A virtuous cycle between invertebrate and robotics research: perspective on a decade of Living Machines research.

Many invertebrates are ideal model systems on which to base robot design principles due to their success in solving seemingly complex tasks across domains while possessing smaller nervous systems than vertebrates. Three areas are particularly relevant for robot designers: Research on flying and crawling invertebrates has inspired new materials and geometries from which robot bodies (their morphologies) can be constructed, enabling a new generation of softer, smaller, and lighter robots. Research on walking insects has informed the design of new systems for controlling robot bodies (their motion control) and adapting their motion to their environment without costly computational methods. And research combining wet and computational neuroscience with robotic validation methods has revealed the structure and function of core circuits in the insect brain responsible for the navigation and swarming capabilities (their mental faculties) displayed by foraging insects. The last decade has seen significant progress in the application of principles extracted from invertebrates, as well as the application of biomimetic robots to model and better understand how animals function. This Perspectives paper on the past 10 years of the Living Machines conference outlines some of the most exciting recent advances in each of these fields before outlining lessons gleaned and the outlook for the next decade of invertebrate robotic research.

Cervical non-fusion using biomimetic artificial disc and vertebra complex: technical innovation and biomechanics analysis.

BACKGROUND: Changes in spinal mobility after vertebral fusion are important factors contributing to adjacent vertebral disease (ASD). As an implant for spinal non-fusion, the motion-preserving prosthesis is an effective method to reduce the incidence of ASD, but its deficiencies hamper the application in clinical. This study designs a novel motion-preserving artificial cervical disc and vertebra complex with an anti-dislocation mechanism (MACDVC-AM) and verifies its effect on the cervical spine. METHODS: The MACDVC-AM was designed on the data of healthy volunteers. The finite element intact model, fusion model, and MACDVC-AM model were constructed, and the range of motion (ROM) and stress of adjacent discs were compared. The biomechanical tests were performed on fifteen cervical specimens, and the stability index ROM (SI-ROM) were calculated. RESULTS: Compared with the intervertebral ROMs of the intact model, the MACDVC-AM model reduced by 28-70% in adjacent segments and increased by 26-54% in operated segments, but the fusion model showed the opposite result. In contrast to the fusion model, the MACDVC-AM model diminished the stress of adjacent intervertebral discs. In biomechanical tests, the MACDVC-AM group showed no significant difference with the ROMs of the intact group (p > 0.05). The SI-ROM of the MACDVC-AM group is negative but close to zero and showed no significant difference with the intact group (p > 0.05). CONCLUSIONS: The MACDVC-AM was successfully designed. The results indicate that the MACDVC-AM can provide physiological mobility and stability, reduce adjacent intervertebral compensatory motion, and alleviate the stress change of adjacent discs, which contributes to protect adjacent discs and reduce the occurrence of ASD.

The rise of intelligent matter.

Artificial intelligence (AI) is accelerating the development of unconventional computing paradigms inspired by the abilities and energy efficiency of the brain. The human brain excels especially in computationally intensive cognitive tasks, such as pattern recognition and classification. A long-term goal is de-centralized neuromorphic computing, relying on a network of distributed cores to mimic the massive parallelism of the brain, thus rigorously following a nature-inspired approach for information processing. Through the gradual transformation of interconnected computing blocks into continuous computing tissue, the development of advanced forms of matter exhibiting basic features of intelligence can be envisioned, able to learn and process information in a delocalized manner. Such intelligent matter would interact with the environment by receiving and responding to external stimuli, while internally adapting its structure to enable the distribution and storage (as memory) of information. We review progress towards implementations of intelligent matter using molecular systems, soft materials or solid-state materials, with respect to applications in soft robotics, the development of adaptive artificial skins and distributed neuromorphic computing.

Application of 3D bioprinting in the prevention and the therapy for human diseases.

Rapid development of vaccines and therapeutics is necessary to tackle the emergence of new pathogens and infectious diseases. To speed up the drug discovery process, the conventional development pipeline can be retooled by introducing advanced in vitro models as alternatives to conventional infectious disease models and by employing advanced technology for the production of medicine and cell/drug delivery systems. In this regard, layer-by-layer construction with a 3D bioprinting system or other technologies provides a beneficial method for developing highly biomimetic and reliable in vitro models for infectious disease research. In addition, the high flexibility and versatility of 3D bioprinting offer advantages in the effective production of vaccines, therapeutics, and relevant delivery systems. Herein, we discuss the potential of 3D bioprinting technologies for the control of infectious diseases. We also suggest that 3D bioprinting in infectious disease research and drug development could be a significant platform technology for the rapid and automated production of tissue/organ models and medicines in the near future.

Injecting Information into the Mammalian Cortex: Progress, Challenges, and Promise.

For 150 years artificial stimulation has been used to study the function of the nervous system. Such stimulation-whether electrical or optogenetic-eventually may be used in neuroprosthetic devices to replace lost sensory inputs and to otherwise introduce information into the nervous system. Efforts toward this goal can be classified broadly as either biomimetic or arbitrary. Biomimetic stimulation aims to mimic patterns of natural neural activity, so that the subject immediately experiences the artificial stimulation as if it were natural sensation. Arbitrary stimulation, in contrast, makes no attempt to mimic natural patterns of neural activity. Instead, different stimuli-at different locations and/or in different patterns-are assigned different meanings randomly. The subject's time and effort then are required to learn to interpret different stimuli, a process that engages the brain's inherent plasticity. Here we will examine progress in using artificial stimulation to inject information into the cerebral cortex and discuss the challenges for and the promise of future development.

Metal or muscle? The future of biologically inspired robots.

Biology has inspired the development of agile robots, and it is now teaching us how to grow machines from living cells.

A vision for future bioinspired and biohybrid robots.

Bioinspired and biohybrid robots can help respond to diverse, sustainable application needs.

Biomimetic two-dimensional nanozymes: synthesis, hybridization, functional tailoring, and biosensor applications.

Biological enzymes play important roles in mediating the biological reactions in vitro and in vivo due to their high catalytic activity, strong bioactivity, and high specificity; however, they have also some disadvantages such as high cost, low environmental stability, weak reusability, and difficult production. To overcome these shortcomings, functional nanomaterials including metallic nanoparticles, single atoms, metal oxides, alloys, and others have been utilized as nanozymes to mimic the properties and functions of natural enzymes. Due to the development of the synthesis and applications of two-dimensional (2D) materials, 2D nanomaterials have shown high potential to be used as novel nanozymes in biosensing, bioimaging, therapy, logic gates, and environmental remediation due to their unique physical, chemical, biological, and electronic properties. In this work, we summarize recent advances in the preparation and functionalization, as well as biosensor and immunoassay applications of various 2D material-based nanozymes. To achieve this aim, first we demonstrate the preparation strategies of 2D nanozymes such as chemical reduction, templated synthesis, chemical exfoliation, calcination, electrochemical deposition, hydrothermal synthesis, and many others. Meanwhile, the structure and properties of the 2D nanozymes prepared by conjugating 2D materials with nanoparticles, metal oxides, biomolecules, polymers, ions, and 2D heteromaterials are introduced and discussed in detail. Then, the applications of the prepared 2D nanozymes in colorimetric, electrochemical, fluorescent, and electrochemiluminescent sensors are demonstrated.

Artificial Metalloenzymes: Recent Developments and Innovations in Bioinorganic Catalysis.

Cellular life is orchestrated by the biochemical components of cells that include nucleic acids, lipids, carbohydrates, proteins, and cofactors such as metabolites and metals, all of which coalesce and function synchronously within the cell. Metalloenzymes allow for such complex chemical processes, as they catalyze a myriad of biochemical reactions both efficiently and selectively, where the metal cofactor provides additional functionality to promote reactivity not readily achieved in their absence. While the past 60 years have yielded considerable insight on how enzymes catalyze these reactions, a need to engineer and develop artificial metalloenzymes has been driven not only by industrial and therapeutic needs, but also by innate human curiosity. The design of miniature enzymes, both rationally and through serendipity, using both organic and inorganic building blocks has been explored by many scientists over the years and significant progress has been made. Herein, recent developments over the past 5 years in areas that have not been recently reviewed are summarized, and prospects for future research in these areas are addressed.

Microfluidic Skin-on-a-Chip Models: Toward Biomimetic Artificial Skin.

The role of skin in the human body is indispensable, serving as a barrier, moderating homeostatic balance, and representing a pronounced endpoint for cosmetics and pharmaceuticals. Despite the extensive achievements of in vitro skin models, they do not recapitulate the complexity of human skin; thus, there remains a dependence on animal models during preclinical drug trials, resulting in expensive drug development with high failure rates. By imparting a fine control over the microenvironment and inducing relevant mechanical cues, skin-on-a-chip (SoC) models have circumvented the limitations of conventional cell studies. Enhanced barrier properties, vascularization, and improved phenotypic differentiation have been achieved by SoC models; however, the successful inclusion of appendages such as hair follicles and sweat glands and pigmentation relevance have yet to be realized. The present Review collates the progress of SoC platforms with a focus on their fabrication and the incorporation of mechanical cues, sensors, and blood vessels.

3D Bioprinting: from Benches to Translational Applications.

Over the last decades, the fabrication of 3D tissues has become commonplace in tissue engineering and regenerative medicine. However, conventional 3D biofabrication techniques such as scaffolding, microengineering, and fiber and cell sheet engineering are limited in their capacity to fabricate complex tissue constructs with the required precision and controllability that is needed to replicate biologically relevant tissues. To this end, 3D bioprinting offers great versatility to fabricate biomimetic, volumetric tissues that are structurally and functionally relevant. It enables precise control of the composition, spatial distribution, and architecture of resulting constructs facilitating the recapitulation of the delicate shapes and structures of targeted organs and tissues. This Review systematically covers the history of bioprinting and the most recent advances in instrumentation and methods. It then focuses on the requirements for bioinks and cells to achieve optimal fabrication of biomimetic constructs. Next, emerging evolutions and future directions of bioprinting are discussed, such as freeform, high-resolution, multimaterial, and 4D bioprinting. Finally, the translational potential of bioprinting and bioprinted tissues of various categories are presented and the Review is concluded by exemplifying commercially available bioprinting platforms.

Enamel biomimetics-fiction or future of dentistry.

Tooth enamel is a complex mineralized tissue consisting of long and parallel apatite crystals configured into decussating enamel rods. In recent years, multiple approaches have been introduced to generate or regenerate this highly attractive biomaterial characterized by great mechanical strength paired with relative resilience and tissue compatibility. In the present review, we discuss five pathways toward enamel tissue engineering, (i) enamel synthesis using physico-chemical means, (ii) protein matrix-guided enamel crystal growth, (iii) enamel surface remineralization, (iv) cell-based enamel engineering, and (v) biological enamel regeneration based on de novo induction of tooth morphogenesis. So far, physical synthesis approaches using extreme environmental conditions such as pH, heat and pressure have resulted in the formation of enamel-like crystal assemblies. Biochemical methods relying on enamel proteins as templating matrices have aided the growth of elongated calcium phosphate crystals. To illustrate the validity of this biochemical approach we have successfully grown enamel-like apatite crystals organized into decussating enamel rods using an organic enamel protein matrix. Other studies reviewed here have employed amelogenin-derived peptides or self-assembling dendrimers to re-mineralize mineral-depleted white lesions on tooth surfaces. So far, cell-based enamel tissue engineering has been hampered by the limitations of presently existing ameloblast cell lines. Going forward, these limitations may be overcome by new cell culture technologies. Finally, whole-tooth regeneration through reactivation of the signaling pathways triggered during natural enamel development represents a biological avenue toward faithful enamel regeneration. In the present review we have summarized the state of the art in enamel tissue engineering and provided novel insights into future opportunities to regenerate this arguably most fascinating of all dental tissues.

Effective Differentiation of Induced Pluripotent Stem Cells Into Dental Cells.

BACKGROUND: A biotooth is defined as a complete living tooth, made in laboratory cultures from a spontaneous interplay between epithelial and mesenchymal cell-based frontal systems. A good solution to these problems is to use induced pluripotent stem cells (iPSCs). However, no one has yet formulated culture conditions that effectively differentiate iPSCs into dental epithelial and dental mesenchymal cells phenotypes analogous to those present in tooth development. RESULTS: Here, we tried to induce differentiation methods for dental epithelial cells (DEC) and dental mesenchymal cells from iPSCs. For the DEC differentiation, the conditional media of SF2 DEC was adjusted to embryoid body. Moreover, we now report on a new cultivation protocol, supported by transwell membrane cell culture that make it possible to differentiate iPSCs into dental epithelial and mesenchymal cells with abilities to initiate the first stages in de novo tooth formation. CONCLUSIONS: Implementation of technical modifications to the protocol that maximize the number and rate of iPSC differentiation, into mesenchymal and epithelial cell layers, will be the next step toward growing an anatomically accurate biomimetic tooth organ. Developmental Dynamics 248:129-139, 2019. © 2018 Wiley Periodicals, Inc.

An agent-based approach for the application of nature's forms to product conceptual design.

Given current high market competitiveness, it is necessary to differentiate between products that perform the same function. For this objective, designer can recur to various sources of inspiration in the searching of the more attractive form during the conceptual design stage. One of these sources can be nature, which offers a large number of geometries and textures that can be used from a shape point of view to help the designer in the creative process. This work presents an agent-based approach for a design-aided tool to provide users with some ideas, beginning with simple parts/concepts, and then increasing the complexity level according to the answers offered by designer. The proposed paradigm was implemented using the JADE agent-based platform. In order to validate the platform, several product categories were offered to fifteen different users and a total of sixty design proposals were obtained with the aid of the platform. After evaluating all the proposals, twelve of the sixty designs were finally selected and modelled by a Computer-Aided Design software. The obtained results demonstrate the feasibility of using an agent-based approach to obtain an adaptive intelligent solution to the product conceptual design problem.

Towards a theoretical clarification of biomimetics using conceptual tools from engineering design.

Many successful examples of biomimetic products are available, and most research efforts in this emerging field are directed towards the development of specific applications. The theoretical and conceptual underpinnings of the knowledge transfer between biologists, engineers and architects are, however, poorly investigated. The present article addresses this gap. We use a 'technomorphic' approach, i.e. the application of conceptual tools derived from engineering design, to better understand the processes operating during a typical biomimetic research project. This helps to elucidate the formal connections between functions, working principles and constructions (in a broad sense)-because the 'form-function-relationship' is a recurring issue in biology and engineering. The presented schema also serves as a conceptual framework that can be implemented for future biomimetic projects. The concepts of 'function' and 'working principle' are identified as the core elements in the biomimetic knowledge transfer towards applications. This schema not only facilitates the development of a common language in the emerging science of biomimetics, but also promotes the interdisciplinary dialogue among its subdisciplines.