Evolution of the Microrobots: Stimuli-Responsive Materials and Additive Manufacturing Technologies Turn Small Structures into Microscale Robots.

The development of functional microsystems and microrobots that have characterized the last decade is the result of a synergistic and effective interaction between the progress of fabrication techniques and the increased availability of smart and responsive materials to be employed in the latter. Functional structures on the microscale have been relevant for a vast plethora of technologies that find application in different sectors including automotive, sensing devices, and consumer electronics, but are now also entering medical clinics. Working on or inside the human body requires increasing complexity and functionality on an ever-smaller scale, which is becoming possible as a result of emerging technology and smart materials over the past decades. In recent years, additive manufacturing has risen to the forefront of this evolution as the most prominent method to fabricate complex 3D structures. In this review, we discuss the rapid 3D manufacturing techniques that have emerged and how they have enabled a great leap in microrobotic applications. The arrival of smart materials with inherent functionalities has propelled microrobots to great complexity and complex applications. We focus on which materials are important for actuation and what the possibilities are for supplying the required energy. Furthermore, we provide an updated view of a new generation of microrobots in terms of both materials and fabrication technology. While two-photon lithography may be the state-of-the-art technology at the moment, in terms of resolution and design freedom, new methods such as two-step are on the horizon. In the more distant future, innovations like molecular motors could make microscale robots redundant and bring about nanofabrication.

Preparation of different conjugated polymers characterized by complementary electronic properties from an identical precursor.

The possibility of generating regions with different electronic properties within the same organic semiconductor thin film could offer novel opportunities for designing and fabricating organic electronic devices and circuits. This study introduces a new approach based on a novel type of highly processable polymer precursor that can yield two different conjugated polymers characterized by complementary electronic properties, i.e. promoting electron or hole transport, from the same starting material. In particular, these multipotent precursors comprise functionalized dihydroanthracene units that can offer several functionalization opportunities to improve the solubility or insert specific functionalities. This strategy also allows for the preparation of high-molecular-weight conjugated polymers comprising diethynylanthracene and anthraquinone units without the need for solubilizing side chains. Thin films of the polymer precursor can be used, after solid-state transformations, to prepare single organic layers comprising regions characterized by different chemical nature and electronic properties. Here, we present a detailed characterization of the chemical and electronic properties of the precursor and the obtained conjugated polymers, showing how it is possible to harvest their characteristics for potential applications such as electrochromic surfaces and organic field-effect transistors.

Polyketone-Based Anion-Exchange Membranes for Alkaline Water Electrolysis.

Anion-exchange membranes (AEMs) are involved in a wide range of applications, including fuel cells and water electrolysis. A straightforward method for the preparation of efficient AEMs consists of polymer functionalization with robust anion-exchange sites. In this work, an aliphatic polyketone was functionalized with 1-(3-aminopropyl)imidazole through the Paal-Knorr reaction, with a carbonyl (CCO %) conversion of 33%. The anion-exchange groups were generated by the imidazole quaternization by using two different types of alkyl halides, i.e., 1,4-iodobutane and 1-iodobutane, with the aim of modulating the degree of crosslinking of the derived membrane. All of the membranes were amorphous (Tg ∼ 30 °C), thermally resistant up to 130 °C, and had a minimum Young's modulus of 372 ± 30 MPa and a maximum of 86 ± 5 % for the elongation at break for the least-crosslinked system. The ionic conductivity of the AEMs was determined at 25 °C by electrochemical impedance spectroscopy (EIS), with a maximum of 9.69 mS/cm, i.e., comparable with that of 9.66 mS/cm measured using a commercially available AEM (Fumasep-PK-130). Future efforts will be directed toward increasing the robustness of these PK-based AEMs to meet all the requirements needed for their application in electrolytic cells.

Sensing Technologies for Extravasation Detection: A Review.

Peripheral intravenous catheters are administered for various purposes, such as blood sampling or the infusion of contrast agents and drugs. Extravasation happens when the catheter is unintentionally directed outside of the vein due to movement of the intravascular catheter, enhanced vascular permeability, or occlusion of the upstream vein. In this article, extravasation and its mechanism are discussed. Subsequently, the sensorized devices (e.g., single sensor and multimodal detection) to identify the extravasation phenomena are highlighted. In this review article, we have shed light on both physiological and engineering points of view of extravasation and its detection approaches. This review provides an overview on the most recent and relevant technologies that can help in the early detection of extravasation.

Recapitulating Antioxidant and Antibacterial Compounds into a Package for Tissue Regeneration: Dual Function Materials with Synergistic Effect.

Oxidative damage and infection can prevent or delay tissue repair. Moreover, infection reinforces reactive oxygen species (ROS) formation, which makes the wound's condition even worse. Therefore, the need for antioxidant and antibacterial agents is felt for tissue regeneration. There are emerging up-and-coming biomaterials that recapitulate both properties into a package, offering an effective solution to turn the wound back into a healing state. In this article, the principles of antioxidant and antibacterial activity are summarized. The review starts with biological aspects, getting the readers to familiarize themselves with tissue barriers against infection. This is followed by the chemistry and mechanism of action of antioxidant and antibacterial materials (dual function). Eventually, the outlook and challenges are underlined to provide where the dual-function biomaterials are and where they are going in the future. It is expected that the present article inspires the designing of dual-function biomaterials to more advanced levels by providing the fundamentals and comparative points of view and paving the clinical way for these materials.

Enhancing Methotrexate Delivery in the Brain by Mesoporous Silica Nanoparticles Functionalized with Cell-Penetrating Peptide using in Vivo and ex Vivo Monitoring.

The blood-brain barrier (BBB) acts as a physical/biochemical barrier that protects brain parenchyma from potential hazards exerted by different xenobiotics found in the systemic circulation. This barrier is created by "a lipophilic gate" as well as a series of highly organized influx/efflux mechanisms. The BBB bottleneck adversely affects the efficacy of chemotherapeutic agents in treating different CNS malignancies such as glioblastoma, an aggressive type of cancer affecting the brain. In the present study, mesoporous silica nanoparticles (MSNs) were conjugated with the transactivator of transcription (TAT) peptide, a cell-penetrating peptide, to produce MSN-NH-TAT with the aim of improving methotrexate (MTX) penetration into the brain. The TAT-modified nanosystem was characterized by Fourier transform infrared spectrometry (FTIR), field emission scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM), atomic force microscopy (AFM), dynamic light scattering (DLS), and N2 adsorption-desorption analysis. In vitro hemolysis and cell viability studies confirmed the biocompatibility of the MSN-based nanocarriers. In addition, in vivo studies showed that the MTX-loaded MSN-NH-TAT improved brain-to-plasma concentration ratio, brain uptake clearance, and the drug's blood terminal half-life, compared with the use of free MTX. Taken together, the results of the present study indicate that MSN functionalization with TAT is crucial for delivery of MTX into the brain. The present nanosystem represents a promising alternative drug carrier to deliver MTX into the brain via overcoming the BBB.

Engineering and Development of a Tissue Model for the Evaluation of Microneedle Penetration Ability, Drug Diffusion, Photothermal Activity, and Ultrasound Imaging: A Promising Surrogate to Ex Vivo and In Vivo Tissues.

Driven by regulatory authorities and the ever-growing demands from industry, various artificial tissue models have been developed. Nevertheless, there is no model to date that is capable of mimicking the biomechanical properties of the skin whilst exhibiting the hydrophilicity/hydrophobicity properties of the skin layers. As a proof-of-concept study, tissue surrogates based on gel and silicone are fabricated for the evaluation of microneedle penetration, drug diffusion, photothermal activity, and ultrasound bioimaging. The silicone layer aims to imitate the stratum corneum while the gel layer aims to mimic the water-rich viable epidermis and dermis present in in vivo tissues. The diffusion of drugs across the tissue model is assessed, and the results reveal that the proposed tissue model shows similar behavior to a cancerous kidney. In place of typical in vitro aqueous solutions, this model can also be employed for evaluating the photoactivity of photothermal agents since the tissue model shows a similar heating profile to skin of mice when irradiated with near-infrared laser. In addition, the designed tissue model exhibits promising results for biomedical applications in optical coherence tomography and ultrasound imaging. Such a tissue model paves the way to reduce the use of animals testing in research whilst obviating ethical concerns.

Functionalized aliphatic polyketones with germicide activity.

The COVID-19 pandemic has further confirmed to the community that direct contact with contaminated surfaces and objects represents an important source of pathogen spreading among humans. Therefore, it is of paramount importance to design effective germicidal paints to ensure a rapid and potent disinfectant action of surfaces. In this work, we design novel germicide polymeric coatings by inserting quaternary ammonium and sugar groups on the macromolecular backbone, thus respectively endowing the polymer with germicide features and hydrophilicity to interact with the surfaces. An aliphatic polyketone was selected as a starting polymer matrix that was functionalized with primary amine derivatives via the Paal-Knorr reaction. The resulting polymers were deposited on cellulose filter papers and checkboard charts with excellent coating yield and substrate coverage as determined by scanning electron microscopy for cellulose. Remarkably, the substrates coated by the functional polymers bearing quaternary ammonium compounds showed excellent bactericide properties with antibacterial rate of 99% and logarithmic reduction of >3. Notably, the polymers with higher hydrophobicity showed better retention on the substrate after being treated with water at neutral pH.

Injectable Antibacterial Gelatin-Based Hydrogel Incorporated with Two-Dimensional Nanosheets for Multimodal Healing of Bacteria-Infected Wounds.

The design and development of multifunctional injectable hydrogels with high photothermal antibacterial activity and shape adaptability to accelerate bacteria-infected wound healing is of critical importance in clinical applications. In this study, a hybrid hydrogel composed of gelatin, iron, and MnO2 nanosheets was prepared by multiple interactions, including coordinative and hydrogen bonding as well as electrostatic attraction. The introduced MnO2 and Fe components made the hydrogels photothermally and chemodynamically active, thereby endowing them with potent antibacterial capabilities against both Gram-negative and Gram-positive bacteria. Because of the Fenton activity of the hydrogels, they could produce abandoned oxygen, which is highly crucial in the healing process of wounds. They also showed good cytocompatibility and hemocompatibility as well as high hemostatic properties. Moreover, the injectable hydrogels could fill irregular wounds and significantly accelerate bacteria-infected wound healing through decreasing the inflammatory response and increasing blood vessels. These features indicated the promising potential of the multifunctional hydrogel for healing infected full-thickness wounds.

Invisible Thermoplasmonic Indium Tin Oxide Nanoparticle Ink for Anti-counterfeiting Applications.

In this study, we present a thermoplasmonic transparent ink based on a colloidal dispersion of indium tin oxide (ITO) nanoparticles, which can offer several advantages as anti-counterfeiting technology. The custom ink could be directly printed on several substrates, and it is transparent under visible light but is able to generate heat by absorption of NIR radiation. Dynamic temperature mapping of the printed motifs was performed by using a thermal camera while irradiating the samples with an IR lamp. The printed samples presented fine features (in the order of 75 µm) and high thermal resolution (of about 250 µm). The findings are supported by thermal finite-element simulations, which also allow us to explore the effect of different substrate characteristics on the thermal readout. Finally, we built a demonstrator comprising a QR Code invisible to the naked eye, which became visible in thermal images under NIR radiation. The high transparency of the printed ink and the high speed of the thermal reading (figures appear/disappear in less than 1 s) offer an extremely promising strategy toward low-cost, scalable production of photothermally active invisible labels.

One-step functionalization of mildly and strongly reduced graphene oxide with maleimide: an experimental and theoretical investigation of the Diels-Alder [4+2] cycloaddition reaction.

For large-scale graphene applications, such as the production of polymer-graphene nanocomposites, exfoliated graphene oxide (GO) and its reduced form (rGO) are presently considered to be very suitable starting materials, showing enhanced chemical reactivity with respect to pristine graphene, in addition to suitable electronic properties (i.e., tunable band gap). Among other chemical processes, a suitable way to obtain surface decoration of graphene is through a direct one-step Diels-Alder (DA) reaction, e.g. through the use of dienophile or diene moieties. However, the feasibility and extent of decoration largely depends on the specific graphene microstructure that in the case of rGO sheets is not easy to control and generally presents a high degree of inhomogeneity owing to various on-plane functionalization (e.g., epoxide and hydroxyl groups) or in-plane lattice defects. In an effort to gain some insights into the covalent functionalization of variably reduced GO samples, we present a combined experimental and theoretical study on the DA cycloaddition reaction of maleimide, a dienophile functional unit well-suited for chemical conjugation of polymers and macromolecules. In particular, we considered both mildly and strongly reduced GOs. Using thermogravimetry, Raman and X-Ray photoelectron spectroscopy, and elemental analysis we show evidence of variable chemical reactivity of rGO as a function of the residual oxygen content. Moreover, from quantum mechanical calculations carried out at the DFT level on different graphene reaction sites, we provide a more detailed molecular view to interpret experimental findings and to assess the reactivity series of different graphene modifications.

Mesoporous Bioactive Glasses in Cancer Diagnosis and Therapy: Stimuli-Responsive, Toxicity, Immunogenicity, and Clinical Translation.

Cancer is one of the top life-threatening dangers to the human survival, accounting for over 10 million deaths per year. Bioactive glasses have developed dramatically since their discovery 50 years ago, with applications that include therapeutics as well as diagnostics. A new system within the bioactive glass family, mesoporous bioactive glasses (MBGs), has evolved into a multifunctional platform, thanks to MBGs easy-to-functionalize nature and tailorable textural properties-surface area, pore size, and pore volume. Although MBGs have yet to meet their potential in tumor treatment and imaging in practice, recently research has shed light on the distinguished MBGs capabilities as promising theranostic systems for cancer imaging and therapy. This review presents research progress in the field of MBG applications in cancer diagnosis and therapy, including synthesis of MBGs, mechanistic overview of MBGs application in tumor diagnosis and drug monitoring, applications of MBGs in cancer therapy ( particularly, targeted delivery and stimuli-responsive nanoplatforms), and immunological profile of MBG-based nanodevices in reference to the development of novel cancer therapeutics.

Continuous wave vertical emission from terahertz microcavity lasers with a dual injection scheme.

Quantum cascade lasers (QCLs) represent a most promising compact source at terahertz (THz) frequencies, but efficiency of their continuous wave (CW) operation still needs to be improved to achieve large-scale exploitation. Here, we demonstrate highly efficient operation of a subwavelength microcavity laser consisting of two evanescently coupled whispering gallery microdisk resonators. Exploiting a dual injection scheme for the laser cavity, single mode CW vertical emission at 3.3 THz is obtained at 10 K with 6.4 mA threshold current and 145 mW/A slope efficiency up to 320 µW emitted power measured in quasi-CW mode. The tuning of the laser emission directionality is also obtained by independently varying the pumping strength between the microdisks. By connecting the resonators through a suspended gold bridge, the laser out-coupling efficiency in the vertical direction is strongly enhanced. Owing to the high brightness, low-power consumption and CW operation, the proposed microcavity laser design could allow the realization of high-performance CW THz QCLs ready for massive parallelization.

A sub-150-nanometre-thick and ultraconformable solution-processed all-organic transistor.

Recent advancements in the field of electronics have paved the way to the development of new applications, such as tattoo electronics, where the employment of ultraconformable devices is required, typically achievable with a significant reduction in their total thickness. Organic materials can be considered enablers, owing to the possibility of depositing films with thicknesses at the nanometric scale, even from solution. However, available processes do not allow obtaining devices with thicknesses below hundreds of nanometres, thus setting a limit. Here, we show an all-organic field effect transistor that is less than 150 nm thick and that is fabricated through a fully solution-based approach. Such unprecedented thickness permits the device to conformally adhere onto nonplanar surfaces, such as human skin, and to be bent to a radius lower than 1 µm, thereby overcoming another limitation for field-effect transistors and representing a fundamental advancement in the field of ultrathin and tattoo electronics.

A Simple Approach for Flexible and Stretchable Anti-icing Lubricant-Infused Tape.

Unwanted icing has major safety and economic repercussions on human activities, affecting means of transportation, infrastructures, and consumer goods. Compared to the common deicing methods in use today, intrinsically icephobic surfaces can decrease ice accumulation and formation without any active intervention from humans or machines. However, such systems often require complex fabrication methods and can be costly, which limits their applicability. In this study, we report the preparation and characterization of several slippery lubricant-infused porous surfaces (SLIPSs) realized by impregnating with silicone oil a candle soot layer deposited on double-sided adhesive tape. Despite the use of common household items, these SLIPSs showed anti-icing performance comparable to other systems described in the literature (ice adhesion < 20 kPa) and a good resistance to mechanical and environmental damages in laboratory conditions. The use of a flexible and functional substrate as tape allowed these devices to be stretchable without suffering significant degradation and highlights how these systems can be easily prepared and applied anywhere needed. In addition, the possibility of deforming the substrate can "allow" the application of SLIPS technology in mechanical ice removal methodologies, drastically incrementing their performance.

Endocytosis of abiotic nanomaterials and nanobiovectors: Inhibition of membrane trafficking.

Humans are exposed to nanoscopical nanobiovectors (e.g. coronavirus SARS-CoV-2) as well as abiotic metal/carbon-based nanomaterials that enter cells serendipitously or intentionally. Understanding the interactions of cell membranes with these abiotic and biotic nanostructures will facilitate scientists to design better functional nanomaterials for biomedical applications. Such knowledge will also provide important clues for the control of viral infections and the treatment of virus-induced infectious diseases. In the present review, the mechanisms of endocytosis are reviewed in the context of how nanomaterials are uptaken into cells. This is followed by a detailed discussion of the attributes of man-made nanomaterials (e.g. size, shape, surface functional groups and elasticity) that affect endocytosis, as well as the different human cell types that participate in the endocytosis of nanomaterials. Readers are then introduced to the concept of viruses as nature-derived nanoparticles. The mechanisms in which different classes of viruses interact with various cell types to gain entry into the human body are reviewed with examples published over the last five years. These basic tenets will enable the avid reader to design advanced drug delivery and gene transfer nanoplatforms that harness the knowledge acquired from endocytosis to improve their biomedical efficacy. The review winds up with a discussion on the hurdles to be addressed in mimicking the natural mechanisms of endocytosis in nanomaterials design.

Engineering Microneedle Patches for Improved Penetration: Analysis, Skin Models and Factors Affecting Needle Insertion.

Transdermal microneedle (MN) patches are a promising tool used to transport a wide variety of active compounds into the skin. To serve as a substitute for common hypodermic needles, MNs must pierce the human stratum corneum (~ 10 to 20 µm), without rupturing or bending during penetration. This ensures that the cargo is released at the predetermined place and time. Therefore, the ability of MN patches to sufficiently pierce the skin is a crucial requirement. In the current review, the pain signal and its management during application of MNs and typical hypodermic needles are presented and compared. This is followed by a discussion on mechanical analysis and skin models used for insertion tests before application to clinical practice. Factors that affect insertion (e.g., geometry, material composition and cross-linking of MNs), along with recent advancements in developed strategies (e.g., insertion responsive patches and 3D printed biomimetic MNs using two-photon lithography) to improve the skin penetration are highlighted to provide a backdrop for future research.