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Organs-on-chips (OoCs), also known as microphysiological systems or ‘tissue chips’ (the terms are synonymous), have attracted substantial interest in recent years owing to their potential to be informative at multiple stages of the drug discovery and development process. These innovative devices could provide insights into normal human organ function and disease pathophysiology, as well as more accurately predict the safety and efficacy of investigational drugs in humans. Therefore, they are likely to become useful additions to traditional preclinical cell culture methods and in vivo animal studies in the near term, and in some cases replacements for them in the longer term. In the past decade, the OoC field has seen dramatic advances in the sophistication of biology and engineering, in the demonstration of physiological relevance and in the range of applications. These advances have also revealed new challenges and opportunities, and expertise from multiple biomedical and engineering fields will be needed to fully realize the promise of OoCs for fundamental and translational applications. This Review provides a snapshot of this fast-evolving technology, discusses current applications and caveats for their implementation, and offers suggestions for directions in the next decade.Organs-on-chips (OoCs) could be useful at various stages of drug discovery and development, providing insight regarding human organ physiology in both normal and disease contexts, as well as accurately predicting developmental drug safety and efficacy. This Review discusses the advances that have enabled OoCs to demonstrate physiological relevance, and the challenges and opportunities that need to be tackled to tap the full potential of OoC utility for translational research.

Robot designs can take many inspirations from nature, where there are many examples of highly resilient and fault-tolerant locomotion strategies to navigate complex terrains by recruiting multi-functional appendages. For example, birds such as Chukars and Hoatzins can repurpose wings for quadrupedal walking and wing-assisted incline running. These animals showcase impressive dexterity in employing the same appendages in different ways and generating multiple modes of locomotion, resulting in highly plastic locomotion traits which enable them to interact and navigate various environments and expand their habitat range. The robotic biomimicry of animals’ appendage repurposing can yield mobile robots with unparalleled capabilities. Taking inspiration from animals, we have designed a robot capable of negotiating unstructured, multi-substrate environments, including land and air, by employing its components in different ways as wheels, thrusters, and legs. This robot is called the Multi-Modal Mobility Morphobot, or M4 in short. M4 can employ its multi-functional components composed of several actuator types to (1) fly, (2) roll, (3) crawl, (4) crouch, (5) balance, (6) tumble, (7) scout, and (8) loco-manipulate. M4 can traverse steep slopes of up to 45 deg. and rough terrains with large obstacles when in balancing mode. M4 possesses onboard computers and sensors and can autonomously employ its modes to negotiate an unstructured environment. We present the design of M4 and several experiments showcasing its multi-modal capabilities. The biomimicry of animals’ appendage repurposing can be applied to robot designs, resulting in unparalleled capabilities. Sihite et al. report a Multi-Modal Mobility Morphobot (M4) that negotiate unstructured, multi-substrate environments, including land and air, by employing its components in different ways as wheels, thrusters, and legs.

Nanozymes are nanomaterials exhibiting intrinsic enzyme-like characteristics that have increasingly attracted attention, owing to their high catalytic activity, low cost and high stability. This combination of properties has enabled a broad spectrum of applications, ranging from biological detection assays to disease diagnosis and biomedicine development. Since the intrinsic peroxidase activity of Fe3O4 nanoparticles (NPs) was first reported in 2007, >40 types of nanozymes have been reported that possess peroxidase-, oxidase-, haloperoxidase- or superoxide dismutase–like catalytic activities. Given the complex interdependence of the physicochemical properties and catalytic characteristics of nanozymes, it is important to establish a standard by which the catalytic activities and kinetics of various nanozymes can be quantitatively compared and that will benefit the development of nanozyme-based detection and diagnostic technologies. Here, we first present a protocol for measuring and defining the catalytic activity units and kinetics for peroxidase nanozymes, the most widely used type of nanozyme. In addition, we describe the detailed experimental procedures for a typical nanozyme strip–based biological detection test and demonstrate that nanozyme-based detection is repeatable and reliable when guided by the presented nanozyme catalytic standard. The catalytic activity and kinetics assays for a nanozyme can be performed within 4 h.

This Review discusses the materials and electronic requirements for flexible sensors and electronic systems to mimic the mechanical and sensing properties of natural skin, with the goal of providing artificial prostheses with sensing capabilities. Skin plays an important role in mediating our interactions with the world. Recreating the properties of skin using electronic devices could have profound implications for prosthetics and medicine. The pursuit of artificial skin has inspired innovations in materials to imitate skin's unique characteristics, including mechanical durability and stretchability, biodegradability, and the ability to measure a diversity of complex sensations over large areas. New materials and fabrication strategies are being developed to make mechanically compliant and multifunctional skin-like electronics, and improve brain/machine interfaces that enable transmission of the skin's signals into the body. This Review will cover materials and devices designed for mimicking the skin's ability to sense and generate biomimetic signals.

Although Nature has always been a common source of inspiration in the development of artificial materials, only recently has the ability of man-made materials to produce complex three-dimensional (3D) structures from two-dimensional sheets been explored. Here we present a new approach to the self-shaping of soft matter that mimics fibrous plant tissues by exploiting small-scale variations in the internal stresses to form three-dimensional morphologies. We design single-layer hydrogel sheets with chemically distinct, fibre-like regions that exhibit differential shrinkage and elastic moduli under the application of external stimulus. Using a planar-to-helical three-dimensional shape transformation as an example, we explore the relation between the internal architecture of the sheets and their transition to cylindrical and conical helices with specific structural characteristics. The ability to engineer multiple three-dimensional shape transformations determined by small-scale patterns in a hydrogel sheet represents a promising step in the development of programmable soft matter. The complex shapes of biological tissues are often formed as a result of stress modulations. Wu et al. exploit such behaviour experimentally and theoretically to demonstrate a new mechanism of the formation of three-dimensional structures that is driven by engineered small-scale stresses within patterned hydrogel sheets.

Natural biomolecular systems have evolved to form a rich variety of supramolecular materials and machinery fundamental to cellular function. The assembly of these structures commonly involves interactions between specific molecular building blocks, a strategy that can also be replicated in an artificial setting to prepare functional materials. The self-assembly of synthetic biomimetic peptides thus allows the exploration of chemical and sequence space beyond that used routinely by biology. In this Review, we discuss recent conceptual and experimental advances in self-assembling artificial peptidic materials. In particular, we explore how naturally occurring structures and phenomena have inspired the development of functional biomimetic materials that we can harness for potential interactions with biological systems. As our fundamental understanding of peptide self-assembly evolves, increasingly sophisticated materials and applications emerge and lead to the development of a new set of building blocks and assembly principles relevant to materials science, molecular biology, nanotechnology and precision medicine. The self-assembly of biomimetic peptides can mimic complex natural systems involving whole proteins. This Review describes how synthetic peptides afford tunable scaffolds for biomineralization, drug delivery and tissue growth.

Engineered tissues can be used to model human pathophysiology and test the efficacy and safety of drugs. Yet, to model whole-body physiology and systemic diseases, engineered tissues with preserved phenotypes need to physiologically communicate. Here we report the development and applicability of a tissue-chip system in which matured human heart, liver, bone and skin tissue niches are linked by recirculating vascular flow to allow for the recapitulation of interdependent organ functions. Each tissue is cultured in its own optimized environment and is separated from the common vascular flow by a selectively permeable endothelial barrier. The interlinked tissues maintained their molecular, structural and functional phenotypes over 4 weeks of culture, recapitulated the pharmacokinetic and pharmacodynamic profiles of doxorubicin in humans, allowed for the identification of early miRNA biomarkers of cardiotoxicity, and increased the predictive values of clinically observed miRNA responses relative to tissues cultured in isolation and to fluidically interlinked tissues in the absence of endothelial barriers. Vascularly linked and phenotypically stable matured human tissues may facilitate the clinical applicability of tissue chips. Tissue chips with matured human heart, liver, bone and skin tissue niches linked by recirculating vascular flow recapitulate interdependent functions of these organs.

Advancing the spontaneous bottom-up construction of artificial cells with high organizational complexity and diverse functionality remains an unresolved issue at the interface between living and non-living matter 1 , 2 , 3 – 4 . Here, to address this challenge, we developed a living material assembly process based on the capture and on-site processing of spatially segregated bacterial colonies within individual coacervate microdroplets for the endogenous construction of membrane-bounded, molecularly crowded, and compositionally, structurally and morphologically complex synthetic cells. The bacteriogenic protocells inherit diverse biological components, exhibit multifunctional cytomimetic properties and can be endogenously remodelled to include a spatially partitioned DNA–histone nucleus-like condensate, membranized water vacuoles and a three-dimensional network of F-actin proto-cytoskeletal filaments. The ensemble is biochemically energized by ATP production derived from implanted live Escherichia coli cells to produce a cellular bionic system with amoeba-like external morphology and integrated life-like properties. Our results demonstrate a bacteriogenic strategy for the bottom-up construction of functional protoliving microdevices and provide opportunities for the fabrication of new synthetic cell modules and augmented living/synthetic cell constructs with potential applications in engineered synthetic biology and biotechnology. A bacteriogenic strategy for constructing membrane-bounded, molecularly crowded, and compositionally, structurally and morphologically complex synthetic cells provides opportunities for the fabrication of new synthetic cell modules and augmented living/synthetic cell constructs.

Miniature hydrogel compartments in scalable stacked and folded geometries were used to prepare a contact-activated artificial electric organ. Eel-y shocking power source The electric eel can generate electrical discharges of 100 watts to stun prey, but should you X-ray an eel, you wouldn't find a battery pack inside. Instead, thousands of cells called electrocytes are arranged along its body, each producing a small ion gradient and therefore a potential difference across them. Now, Michael Mayer and colleagues have developed a hydrogel-based system that mimics the electrocyte mechanism and could be used as a soft power source for robotics. They arrange sets of ion-selective hydrogels in series to generate ion gradients across a group of four hydrogel droplets. These droplets can either be arranged in series in a microfluidic set-up, or be stacked in parallel by folding up an array of hydrogels using origami principles. The net result is a power source that is able to generate voltages similar to those generated by the electric eel. Progress towards the integration of technology into living organisms requires electrical power sources that are biocompatible, mechanically flexible, and able to harness the chemical energy available inside biological systems. Conventional batteries were not designed with these criteria in mind. The electric organ of the knifefish Electrophorus electricus (commonly known as the electric eel) is, however, an example of an electrical power source that operates within biological constraints while featuring power characteristics that include peak potential differences of 600 volts and currents of 1 ampere 1 , 2 . Here we introduce an electric-eel-inspired power concept that uses gradients of ions between miniature polyacrylamide hydrogel compartments bounded by a repeating sequence of cation- and anion-selective hydrogel membranes. The system uses a scalable stacking or folding geometry that generates 110 volts at open circuit or 27 milliwatts per square metre per gel cell upon simultaneous, self-registered mechanical contact activation of thousands of gel compartments in series while circumventing power dissipation before contact. Unlike typical batteries, these systems are soft, flexible, transparent, and potentially biocompatible. These characteristics suggest that artificial electric organs could be used to power next-generation implant materials such as pacemakers, implantable sensors, or prosthetic devices in hybrids of living and non-living systems 3 , 4 , 5 , 6 .

The authors would like to acknowledge financial support from the European Research Council, grant agreement ERC-2012-ADG 20120216-321266 (project ComplexiTE). C.F.G. acknowledges scholarship grant no. PD/BD/135253/2017 from Fundação para a Ciência e Tecnologia (FCT). The authors also thank the peer-reviewers for the constructive comments and suggestions that helped to shape this manuscript.