Biomimetic piezoelectric nanomaterial-modified oral microrobots for targeted catalytic and immunotherapy of colorectal cancer.

Lactic acid (LA) accumulation in the tumor microenvironment poses notable challenges to effective tumor immunotherapy. Here, an intelligent tumor treatment microrobot based on the unique physiological structure and metabolic characteristics of Veillonella atypica (VA) is proposed by loading Staphylococcus aureus cell membrane-coating BaTiO3 nanocubes (SAM@BTO) on the surface of VA cells (VA-SAM@BTO) via click chemical reaction. Following oral administration, VA-SAM@BTO accurately targeted orthotopic colorectal cancer through inflammatory targeting of SAM and hypoxic targeting of VA. Under in vitro ultrasonic stimulation, BTO catalyzed two reduction reactions (O2 → •O2- and CO2 → CO) and three oxidation reactions (H2O → •OH, GSH → GSSG, and LA → PA) simultaneously, effectively inducing immunogenic death of tumor cells. BTO catalyzed the oxidative coupling of VA cells metabolized LA, effectively disrupting the immunosuppressive microenvironment, improving dendritic cell maturation and macrophage M1 polarization, and increasing effector T cell proportions while decreasing regulatory T cell numbers, which facilitates synergetic catalysis and immunotherapy.

Cell-adhesive double network self-healing hydrogel capable of cell and drug encapsulation: New platform to construct biomimetic environment with bottom-up approach.

This study presents the development and characterization of a novel double-network self-healing hydrogel based on N-carboxyethyl chitosan (CEC) and oxidized dextran (OD) with the incorporation of crosslinked collagen (CEC-OD/COL-GP) to enhance its biological and physicochemical properties. The hydrogel formed via dynamic imine bond formation exhibited efficient self-healing within 30 min, and a compressive modulus recovery of 92 % within 2 h. In addition to its self-healing ability, CEC-OD/COL-GP possesses unique physicochemical characteristics including transparency, injectability, and adhesiveness to various substrates and tissues. Cell encapsulation studies confirmed the biocompatibility and suitability of the hydrogel as a cell-culture scaffold, with the presence of a collagen network that enhances cell adhesion, spreading, long-term cell viability, and proliferation. Leveraging their unique properties, we engineered assemblies of self-healing hydrogel modules for controlled spatiotemporal drug delivery and constructed co-culture models that simulate angiogenesis in tumor microenvironments. Overall, the CEC-OD/COL-GP hydrogel is a versatile and promising material for biomedical applications, offering a bottom-up approach for constructing complex structures with self-healing capabilities, controlled drug release, and support for diverse cell types in 3D environments. This hydrogel platform has considerable potential for advancements in tissue engineering and therapeutic interventions.

Biominerals and Bioinspired Materials in Biosensing: Recent Advancements and Applications.

Inspired by nature's remarkable ability to form intricate minerals, researchers have unlocked transformative strategies for creating next-generation biosensors with exceptional sensitivity, selectivity, and biocompatibility. By mimicking how organisms orchestrate mineral growth, biomimetic and bioinspired materials are significantly impacting biosensor design. Engineered bioinspired materials offer distinct advantages over their natural counterparts, boasting superior tunability, precise controllability, and the ability to integrate specific functionalities for enhanced sensing capabilities. This remarkable versatility enables the construction of various biosensing platforms, including optical sensors, electrochemical sensors, magnetic biosensors, and nucleic acid detection platforms, for diverse applications. Additionally, bioinspired materials facilitate the development of smartphone-assisted biosensing platforms, offering user-friendly and portable diagnostic tools for point-of-care applications. This review comprehensively explores the utilization of naturally occurring and engineered biominerals and materials for diverse biosensing applications. We highlight the fabrication and design strategies that tailor their functionalities to address specific biosensing needs. This in-depth exploration underscores the transformative potential of biominerals and materials in revolutionizing biosensing, paving the way for advancements in healthcare, environmental monitoring, and other critical fields.

Advances in Composite Biofilm Biomimetic Nanodrug Delivery Systems for Cancer Treatment.

Single biofilm biomimetic nanodrug delivery systems based on single cell membranes, such as erythrocytes and cancer cells, have immune evasion ability, good biocompatibility, prolonged blood circulation, and high tumor targeting. Because of the different characteristics and functions of each single cell membrane, more researchers are using various hybrid cell membranes according to their specific needs. This review focuses on several different types of biomimetic nanodrug-delivery systems based on composite biofilms and looks forward to the challenges and possible development directions of biomimetic nanodrug-delivery systems based on composite biofilms to provide reference and ideas for future research.

Research of biomimetic corrugation on the blade flutter suppression in large-scale wind turbine systems.

Aiming at the blade flutter of large horizontal-axis wind turbines, a method by utilizing biomimetic corrugation to suppress blade flutter is first proposed. By extracting the dragonfly wing corrugation, the biomimetic corrugation airfoil is constructed, finding that mapping corrugation to the airfoil pressure side has better aerodynamic performance. The influence of corrugation type, amplitudeλ, and intensity on airfoil flutter is analyzed using orthogonal experiment, which determines that theλhas the greatest influence on airfoil flutter. Based on the fluctuation range of the moment coefficient ΔCm, the optimal airfoil flutter suppression effect is obtained when the type is III,λ= 0.6, and intensity is denser (n= 13). The effective corrugation layout area in the chord direction is determined to be the leading edge, and the ΔCmof corrugation airfoil is reduced by 7.405%, compared to the original airfoil. The application of this corrugation to NREL 15 MW wind turbine 3D blades is studied, and the influence of corrugation layout length in the blade span direction on the suppressive effect is analyzed by fluid-structure interaction. It is found that when the layout length is 0.85 R, the safety marginSfreaches a maximum value of 0.3431 Hz, which is increased 2.940%. The results show that the biomimetic corrugated structure proposed in this paper can not only improve the aerodynamic performance by changing the local flow field on the surface of the blade, but also increase the structural stiffness of the blade itself, and achieve the effect of flutter suppression.

Design and control of jumping microrobots with torque reversal latches.

Jumping microrobots and insects power their impressive leaps through systems of springs and latches. Using springs and latches, rather than motors or muscles, as actuators to power jumps imposes new challenges on controlling the performance of the jump. In this paper, we show how tuning the motor and spring relative to one another in a torque reversal latch can lead to an ability to control jump output, producing either tuneable (variable) or stereotyped jumps. We develop and utilize a simple mathematical model to explore the underlying design, dynamics, and control of a torque reversal mechanism, provides the opportunity to achieve different outcomes through the interaction between geometry, spring properties, and motor voltage. We relate system design and control parameters to performance to guide the design of torque reversal mechanisms for either variable or stereotyped jump performance. We then build a small (356 mg) microrobot and characterize the constituent components (e.g. motor and spring). Through tuning the actuator and spring relative to the geometry of the torque reversal mechanism, we demonstrate that we can achieve jumping microrobots that both jump with different take-off velocities given the actuator input (variable jumping), and those that jump with nearly the same take-off velocity with actuator input (stereotyped jumping). The coupling between spring characteristics and geometry in this system has benefits for resource-limited microrobots, and our work highlights design combinations that have synergistic impacts on output, compared to others that constrain it. This work will guide new design principles for enabling control in resource-limited jumping microrobots.

Investigation of the resilience of cyclically actuated pine cone scales ofPinus jeffreyi.

The resilience of pine cone scales has been investigated in the context of current architectural efforts to develop bioinspired passive façade shading systems that can help regulate the indoor climate. As previously shown for other species, separated tissues ofPinus jeffreyipine cone scales show independent hygroscopic bending. The blocking force that pine cone scales can generate during a closing movement is shown to be affected by the length, width and mass of the scales. After cyclically actuating pine cone scales by submerging and drying them for 102 cycles and comparing their functional characteristics measured in the undamaged and damaged state, they were still able to achieve 97% of their undamaged blocking force and torque and over 94% of their undamaged opening angle. Despite evidence of cracking within the sclereid cell layer and extensive delamination of sclerenchyma fibres, no loss of function was observed in any tested pine cone scale. This functional resilience and robustness may allowP. jeffreyitrees to continue seed dispersal for longer periods of time and to reliably protect seeds that have not yet been released. These results have contributed to a better understanding of the pine cone scale and may provide inspiration for further improving the long-term performance of passive, hygro-sensitive façade shading systems.

Shoulder viscoelasticity in a raptor-inspired model alleviates instability and enhances passive gust rejection.

Recent experiments with gliding raptors reveal a perplexing dichotomy: remarkably resilient gust rejection, but, at the same time, an exceptionally high degree of longitudinal instability. To resolve this incompatibility, a multiple degree of freedom model is developed with minimal requisite complexity to examine the hypothesis that the bird shoulder joint may embed essential stabilizing and preflexive mechanisms for rejecting rapid perturbations while simplifying and reducing control effort. Thus, the formulation herein is centrally premised upon distinct wing pitch and body pitch angles coupled via a Kelvin-Voigt viscoelastic shoulder joint. The model accurately exhibits empirical gust response of an unstable gliding raptor, generates biologically plausible equilibrium configurations, and the viscoelastic shoulder coupling is shown to drastically alleviate the high degree of instability predicted by conventional linear flight dynamics models. In fact, stability analysis of the model predicts a critical system timescale (the time to double amplitude of a pitch divergence mode) that is commensurate within vivomeasured latency of barn owls (Tyto alba). Active gust mitigation is studied by presupposing the owl behaves as an optimal controller. The system is under-actuated and the feedback control law is resolved in the controllable subspace using a Kalman decomposition. Importantly, control-theoretic analysis precisely identifies what discrete gust frequencies may be rapidly and passively rejected versus disturbances requiring feedback control intervention.

The Prospect of Biomimetic Immune Cell Membrane-Coated Nanomedicines for Treatment of Serious Bacterial Infections and Sepsis.

Invasive bacterial infections and sepsis are persistent global health concerns, complicated further by the escalating threat of antibiotic resistance. Over the past 40 years, collaborative endeavors to improve the diagnosis and critical care of septic patients have improved outcomes, yet grappling with the intricate immune dysfunction underlying the septic condition remains a formidable challenge. Anti-inflammatory interventions that exhibited promise in murine models failed to manifest consistent survival benefits in clinical studies through recent decades. Novel therapeutic approaches that target bacterial virulence factors, for example with monoclonal antibodies, aim to thwart pathogen-driven damage and restore an advantage to the immune system. A pioneering technology addressing this challenge is biomimetic nanoparticles-a therapeutic platform featuring nanoscale particles enveloped in natural cell membranes. Borne from the quest for a durable drug delivery system, the original red blood cell-coated nanoparticles showcased a broad capacity to absorb bacterial and environmental toxins from serum. Tailoring the membrane coating to immune cell sources imparts unique characteristics to the nanoparticles suitable for broader application in infectious disease. Their capacity to bind both inflammatory signals and virulence factors assembles the most promising sepsis therapies into a singular, pathogen-agnostic therapeutic. This review explores the ongoing work on immune cell-coated nanoparticle therapeutics for infection and sepsis. SIGNIFICANCE STATEMENT: Invasive bacterial infections and sepsis are a major global health problem made worse by expanding antibiotic resistance, meaning better treatment options are urgently needed. Biomimetic cell-membrane-coated nanoparticles are an innovative therapeutic platform that deploys a multifaceted mechanism to action to neutralize microbial virulence factors, capture endotoxins, and bind excessive host proinflammatory cytokines, seeking to reduce host tissue injury, aid in microbial clearance, and improve patient outcomes.

Nodes for modes: nodal honeycomb metamaterial enables a soft robot with multimodal locomotion.

Soft-bodied animals, such as worms and snakes, use many muscles in different ways to traverse unstructured environments and inspire tools for accessing confined spaces. They demonstrate versatility of locomotion which is essential for adaptation to changing terrain conditions. However, replicating such versatility in untethered soft-bodied robots with multimodal locomotion capabilities have been challenging due to complex fabrication processes and limitations of soft body structures to accommodate hardware such as actuators, batteries and circuit boards. Here, we present MetaCrawler, a 3D printed metamaterial soft robot designed for multimodal and omnidirectional locomotion. Our design approach facilitated an easy fabrication process through a discrete assembly of a modular nodal honeycomb lattice with soft and hard components. A crucial benefit of the nodal honeycomb architecture is the ability of its hard components, nodes, to accommodate a distributed actuation system, comprising servomotors, control circuits, and batteries. Enabled by this distributed actuation, MetaCrawler achieves five locomotion modes: peristalsis, sidewinding, sideways translation, turn-in-place, and anguilliform. Demonstrations showcase MetaCrawler's adaptability in confined channel navigation, vertical traversing, and maze exploration. This soft robotic system holds the potential to offer easy-to-fabricate and accessible solutions for multimodal locomotion in applications such as search and rescue, pipeline inspection, and space missions.

Exploring the effects of resin particle sizes on enhancing antibody binding capacity of a hybrid biomimetic ligand.

Particle size is a critical parameter of chromatographic resins that significantly affects protein separation. In this study, effects of resin particle sizes (31.26 µm, 59.85 µm and 85.22 µm named Aga-31, Aga-60 and Aga-85, respectively) on antibody adsorption capacity and separation performance of a hybrid biomimetic ligand were evaluated. Their performance was investigated through static adsorption and breakthrough assays to quantify static and dynamic binding capacity (Qmax and DBC). The static adsorption results revealed that the Qmax for hIgG was 152 mg/g resin with Aga-31, 151 mg/g resin with Aga-60, and 125 mg/g resin with Aga-85. Moreover, the DBC at 10% breakthrough for hIgG with a residence time of 2 min was determined to be 49.4 mg/mL for Aga-31, 45.9 mg/mL for Aga-60, and 38.9 mg/mL for Aga-85. The resins with smaller particle sizes exhibited significantly higher capacity compared to typical commercial agarose resins and a Protein A resin (MabSelect SuRe). Furthermore, the Aga-31 resin with the hybrid biomimetic ligand demonstrated exceptional performance in terms of IgG purity (>98%) and recovery (>96%) after undergoing 20 separation cycles from CHO cell supernatant. These findings are helpful in further chromatographic resin design for the industrial application of antibody separation and purification.

Visualized in-sensor computing.

In artificial nervous systems, conductivity changes indicate synaptic weight updates, but they provide limited information compared to living organisms. We present the pioneering design and production of an electrochromic neuromorphic transistor employing color updates to represent synaptic weight for in-sensor computing. Here, we engineer a specialized mechanism for adaptively regulating ion doping through an ion-exchange membrane, enabling precise control over color-coded synaptic weight, an unprecedented achievement. The electrochromic neuromorphic transistor not only enhances electrochromatic capabilities for hardware coding but also establishes a visualized pattern-recognition network. Integrating the electrochromic neuromorphic transistor with an artificial whisker, we simulate a bionic reflex system inspired by the longicorn beetle, achieving real-time visualization of signal flow within the reflex arc in response to environmental stimuli. This research holds promise in extending the biomimetic coding paradigm and advancing the development of bio-hybrid interfaces, particularly in incorporating color-based expressions.

Biomimetic nanodrug blocks CD73 to inhibit adenosine and boosts antitumor immune response synergically with photothermal stimulation.

Combination of tumor immunotherapy with photothermal therapy (PTT) is a feasible tactic to overcome the drawback of immunotherapy such as poor immune response. Via triggering the immunogenic cells death (ICD), PTT can stimulate the activity of immune cells, but meanwhile, the level of adenosine is elevated via the CD73-induced decomposition of ATP which is overexpressed accompanying with the PTT process, resulting in negative feedback to impair the immune stimulation. Herein, we developed a novel biomimetic photothermal nanodrug to specifically block CD73 for inhibition of adenosine production and more efficient priming of the suppressive immune microenvironments. The nanodrug, named as AptEM@CBA, is constructed by encapsulation of photothermal agent black phosphorus quantum dots (BPQDs) and selective CD73 inhibitor α, ß-Methyleneadenosine 5'-diphosphate (AMPCP) in chitosan nanogels, which are further covered with aptamer AS1411 modified erythrocyte membrane (EM) for biomimetic camouflage. With AS1411 induced active targeting and EM induced long blood circulation time, the enrichment of the nanodrug tumor sites is promoted. The photothermal treatment promotes the maturation of dendritic cells. Meanwhile, the release of AMPCP suppress the adenosine generation via CD73 blockade, alleviating the impairment of adenosine to dendritic cells and suppressing regulatory T cells, synergically stimulate the activity of T cells. The combination of CD73 blockade with PTT, not only suppresses the growth of primary implanted tumors, but also boosts strong antitumor immunity to inhibit the growth of distal tumors, providing good potential for tumor photoimmunotherapy.

Memory-electroluminescence for multiple action-potentials combination in bio-inspired afferent nerves.

The development of optoelectronics mimicking the functions of the biological nervous system is important to artificial intelligence. This work demonstrates an optoelectronic, artificial, afferent-nerve strategy based on memory-electroluminescence spikes, which can realize multiple action-potentials combination through a single optical channel. The memory-electroluminescence spikes have diverse morphologies due to their history-dependent characteristics and can be used to encode distributed sensor signals. As the key to successful functioning of the optoelectronic, artificial afferent nerve, a driving mode for light-emitting diodes, namely, the non-carrier injection mode, is proposed, allowing it to drive nanoscale light-emitting diodes to generate a memory-electroluminescence spikes that has multiple sub-peaks. Moreover, multiplexing of the spikes can be obtained by using optical signals with different wavelengths, allowing for a large signal bandwidth, and the multiple action-potentials transmission process in afferent nerves can be demonstrated. Finally, sensor-position recognition with the bio-inspired afferent nerve is developed and shown to have a high recognition accuracy of 98.88%. This work demonstrates a strategy for mimicking biological afferent nerves and offers insights into the construction of artificial perception systems.

Thyroid hormone induces ossification and terminal maturation in a preserved OA cartilage biomimetic model.

OBJECTIVE: To characterize aspects of triiodothyronine (T3) induced chondrocyte terminal maturation within the molecular osteoarthritis pathophysiology using the previously established T3 human ex vivo osteochondral explant model. DESIGNS: RNA-sequencing was performed on explant cartilage obtained from OA patients (n = 8), that was cultured ex vivo with or without T3 (10 ng/ml), and main findings were validated using RT-qPCR in an independent sample set (n = 22). Enrichment analysis was used for functional clustering and comparisons with available OA patient RNA-sequencing and GWAS datasets were used to establish relevance for OA pathophysiology by linking to OA patient genomic profiles. RESULTS: Besides the upregulation of known hypertrophic genes EPAS1 and ANKH, T3 treatment resulted in differential expression of 247 genes with main pathways linked to extracellular matrix and ossification. CCDC80, CDON, ANKH and ATOH8 were among the genes found to consistently mark early, ongoing and terminal maturational OA processes in patients. Furthermore, among the 37 OA risk genes that were significantly affected in cartilage by T3 were COL12A1, TNC, SPARC and PAPPA. CONCLUSIONS: RNA-sequencing results show that metabolic activation and recuperation of growth plate morphology are induced by T3 in OA chondrocytes, indicating terminal maturation is accelerated. The molecular mechanisms involved in hypertrophy were linked to all stages of OA pathophysiology and will be used to validate disease models for drug testing.

Asymmetric fin shape changes swimming dynamics of ancient marine reptiles' soft robophysical models.

Animals have evolved highly effective locomotion capabilities in terrestrial, aerial, and aquatic environments. Over life's history, mass extinctions have wiped out unique animal species with specialized adaptations, leaving paleontologists to reconstruct their locomotion through fossil analysis. Despite advancements, little is known about how extinct megafauna, such as the Ichthyosauria one of the most successful lineages of marine reptiles, utilized their varied morphologies for swimming. Traditional robotics struggle to mimic extinct locomotion effectively, but the emerging soft robotics field offers a promising alternative to overcome this challenge. This paper aims to bridge this gap by studyingMixosauruslocomotion with soft robotics, combining material modeling and biomechanics in physical experimental validation. Combining a soft body with soft pneumatic actuators, the soft robotic platform described in this study investigates the correlation between asymmetrical fins and buoyancy by recreating the pitch torque generated by extinct swimming animals. We performed a comparative analysis of thrust and torque generated byCarthorhyncus,Utatsusaurus,Mixosaurus,Guizhouichthyosaurus, andOphthalmosaurustail fins in a flow tank. Experimental results suggest that the pitch torque on the torso generated by hypocercal fin shapes such as found in model systems ofGuizhouichthyosaurus,MixosaurusandUtatsusaurusproduce distinct ventral body pitch effects able to mitigate the animal's non-neutral buoyancy. This body pitch control effect is particularly pronounced inGuizhouichthyosaurus, which results suggest would have been able to generate high ventral pitch torque on the torso to compensate for its positive buoyancy. By contrast, homocercal fin shapes may not have been conducive for such buoyancy compensation, leaving torso pitch control to pectoral fins, for example. Across the range of the actuation frequencies of the caudal fins tested, resulted in oscillatory modes arising, which in turn can affect the for-aft thrust generated.

A toe-inspired rigid-flexible coupling wheel design method for improving the terrain adaptability of a sewer robot.

The human toe, characterized by its rigid-flexible structure comprising hard bones and flexible joints, facilitates adaptive and stable movement across varied terrains. In this paper, we utilized a motion capture system to study the adaptive adjustments of toe joints when encountering obstacles. Inspired by the mechanics of toe joints, we proposed a novel design method for a rigid-flexible coupled wheel. The wheel comprises multiple elements: a rigid skeleton, supporting toes, connecting shafts, torsion springs, soft tendons, and damping pads. The torsion springs connect the rigid frame to the supporting toes, enabling them to adapt to uneven terrains and pipes with different diameters. The design was validated through kinematic and dynamic modeling, rigid-flexible coupled dynamics simulation, and stress analysis. Different stiffness coefficients of torsion springs were compared for optimal wheel design. Then, the wheel was applied to a sewer robot, and its performance was evaluated and compared with a pneumatic rubber tire in various experiments, including movement on flat surfaces, overcoming small obstacles, adaptability tests in different terrains, and active driving force tests in dry and wet pipelines. The results prove that the designed wheel showed better stability and anti-slip properties than conventional tires, making it suitable for diverse applications such as pipeline robots, desert vehicles, and lunar rovers.

Biomimetic and multifunctional nanocomposites for precision fungi theranostics.

Fungi infection is a serious threat to public health, but an effective antifungal strategy remains a challenge. Herein, a biomimetic nanocomposite with multifunctionalities, including fungi diagnosis, antifungal adhesion, precise fungi elimination, and cytokine sequestration, is constructed for battling Candida albicans (C. albicans) infection. By screening a range of cells, we find that the polarized macrophage cells have the strongest binding tendency toward C. albicans. Thus, their membranes were exfoliated to camouflage UCNPs and then decorated with photosensitizers (methylene blue, MB) and DNA sensing elements. The resulting nanocomposite can tightly bind to fungal surfaces, promote DNA recognition, and squeeze pro-inflammatory cytokines to relieve inflammation. Consequently, this nanocomposite can detect C. albicans with enhanced sensitivity and precisely eliminate fungal cells through photodynamic therapy with minimal phototoxicity because of its switchable fluorescence behavior. The developed nanocomposite with good biocompatibility achieves a satisfactory diagnostic and therapeutic effect in a C. albicans-infected mouse model, which offers a unique approach to fight fungi infection.

Porous structures inspired by porcupine quill: multiscale design optimization approach.

This paper presents a novel approach for designing a freeform bending-resistant structure from the combination of explicit discrete component-based topology optimization (TO) and the porcupine quill-inspired features. To embed the porcupine quill's features into the TO formulations, the method involves constructing discrete components at various scales to imitate features including solid shell, stochastically distributed pores, and graded stiffeners. The components are iteratively updated, and the optimization process allows for the grading of quill-inspired features while achieving optimal structural compliance under bending loads. The proposed approach is demonstrated to be effective through the resolution of Messershmitt-Bolkow-Blohm (MBB) beam designs, parameterized studies of geometric parameters, and numerical validation of long-span and short-span quill-inspired beam designs. By examining the von Mises stress distribution, the study highlights the mitigation of material yielding at the shell region brought by the geometric features of porcupine quills, leading to the potential theory support for the bending resistance. The optimized MBB beams are manufactured using the material extrusion technique, and three-point bending tests are conducted to explore the failure mitigation capability of the quill-inspired beam under large deformation. Consequently, the study concludes that the proposed quill-inspired component-based TO approach can design a structure with excellent bending resistance according to the improved energy absorption as well as increased deformation after reaching 75% peak load.