organism–materials with optimized functions can shed light on solving global problems such as energy crisis and environmental pollution, as well as on improving medical treatment and intricate material designing. More generally, the studies of material‐based organism improvement can combine biological and material sciences together for a closer integration.     

Two‐Step Sequential Deposition of Organometal Halide Perovskite for Photovoltaic Application

Organometal halide perovskite materials have become a superstar in the photovoltaic (PV) field because of their advantageous properties, which boost the power conversion efficiency (PCE) of perovskite solar cells (PSCs) from about 3.8% to above 22% in just seven years. Most importantly, such promising achievement is mainly based on its low‐cost and solution‐processed fabrication technique. One of the most promising and famous approaches to fabricating perovskite is a two‐step sequential deposition method because precursor (e.g., PbI₂) deposition is controllable, versatile, and flexible. Due to tremendous efforts, great progress has been achieved on the two‐step sequential deposition method, which helps to promote the development of PSCs. Herein, the progresses on the two‐step sequential deposition method of perovskite layers is reviewed thoroughly. At first, the reaction process and principle is introduced and discussed. Then, the research on the deposition techniques, structures, and compositions of precursors (the first step) is presented. Subsequently, the developments on the conversion techniques, conversion solutions, and growth of large crystals at the second step are introduced. Finally, four important issues on the two‐step sequential deposition method will be stated, accompanied with proposed solutions.     

Using SERS Tags to Image the Three‐Dimensional Structure of Complex Cell Models

Methods to image complex 3D cell cultures are limited by issues such as fluorophore photobleaching and decomposition, poor excitation light penetration, and lack of complementary techniques to verify the 3D structure. Although it remains insufficiently demonstrated, surface‐enhanced Raman scattering (SERS) imaging is a promising tool for the characterization of biological complex systems. To this aim, a controllable 3D cell culture model which spans nearly 1 cm² in surface footprint is designed. This structure is composed of fibroblasts containing SERS‐encoded nanoparticles (i.e., SERS tags), arranged in an alternating layered structure. This “sandwich” type structure allows monitoring of the SERS signals in the z‐axis and with mm dimensions in the xy‐axis. Taking advantage of correlative microscopy techniques such as electron microscopy, it is possible to corroborate nanoparticle positioning and distances in z‐depths of up to 150 µm. This study reveals a proof‐of‐concept method for detailed 3D SERS imaging of a complex, dense 3D cell culture model.     

MaRMI‐III: A Methodology for Component‐Based Development

As component‐based development (CBD) rapidly spread throughout the software industry, a comprehensive methodology is needed to apply it more systematically. For this purpose, a new CBD methodology named Magic & Robust Methodology Integrated III (MaRMI‐III) has been developed. The purpose of this paper is to present MaRMI‐III by its constituent processes and claim that it can be used to support system developers conduct CBD in a consistent manner. First, we review the CBD approach to system development and the role of CBD methodology, and then we explain the several characteristics of MaRMI‐III which are considered necessary to the CBD environment. Next, we explain a process model of MaRMI‐III which separates the development process from the project management process and prescribes well‐ordered activities and tasks that the developer should conduct. Each phase forming the Process Model is explained in terms of its objectives and main constituent activities. Some techniques and workproducts related to each phase are also explained. Finally, to examine the usefulness of MaRMI‐III, an analytical comparison with other CBD methodologies and the results of a questionnaire survey are described.     

Formation of Embryoid Bodies with Controlled Sizes and Maintained Pluripotency in Three‐Dimensional Inverse Opal Scaffolds

Embryoid bodies (EBs) are aggregates of cells derived from embryonic stem (ES) cells, which can serve as a good model system to investigate molecular and cellular interactions in the earliest stages of embryo development. Current methods for producing EBs mainly rely on the use of hanging drops or suspensions in non‐tissue culture treated plates, microwells, and spinner flasks. The capability of these methods is limited in terms of size uniformity and distribution as well as scalability. Here, a new platform based on three‐dimensional alginate inverse opal scaffolds with uniform pores is presented, where uniform EBs with controllable sizes could be produced in the pores and then recovered after disintegration of the scaffolds. The size of the EBs could be readily controlled by varying the culture time and/or by using scaffolds with different pore sizes. The EBs maintained their viability and undifferentiated state, and they were able to differentiate into specific lineages upon stimulation.     

Living Yeast Cells as a Controllable Biosynthesizer for Fluorescent Quantum Dots

There are currently some problems in the field of chemical synthesis, such as environmental impact, energy loss, and safety, that need to be tackled urgently. An interdisciplinary approach, based on different backgrounds, may succeed in solving these problems. Organisms can be chosen as potential platforms for materials fabrication, since biosystems are natural and highly efficient. Here, an example of how to solve some of these chemical problems through biology, namely, through a novel biological strategy of coupling intracellular irrelated biochemical reactions for controllable synthesis of multicolor CdSe quantum dots (QDs) using living yeast cells as a biosynthesizer, is demonstrated. The unique fluorescence properties of CdSe QDs can be utilized to directly and visually judge the biosynthesis phase to fully demonstrate this strategy. By such a method, CdSe QDs, emitting at a variety of single fluorescence wavelengths, can be intracellularly, controllably synthesized at just 30°C instead of at 300°C with combustible, explosive, and toxic organic reagents. This green biosynthetic route is a novel strategy of coupling, with biochemical reactions taking place irrelatedly, both in time and space. It involves a remarkable decrease in reaction temperature, from around 300 °C to 30 °C and excellent color controllability of CdSe photoluminescence. It is well known that to control the size of nanocrystals is a mojor challenge in the biosynthesis of high‐quality nanomaterials. The present work demonstrates clearly that biological systems can be creatively utilized to realize controllable unnatural biosynthesis that normally does not exist, offering new insights for sustainable chemistry.     

Dopamine: Just the Right Medicine for Membranes

Mussel‐inspired chemistry has attracted widespread interest in membrane science and technology. Demonstrating the rapid growth of this field over the past several years, substantial progress has been achieved in both mussel‐inspired chemistry and membrane surface engineering based on mussel‐inspired coatings. At this stage, it is valuable to summarize the most recent and distinctive developments, as well as to frame the challenges and opportunities remaining in this field. In this review, recent advances in rapid and controllable deposition of mussel‐inspired coatings, dopamine‐assisted codeposition technology, and photoinitiated grafting directly on mussel‐inspired coatings are presented. Some of these technologies have not yet been employed directly in membrane science. Beyond discussing advances in conventional membrane processes, emerging applications of mussel‐inspired coatings in membranes are discussed, including as a skin layer in nanofiltration, interlayer in metal‐organic framework based membranes, hydrophilic layer in Janus membranes, and protective layer in catalytic membranes. Finally, some critical unsolved challenges are raised in this field and some potential pathways are proposed to address them.     

Ionic Tactile Sensors for Emerging Human‐Interactive Technologies: A Review of Recent Progress

Ionic tactile sensors (ITS) represent a new class of deformable sensory platforms that mimic not only the tactile functions and topological structures but also the mechanotransduction mechanism across the biological ion channels in human skin, which can demonstrate a more advanced biological interface for targeting emerging human‐interactive technologies compared to conventional e‐skin devices. Recently, flexible and even stretchable ITS have been developed using novel structural designs and strategies in materials and devices. These skin‐like tactile sensors can effectively sense pressure, strain, shear, torsion, and other external stimuli with high sensitivity, high reliability, and rapid response beyond those of human perception. In this review, the recent developments of the ITS based on the novel concepts, structural designs, and strategies in materials innovation are entirely highlighted. In particular, biomimetic approaches have led to the development of the ITS that extend beyond the tactile sensory capabilities of human skin such as sensitivity, pressure detection range, and multimodality. Furthermore, the recent progress in self‐powered and self‐healable ITS, which should be strongly required to allow human‐interactive artificial sensory platforms is reviewed. The applications of ITS in human‐interactive technologies including artificial skin, wearable medical devices, and user‐interactive interfaces are highlighted. Last, perspectives on the current challenges and the future directions of this field are presented.     

A Biomimetic Artificial Disc with Improved Mechanical Properties Compared to Biological Intervertebral Discs

Patients with serious spinal disc disorders will benefit from a novel artificial disc system that is suitable for clinical use in replacement arthroplasty. The disc is composed of a biomimetic three‐dimensional (3D) fabric with a triaxial fiber alignment that has superior mechanical properties when compared to conventional implants. This disc improves on the constitutional imperfections of biological intervertebral discs by eliminating the risk of rupture and delamination. The fabric bonds firmly to disc bodies, and functions in combination with bioactive bioresorbable pins and scaffolds as a stand‐alone system that maintains the position of the disc and promotes bone growth at the interface. The disc has high biocompatibility and can maintain biomimetic “J‐shaped” stress–strain behavior for up to sixty‐three million alternating stresses, which is the equivalent of natural biological movements for a period of more than 30 years. This technology exemplifies how, in the best biomaterials, biological flexibility may occasionally overcome artificial rigidity.     

Origami NdFeB Flexible Magnetic Membranes with Enhanced Magnetism and Programmable Sequences of Polarities

Permanent magnets are essential components for many biomedical systems and electromechanical devices, which may be made into flexible formats to achieve wearable monitoring and effective integration with biological tissues. However, the development of high‐performance flexible permanent magnets is challenging due to their ultrathin geometries, which contradict with the thickness‐dependent magnetic properties. In addition, magnetic membranes with controllable sequences of polarities are difficult to achieve. Here, origami techniques to achieve flexible permanent magnetic membranes with enhanced magnetic field strength and programmable sequences of polarities are presented. Linear Halbach arrays, circular Halbach arrays, and concentric magnets with thicknesses ranging from 130 to 500 µm and bending curvatures ranging from 0.039 to 0.0043 µm^?1 are achieved through different folding mechanisms. The origami membranes offer a maximum field intensity of 72 mT and extremely strong magnetic force of 0.21 N cm^?2, allowing various novel applications demonstrated through electronics interfacing, cell manipulations, and soft robotics. The origami techniques offer large magnetism and complex spatial field distribution, and enable practical use of thin flexible magnetic membranes in constructing miniaturized or even flexible electromechanical systems and biomedical instruments for magnetic resonance imaging, targeted drug delivery, health monitoring, and cancer therapy.     

Engineering Molecular Machines for the Control of Cellular Functions for Diagnostics and Therapeutics

The utilization of live cells as therapeutic materials provides controllability and complexity unmatched by small molecules and biologic agents. Recent advancements have shown that the manipulation of live cells can allow the development of powerful tools for the diagnosis of disease, production of biologics, and application as therapeutics. The field of cellular engineering has rapidly evolved and advanced to provide immuno‐oncological relief through various genetic circuits and targeting motifs. In utilizing living materials comprised of cells, complex reactions and responsive elements can be created to generate novel controllable systems. This review discusses the general principles of cellular engineering in the clinical space and highlights its utilization in chimeric antigen receptor (CAR) T‐cell therapy. In particular, the review focuses on the control systems implemented on CAR T‐cells to mitigate adverse effects and increase the potency of therapy.