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This work studied the influence of the pore size and morphology of the mesoporous silica as support for formate dehydrogenase (FDH), the first enzyme of a multi-enzymatic cascade system to produce methanol, which catalyzes the reduction of carbon dioxide to formic acid. Specifically, a set of mesoporous silicas was modified with glyoxyl groups to immobilize covalently the FDH obtained from Candida boidinii. Three types of mesoporous silicas with different textural properties were synthesized and used as supports: i) SBA-15 (DP = 4 nm); ii) MCF with 0.5 wt% mesitylene/pluronic ratio (DP = 20 nm) and iii) MCF with 0.75 wt% mesitylene/pluronic ratio (DP = 25 nm). As a whole, the immobilized FDH on MCF0.75 exhibited higher thermal stability than the free enzyme, with 75% of residual activity after 24 h at 50 °C. FDH/MCF0.5 exhibited the best immobilization yields: 69.4% of the enzyme supplied was covalently bound to the support. Interestingly, the specific activity increased as a function of the pore size of support and then the FDH/MCF0.75 exhibited the highest specific activity (namely, 1.05 IU/gMCF0.75) with an immobilization yield of 52.1%. Furthermore, it was noted that the immobilization yield and the specific activity of the FDH/MCF0.75 varied as a function of the supported enzyme: as the enzyme loading increased the immobilization yield decreased while the specific activity increased. Finally, the reuse test has been carried out, and a residual activity greater than 70% was found after 5 cycles of reaction.

Background Acute Kidney Injury (AKI), a frequent complication of pateints in the Intensive Care Unit (ICU), is associated with a high mortality rate. Early prediction of AKI is essential in order to trigger the use of preventive care actions. Methods The aim of this study was to ascertain the accuracy of two mathematical analysis models in obtaining a predictive score for AKI development. A deep learning model based on a urine output trends was compared with a logistic regression analysis for AKI prediction in stages 2 and 3 (defined as the simultaneous increase of serum creatinine and decrease of urine output, according to the Acute Kidney Injury Network (AKIN) guidelines). Two retrospective datasets including 35,573 ICU patients were analyzed. Urine output data were used to train and test the logistic regression and the deep learning model. Results The deep learning model defined an area under the curve (AUC) of 0.89 (± 0.01), sensitivity = 0.8 and specificity = 0.84, which was higher than the logistic regression analysis. The deep learning model was able to predict 88% of AKI cases more than 12 h before their onset: for every 6 patients identified as being at risk of AKI by the deep learning model, 5 experienced the event. On the contrary, for every 12 patients not considered to be at risk by the model, 2 developed AKI. Conclusion In conclusion, by using urine output trends, deep learning analysis was able to predict AKI episodes more than 12 h in advance, and with a higher accuracy than the classical urine output thresholds. We suggest that this algorithm could be integrated in the ICU setting to better manage, and potentially prevent, AKI episodes. Graphic abstract

In this paper, the great sensitivity and selectivity to NO2 detection at low temperature down to ppb level of zinc oxide (ZnO) thick-film sensors are reported. Sensor performances of ZnO films prepared by screen-printing technique were evaluated comparing two different ZnO nano-powders in wurtzite crystal structure. Powders were synthesized by hydrothermal route (HT-ZnO) and by auto-combustion sol–gel synthesis (AC-ZnO). After proper characterization of the nano-powders, the thick-film sensors were fabricated by screen-printing technique onto α-alumina substrates equipped with Pt interdigitated electrodes, followed by a thermal treatment. The sensor response was studied in the range 50–250 °C. Best results were reached at 150 °C, with sensor response R (Zg/Z0)—defined as the ratio between impedance under NO2 (Zg) and impedance under dry air (Z0)—equal to 42.92 for HT-ZnO and to 23.18 for AC-ZnO under 0.5 ppm of NO2 in dry conditions. Finally, response and recovery time were measured, and selectivity of the sensors was determined by exposing the film toward O3, CO2, CH4, N2O and humidity at the best working temperature. Both sensors showed great sensitivity for NO2 detection, supporting the exploitation of these sensors as NO2 detectors at ppb level.

In this work, it is proposed an environmental friendly sonophotocatalytic approach to efficiently treat polluted waters from industrial dyes exploiting ZnO micro- and nano-materials. For the first time, we deeply investigated the generation of reactive oxygen species (ROS) under ultrasound stimulation of different ZnO structures by Electron Paramagnetic Resonance Spectroscopy (EPR). Indeed, five zinc oxide (ZnO) micro- and nano-structures, i.e. Desert Roses (DRs), Multipods (MPs), Microwires (MWs), Nanoparticles (NPs) and Nanowires (NWs), were studied for the Rhodamine B (RhB) sonodegradation under ultrasonic irradiation. The DRs microparticles demonstrated the best sonocatalytic performance (100% degradation of RhB in 180 min) and the highest OH· radicals generation under ultrasonic irradiation. Strikingly, the coupling of ultrasound and sun-light irradiation in a sonophotodegradation approach led to 100% degradation efficiency, i.e. color reduction, of RhB in just 10 min, revealing a great positive synergy between the photocatalytic and sonocatalytic mechanisms. The RhB sonophotocatalytic degradation was also evaluated at different initial dye concentrations and with the presence of anions in solution. It was demonstrated a good stability over repeated cycles of dye treatment, which probe the applicability of this technique with industrial effluents. In conclusion, sonophotocatalytic degradation synergizing sunlight and ultrasound in the presence of DRs microparticles shows a great potential and a starting point to investigate further the efficient treatment of organic dyes in wastewater.

Nanomedicine is an emerging treatment approach for many cancers, characterized by having high sensitivity and selectivity for tumor cells and minimal toxic effects induced by the conventional chemotherapeutics. In these context, smart nanoparticles (NPs) are getting increasingly relevant in the development of new therapies. NPs with specific chemical composition and/or structure and being stimuli-responsive to magnetic, light or ultrasound waves are new promising tools. In the present work, amorphous-titania propyl-amine functionalized (a-TiO2-NH2) NPs, coated with bovine serum albumin (BSA), are stimulated with high energy shock waves to induce cytotoxic effects in cancer cells. First, a new method to coat a-TiO2-NH2 NPs with BSA (a-TiO2-NH2/BSA) was proposed, allowing for a high dispersion and colloidal stability in a cell culture media. The a-TiO2-NH2/BSA NPs showed no cancer cell cytotoxicity. In a second step, the use of shock waves to stimulate a-TiO2-NH2/BSA NPs, was evaluated and optimized. A systematic study was performed in in vitro cell culture aiming to impair the cancer cell viability: NP concentrations, time steps and single versus multiple shock waves treatments were studied. The obtained results highlighted the relevance of NPs design and administration time point with respect to the shock wave treatment and allow to hypothesize mechanical damages to cells.

Simple Summary In recent years, immunotherapy has shown great advancement, becoming a powerful tool to combat cancer. In this context, the use of biologically derived vesicles has also acquired importance for cancer immunotherapy. Extracellular vesicles are thus proposed to transport molecules able to trigger an immune response and thus fight cancer cells. As a particular immunotherapeutic approach, a new technique also consists in the exploitation of extracellular vesicles as new cancer vaccines. The present review provides basic notions on cancer immunotherapy and describes several clinical trials in which therapeutic anticancer vaccines are tested. In particular, the potential of extracellular vesicles-based therapeutic vaccines in the treatment of cancer patients is highlighted, even with advanced stage-cancer. A focus on the clinical studies, already completed or still in progress, is offered and a systematic collection and reorganization of the present literature on this topic is proposed to the reader. Abstract Extracellular vesicles (EVs) are natural particles formed by the lipid bilayer and released from almost all cell types to the extracellular environment both under physiological conditions and in presence of a disease. EVs are involved in many biological processes including intercellular communication, acting as natural carriers in the transfer of various biomolecules such as DNA, various RNA types, proteins and different phospholipids. Thanks to their transfer and targeting abilities, they can be employed in drug and gene delivery and have been proposed for the treatment of different diseases, including cancer. Recently, the use of EVs as biological carriers has also been extended to cancer immunotherapy. This new technique of cancer treatment involves the use of EVs to transport molecules capable of triggering an immune response to damage cancer cells. Several studies have analyzed the possibility of using EVs in new cancer vaccines, which represent a particular form of immunotherapy. In the literature there are only few publications that systematically group and collectively discuss these studies. Therefore, the purpose of this review is to illustrate and give a partial reorganization to what has been produced in the literature so far. We provide basic notions on cancer immunotherapy and describe some clinical trials in which therapeutic cancer vaccines are tested. We thus focus attention on the potential of EV-based therapeutic vaccines in the treatment of cancer patients, overviewing the clinically relevant trials, completed or still in progress, which open up new perspectives in the fight against cancer.

This work reports the study of ZnO-based anodes for the photoelectrochemical regeneration of the oxidized form of nicotinamide adenine dinucleotide (NAD+). The latter is the most important coenzyme for dehydrogenases. However, the high costs of NAD+ limit the use of such enzymes at the industrial level. The influence of the ZnO morphologies (flower-like, porous film, and nanowires), showing different surface area and crystallinity, was studied. The detection of diluted solutions (0.1 mM) of the reduced form of the coenzyme (NADH) was accomplished by the flower-like and the porous films, whereas concentrations greater than 20 mM were needed for the detection of NADH with nanowire-shaped ZnO-based electrodes. The photocatalytic activity of ZnO was reduced at increasing concentrations of NAD+ because part of the ultraviolet irradiation was absorbed by the coenzyme, reducing the photons available for the ZnO material. The higher electrochemical surface area of the flower-like film makes it suitable for the regeneration reaction. The illumination of the electrodes led to a significant increase on the NAD+ regeneration with respect to both the electrochemical oxidation in dark and the only photochemical reaction. The tests with formate dehydrogenase demonstrated that 94% of the regenerated NAD+ was enzymatically active.

In recent years, zinc oxide (ZnO)-based nanomaterials have attracted a great deal of interest thanks to their outstanding and multifunctional properties [...]

In the last decades, liposomes acquired a striking success in the biomedical field thanks to their biocompatibility and drug delivery ability. Many liposomal drug formulations have been already approved by the Food and Drug Administration (FDA) and used for the treatment of a wide range of pathologies with or without further engineering. Their clinical application requires strict compliance with high standard quality rules, and it is crucial to employ storage methods that do not affect the integrity of the vesicles and preventing the leakage of their cargo. In this work, the design of a suitable formulation for freeze-drying had been investigated for two different liposomes, DOPC-DOTAP and the PEGylated counterpart, DOPC-DOTAP-DSPE-PEG. The role of various cryoprotectants was evaluated paying attention to their ability to preserve the structural integrity of liposomes. At first, the study was focused on freezing and two methodologies were investigated, quenching in liquid nitrogen and shelf-ramped freezing. This analysis showed that the disaccharides (cellobiose, glucose, lactose, sucrose, and trehalose) and the polyol (mannitol) protected successfully the integrity of liposomes, while during the process, in the presence of a surfactant, liposomes were strongly damaged and fragmented by the ice crystals. Furthermore, the choice of the rate of freezing depended on the different compositions of the lipid bilayer. Finally, the effects of lyophilization on liposomes with and without additives were studied; cellobiose, lactose and trehalose showed encouraging results for the maintenance of the morpho-functional parameters of liposomes during the entire freeze-drying process.

The discovery of isocitrate dehydrogenases (IDHs) mutations in several malignancies has brought to the approval of drugs targeting IDH1/2 mutants in cancers. More recently it has been suggested that the enzymatic inhibition of IDHs may have therapeutic potentials also for wild-type IDH cancers. Specifically, IDH2 inhibition can sensitize multiple myeloma cells to proteasome inhibitors. However, inhibitors directed against native IDHs are not present on the market. Here, we exploited an allosteric inhibitor of mutant IDH2 (AGI-6780), known to also decrease the activity of wild-type IDH2. Since AGI-6780 effectiveness in vivo is limited by its high hydrophobicity and very low bioavailability, the drug was loaded into mesoporous silica nanoparticles (MSNs) with the aim to enhance its efficacy. Furthermore, to enable high drug retention into the silica pores, improve biocompatibility, and reduce the off-target delivery of the drug, a Supported phosphoLipidic Bilayer (SLB) was self-assembled on the outer MSN surface. The silica nanoparticles were thus coated with three different lipid formulations and characterized in terms of structure, size, and morphology. We demonstrated that MSN@SLB nanoparticles have improved colloidal stability and hemocompatibility with respect to pristine MSN. We showed that MSN@SLB formulation displays an excellent loading and retention of the IDH2 inhibitor AGI-6780, with a limited drug leakage depending on the lipid formulation. Finally, we proved that AGI-6780-loaded MSN@SLB nanoparticles efficaciously inhibited the IDH2 enzymatic activity of multiple myeloma cells. Overall, this study provides a proof of concept of drug delivery to multiple myeloma cells by repurposing a neglected/dismissed drug (AGI-6780) with the use of smart nanoparticles and enabling the sensitization of multiple myeloma cells towards other possible treatments.

Pandemics are enormous threats to the world that impact all aspects of our lives, especially the global economy. The COVID-19 pandemic has emerged since December 2019 and has affected the global economy in many ways. As the world becomes more interconnected, the economic impacts of the pandemic become more serious. In addition to increased health expenditures and reduced labor force, the pandemic has hit the supply and demand chain massively and caused trouble for manufacturers who have to fire some of their employees or delay their economic activities to prevent more loss. With the closure of manufacturers and companies and reduced travel rates, usage of oil after the beginning of the pandemic has decreased significantly that was unprecedented in the last 30 years. The mining industry is a critical sector in several developing countries, and the COVID-19 pandemic has hit this industry too. Also, world stock markets declined as investors started to become concerned about the economic impacts of the COVID-19 pandemic. The tourism industry and airlines have also experienced an enormous loss too. The GDP has reduced, and this pandemic will cost the world more than 2 trillion at the end of 2020.

Zinc oxide nanoparticles (ZnO NPs) are currently among the most promising nanomaterials for theranostics. However, they suffer from some drawbacks that could prevent their application in nanomedicine as theranostic agents. The doping of ZnO NPs can be effectively exploited to enhance the already-existing ZnO properties and introduce completely new functionalities in the doped material. Herein, we propose a novel synthetic approach for iron-doped ZnO (Fe:ZnO) NPs as a multifunctional theranostic nanoplatform aimed at cancer cell treatment. Pure ZnO and Fe:ZnO NPs, with two different levels of iron doping, were synthesized by a rapid wet-chemical method and analyzed in terms of morphology, crystal structure and chemical composition. Interestingly, Fe:ZnO NPs featured bioimaging potentialities thanks to superior optical properties and novel magnetic responsiveness. Moreover, iron doping provides a way to enhance the electromechanical behavior of the NPs, which are then expected to show enhanced therapeutic functionalities. Finally, the intrinsic therapeutic potentialities of the NPs were tested in terms of cytotoxicity and cellular uptake with both healthy B lymphocytes and cancerous Burkitt’s lymphoma cells. Furthermore, their biocompatibility was tested with a pancreatic ductal adenocarcinoma cell line (BxPC-3), where the novel properties of the proposed iron-doped ZnO NPs can be potentially exploited for theranostics.

Conventional therapies to treat cancer often exhibit low specificity, reducing the efficiency of the treatment and promoting strong side effects. To overcome these drawbacks, new ways to fight cancer cells have been developed so far focusing on nanosystems. Different action mechanisms to fight cancer cells have been explored using nanomaterials, being their remote activation one of the most promising. Photo- and sonodynamic therapies are relatively new approaches that emerged following this idea. These therapies are based on the ability of specific agents to generate highly cytotoxic reactive oxygen species (ROS) by external stimulation with light or ultrasounds (US), respectively. Crystalline (TiO2) and amorphous titania (a-TiO2) nanoparticles (NPs) present a set of very interesting characteristics, such as their photo-reactivity, photo stability, and effective bactericidal properties. Their production is inexpensive and easily scalable, they are reusable and demonstrated already to be nontoxic. Therefore, these NPs have been increasingly studied as promising photo- or sonosensitizers to be applied in photodynamic/sonodynamic therapies in the future. However, they suffer from poor colloidal stability in aqueous and biological relevant media. Therefore, various organic and polymer-based coatings have been proposed. In this work, the role of a-TiO2 based NPs synthesized through a novel, room-temperature, base-catalyzed, sol-gel protocol in the generation of ROS and as an enhancer of acoustic inertial cavitation was evaluated under ultrasound irradiation. A novel biomimetic coating based on double lipidic bilayer, self-assembled on the a-TiO2-propylamine NPs, is proposed to better stabilize them in water media. The obtained results show that the biomimetic a-TiO2-propylamine NPs are promising candidates to be US responding agents, since an improvement of the cavitation effect occurs in presence of the developed NPs. Further studies will show their efficacy against cancer cells.

Highlights The present review highlights the importance of remotely activated nanoparticles for anticancer purposes.For each physical input, we present its possible active synergy with several nanomaterials.We report examples and the mechanism of action when clarified.Clinical trials involving remotely triggered nanoparticles are discussed., Cancer has nowadays become one of the leading causes of death worldwide. Conventional anticancer approaches are associated with different limitations. Therefore, innovative methodologies are being investigated, and several researchers propose the use of remotely activated nanoparticles to trigger cancer cell death. The idea is to conjugate two different components, i.e., an external physical input and nanoparticles. Both are given in a harmless dose that once combined together act synergistically to therapeutically treat the cell or tissue of interest, thus also limiting the negative outcomes for the surrounding tissues. Tuning both the properties of the nanomaterial and the involved triggering stimulus, it is possible furthermore to achieve not only a therapeutic effect, but also a powerful platform for imaging at the same time, obtaining a nano-theranostic application. In the present review, we highlight the role of nanoparticles as therapeutic or theranostic tools, thus excluding the cases where a molecular drug is activated. We thus present many examples where the highly cytotoxic power only derives from the active interaction between different physical inputs and nanoparticles. We perform a special focus on mechanical waves responding nanoparticles, in which remotely activated nanoparticles directly become therapeutic agents without the need of the administration of chemotherapeutics or sonosensitizing drugs.

In the last 30 years the research about the zinc oxide nanoparticles (ZnO NPs) and related toxicity had a boom. ZnO NPs show cytotoxicity for both prokaryotic and eukaryotic cells and many studies demonstrated a selective toxicity towards cancer cells. However, with the increasing number of publications, we assisted to an increase in the discrepancies between the various results obtained. Soon the scientific community understood that the ZnO NCs toxicity behaviour is affected by many factors, related not only to the ZnO NPs themselves, but also to the experimental conditions used. Many recent reviews discuss about these parameters reporting experimental evidences and try to assess general statements about the ZnO NPs cytotoxicity. These informations are extremely useful for the evaluation of which type of ZnO NPs is more or less suitable for a specific study or application. However, despite that, a deep comprehension of the ZnO NPs behaviour in relation to the different experimental conditions is still lacking. Actually, a full understanding of the reasons behind the NPs behaviour is essential to better assess their biological activity and in particular their therapeutic application, avoiding undesired effects both in the experimental and clinical contexts. This tutorial review aims to be an experimental and practical guide for scientists that face with the use of ZnO NPs for biomedical applications and, in particular, for their therapeutic purposes. The driving idea is to not simply resume the results obtained in the literature, but to provide the instruments for a deep comprehension of the mechanisms affecting the ZnO NPs cytotoxicity and behavior. This review also aims to point out the attention on the critical experimental parameters to be considered when working with these NPs, underlying the main related risks and limitations that the scientists have to face.

Extracellular vesicles (EVs) are natural carriers produced by many different cell types that have a plethora of functions and roles that are still under discovery. This review aims to be a compendium on the current advancement in terms of EV modifications and re-engineering, as well as their potential use in nanomedicine. In particular, the latest advancements on artificial EVs are discussed, with these being the frontier of nanomedicine-based therapeutics. The first part of this review gives an overview of the EVs naturally produced by cells and their extraction methods, focusing on the possibility to use them to carry desired cargo. The main issues for the production of the EV-based carriers are addressed, and several examples of the techniques used to upload the cargo are provided. The second part focuses on the engineered EVs, obtained through surface modification, both using direct and indirect methods, i.e., engineering of the parental cells. Several examples of the current literature are proposed to show the broad variety of engineered EVs produced thus far. In particular, we also report the possibility to engineer the parental cells to produce cargo-loaded EVs or EVs displaying specific surface markers. The third and last part focuses on the most recent advancements based on synthetic and chimeric EVs and the methods for their production. Both top-down or bottom-up techniques are analyzed, with many examples of applications.

Smart nanoparticles for medical applications have gathered considerable attention due to an improved biocompatibility and multifunctional properties useful in several applications, including advanced drug delivery systems, nanotheranostics and in vivo imaging. Among nanomaterials, zinc oxide nanoparticles (ZnO NPs) were deeply investigated due to their peculiar physical and chemical properties. The large surface to volume ratio, coupled with a reduced size, antimicrobial activity, photocatalytic and semiconducting properties, allowed the use of ZnO NPs as anticancer drugs in new generation physical therapies, nanoantibiotics and osteoinductive agents for bone tissue regeneration. However, ZnO NPs also show a limited stability in biological environments and unpredictable cytotoxic effects thereof. To overcome the abovementioned limitations and further extend the use of ZnO NPs in nanomedicine, doping seems to represent a promising solution. This review covers the main achievements in the use of doped ZnO NPs for nanomedicine applications. Sol-gel, as well as hydrothermal and combustion methods are largely employed to prepare ZnO NPs doped with rare earth and transition metal elements. For both dopant typologies, biomedical applications were demonstrated, such as enhanced antimicrobial activities and contrast imaging properties, along with an improved biocompatibility and stability of the colloidal ZnO NPs in biological media. The obtained results confirm that the doping of ZnO NPs represents a valuable tool to improve the corresponding biomedical properties with respect to the undoped counterpart, and also suggest that a new application of ZnO NPs in nanomedicine can be envisioned.

The discovery of novel catalytic materials showing unprecedented properties and improved functionalities represents a major challenge to design advanced oxidation processes for wastewater purification. In this work, antimony (Sb) doping is proposed as a powerful approach for enhancing the photo- and piezocatalytic performances of piezoelectric zinc oxide (ZnO) thin films. To investigate the role played by the dopant, the degradation of Rhodamine-β (Rh-β), a dye pollutant widely present in natural water sources, is studied when the catalyst is irradiated by ultraviolet (UV) light or ultrasound (US) waves. Depending on the doping level, the structural, optical, and ferroelectric properties of the catalyst can be properly set to maximize the dye degradation efficiency. Independently of the irradiation source, the fastest and complete dye degradation is observed in the presence of the doped catalyst and for an optimal amount of the inserted dopant. Among ZnO:Sb samples, the most doped one (5 at. %) shows improved UV light absorption and photocatalytic properties. Conversely, the piezocatalytic efficiency is maximized using the lowest Sb amount (1 at. %). The superior ferroelectric polarization observed in this case highly favors the adsorption of electrically charged species, in particular of the dye in the protonated form (Rh-β+) and of OH-, to the catalyst surface and the production of hydroxyl radicals responsible for dye degradation.

Drug delivery systems aim at a reduction of side effects in chemotherapy. This is achieved by encapsulation of drugs in nanocarriers followed by controlled release of these drugs at the site of the diseased tissue. Though inorganic or polymeric nanoparticles (NPs) are often used as nanocarriers,(1, 2) hybrid nanomaterials such as metal−organic framework (MOF) NPs have recently emerged as a valuable alternative.(3-6) They are synthesized from inorganic and organic building block units to create porous three-dimensional frameworks. Because of this building principle, the composition and structure of these materials are highly tunable.(7-10) Furthermore, both external and internal surfaces can be functionalized independently. With these properties, MOF NPs can be designed to fit the specific requirements of the desired application.(3, 11) For drug delivery purposes these so-called “design materials” have been synthesized with high porosity allowing for high drug loading capacities. They also have been designed to be biodegradable. Specifically, iron-based MOF NPs have attracted great attention. In addition to the above-mentioned properties, they can be detected via magnetic resonance imaging (MRI), rendering them an ideal platform for theranostics.(12-14) In our study, we focus on one of these iron-based MOFs, namely MIL-88A NPs, which are composed of iron(III) and fumaric acid.(15, 16) Both compounds can be found in the body and the NPs are reported to be nontoxic.(12) Additionally, MIL-88A NPs have been shown to efficiently host chemotherapeutic drugs.(12) Thus, they represent a promising nanocarrier.

We would like to thank Prof. Raif Geha, the James L. Gamble Professor of Pediatrics at the Harvard Medical School and Chief of the Division of Immunol‑ ogy, Allergy, and Rheumatology at Boston Children’s Hospital, for his critical comments on this paper., The COVID-19 pandemic has become the leading societal concern. The pandemic has shown that the public health concern is not only a medical problem, but also afects society as a whole; so, it has also become the leading scientifc concern. We discuss in this treatise the importance of bringing the world’s scientists together to fnd efective solu‑ tions for controlling the pandemic. By applying novel research frameworks, interdisciplinary collaboration promises to manage the pandemic’s consequences and prevent recurrences of similar pandemics.

Oxidative stress represents a common issue in most neurological diseases, causing severe impairments of neuronal cell physiological activity that ultimately lead to neuron loss of function and cellular death. In this work, lipid-coated polydopamine nanoparticles (L-PDNPs) are proposed both as antioxidant and neuroprotective agents, and as a photothermal conversion platform able to stimulate neuronal activity. L-PDNPs showed the ability to counteract reactive oxygen species (ROS) accumulation in differentiated SH-SY5Y, prevented mitochondrial ROS-induced dysfunctions and stimulated neurite outgrowth. Moreover, for the first time in the literature, the photothermal conversion capacity of L-PDNPs was used to increase the intracellular temperature of neuron-like cells through near-infrared (NIR) laser stimulation, and this phenomenon was thoroughly investigated using a fluorescent temperature-sensitive dye and modeled from a mathematical point of view. It was also demonstrated that the increment in temperature caused by the NIR stimulation of L-PDNPs was able to produce a Ca2+ influx in differentiated SH-SY5Y, being, to the best of our knowledge, the first example of organic nanostructures used in such an approach. This work could pave the way to new and exciting applications of polydopamine-based and of other NIR-responsive antioxidant nanomaterials in neuronal research.

Fast diagnosis and more efficient therapies for cancer surely represent one of the huge tasks for the worldwide researchers’ and clinicians’ community. In the last two decades, our understanding of the biology and molecular pathology of cancer mechanisms, coupled with the continuous development of the material science and technological compounds, have successfully improved nanomedicine applications in oncology. This review argues on nanomedicine application of engineered extracellular vesicles (EVs) in oncology. All the most innovative processes of EVs engineering are discussed together with the related degree of applicability for each one of them in cancer nanomedicines.

Ion homeostasis is essential for cellular survival, and elevated concentrations of specific ions are used to start distinct forms of programmed cell death. However, investigating the influence of certain ions on cells in a controlled way has been hampered due to the tight regulation of ion import by cells. Here, it is shown that lipid-coated iron-based metal-organic framework nanoparticles are able to deliver and release high amounts of iron ions into cells. While high concentrations of iron often trigger ferroptosis, here, the released iron induces pyroptosis, a form of cell death involving the immune system. The iron release occurs only in slightly acidic extracellular environments restricting cell death to cells in acidic microenvironments and allowing for external control. The release mechanism is based on endocytosis facilitated by the lipid-coating followed by degradation of the nanoparticle in the lysosome via cysteine-mediated reduction, which is enhanced in slightly acidic extracellular environment. Thus, a new functionality of hybrid nanoparticles is demonstrated, which uses their nanoarchitecture to facilitate controlled ion delivery into cells. Based on the selectivity for acidic microenvironments, the described nanoparticles may also be used for immunotherapy: the nanoparticles may directly affect the primary tumor and the induced pyroptosis activates the immune system.

Three different single-lumen double-J ureteral stents of different materials were studied and compared after the insertion into a dynamic in vitro model with sterile artificial urine up to 6 months. The aim was to evaluate, at selected time steps of 1, 3, and 6 months, the material performances of the stents in preventing the formation of inorganic encrustations. Morphological, compositional, and qualitative analyses were carried out both before stent insertion and after stent permanence for the different time steps, showing an increasing level of encrustation which remains particularly low in the case of two polyurethane stents. Mechanical tests show that both the polyurethane stents and the chitosan one do not decrease the tensile strength after 6 months of indwelling. Evaluation of the wetting behavior of the stent outer surfaces indicates a hydrophilic behavior in most of the cases, which is generally preserved after immersion in artificial urine for the different time steps. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 2244-2253, 2017.

Mesoporous materials, especially those made of silica or silicon, are capturing great interest in the field of nanomedicine [...]

Nanoparticles able to promote inertial cavitation when exposed to focused ultrasound have recently gained much attention due to their vast range of possible applications in the biomedical field, such as enhancing drug penetration in tumor or supporting ultrasound contrast imaging. Due to their nanometric size, these contrast agents could penetrate through the endothelial cells of the vasculature to target tissues, thus enabling higher imaging resolutions than commercial gas-filled microbubbles. Herein, Zinc Oxide NanoCrystals (ZnO NCs), opportunely functionalized with amino-propyl groups, are developed as novel nanoscale contrast agents that are able, for the first time, to induce a repeatedly and over-time sustained inertial cavitation as well as ultrasound contrast imaging. The mechanism behind this phenomenon is investigated, revealing that re-adsorption of air gas nanobubbles on the nanocrystal surface is the key factor for this re-chargeable cavitation. Moreover, inertial cavitation and significant echographic signals are obtained at physiologically relevant ultrasound conditions (MI 1.9), showing great potential for low side-effects in in-vivo applications of the novel nanoscale agent from diagnostic imaging to gas-generating theranostic nanoplatforms and to drug delivery.

The presence of leaky vasculature and the lack of lymphatic drainage of small structures by the solid tumors formulate nanoparticles as promising delivery vehicles in cancer therapy. In particular, among various nanoparticles, the mesoporous silica nanoparticles (MSN) exhibit numerous outstanding features, including mechanical thermal and chemical stability, huge surface area and ordered porous interior to store different anti-cancer therapeutics with high loading capacity and tunable release mechanisms. Furthermore, one can easily decorate the surface of MSN by attaching ligands for active targeting specifically to the cancer region exploiting overexpressed receptors. The controlled release of drugs to the disease site without any leakage to healthy tissues can be achieved by employing environment responsive gatekeepers for the end-capping of MSN. To achieve precise cancer chemotherapy, the most desired delivery system should possess high loading efficiency, site-specificity and capacity of controlled release. In this review we will focus on multimodal decorations of MSN, which is the most demanding ongoing approach related to MSN application in cancer therapy. Herein, we will report about the recently tried efforts for multimodal modifications of MSN, exploiting both the active targeting and stimuli responsive behavior simultaneously, along with individual targeted delivery and stimuli responsive cancer therapy using MSN.

The use of nanomaterials in the field of bone tissue engineering implants is continuously dealing with the development of innovative solutions to common problems, as infection by colonization with common microbial agents, antibiotic bacterial resistance, and the formation of new bone tissue. Among them, ZnO nanostructures are promising candidates thanks to their intrinsic antimicrobial activity and high biocompatibility. In this paper we aim to analyse the behaviour of ZnO nanocrystals (ZnO NCs), prepared with a new synthetic approach and not embedded in any composite matrix, for bone implants applications in-vitro. In particular, we have developed a novel, fast and reproducible microwave-assisted synthesis, obtaining highly-crystalline, round-shaped ZnO NCs of 20 nm in diameter as an extremely-stable colloidal solution in ethanol. Part of them were also chemically functionalized by anchoring amino-propyl groups to the ZnO surface (ZnO-NH2 NCs). Thus, the role of both ZnO NCs concentration and surface chemistry are tested in terms of biocompatibility towards pre-osteoblasts cells, promotion of cell proliferation and differentiation, and also in terms of antimicrobial activity against Gram positive and negative bacteria, such as Escherichia coli and Staphylococcus aureus, respectively. The results propose the ZnO-NH2 NCs as the most promising candidate to solve infections disease in bone implants and promote bone tissue proliferation at the same time, even at high concentrations. Whereas further investigations are needed for example to clarify the mechanism inhibiting biofilm formation and to investigate their role in in-vivo assays, we demonstrated that a fine and reproducible control over the chemical and structural parameters in ZnO nanomaterials can open new horizons in the use of functionalized ZnO NCs as a highly biocompatible and osteoinductive nanoantibiotic agent for bone tissue engineering.

Aim The effective application of nanoparticles in cancer theranostics is jeopardized by their aggregation in biological media, rapid degradation and clearance. The design of biomimetic nanoconstructs with enhanced colloidal stability and non-immunogenicity is therefore essential. We propose naturally stable cell-derived extracellular vesicles to encapsulate zinc oxide (ZnO) nanocrystals as efficacious nanodrugs, to obtain highly biomimetic and stable Trojan nano-horses (TNHs). Materials & methods Coupling efficiency, biostability, cellular cytotoxicity and internalization were tested. Results In vitro studies showed a high internalization of TNHs into cancer cells and efficient cytotoxic activity thanks to ZnO intracellular release. Conclusion TNHs represent an efficient biomimetic platform for future nanotheranostic applications, with biomimetic extracellular vesicle-lipid envelope, facilitated ZnO cellular uptake and potential therapeutic implications., Graphic abstract

The use of porous oxide nanoparticles for diagnostic and therapeutic applications of ultrasound is growing interest owing to their unique surface properties, which can be exploited to get more sensitive and long life stable contrast agents as well as to increase radical generation through their exposure to low-intensity ultrasound, pointing out their possible applications in the oncological field, for both imaging applications and therapeutic functions. It has been largely demonstrated that the presence of porous nanoparticles (NPs) in aqueous solutions decreases the cavitation threshold. NPs are indeed able to stabilize nanobubbles on their surface and inside well-defined cavities, acting as cavitation nuclei. Here we report result the enhancement of radicals generation and lowering effect of cavitation threshold, with respect to pure water, using functionalized mesoporous silica NPs and functionalized ZnO NPs. Cavitation activity was quantified by analyzing the cavitation noise detected by a needle hydrophone and correlated with the analysis of images acquired with an ultrasound scanner probe to monitor the bubbles dynamics. These investigations were finally correlated with electron paramagnetic resonance (EPR) measurements in order to measure the enhancement of radical generation given the presence porous nanoparticles respect to water at same ultrasound intensity.

Reactive oxygen species (ROS) effects on living cells and tissues is multifaceted and their level or dose can considerably affect cell proliferation and viability. It is therefore necessary understand their role also designing ways able to regulate their amount inside cells, i.e., using engineered nanomaterials with either antioxidant properties or, for cancer therapy applications, capable to induce oxidative stress and cell death, through tunable ROS production. In this paper, we report on the use of single-crystalline zinc oxide (ZnO) round-shaped nanoparticles, yet ZnO nanocrystals (NCs) functionalized with amino-propyl groups (ZnO-NH2 NCs), combined with pulsed ultrasound (US). We show the synergistic effects produced by NC-assisted US which are able to produce different amount of ROS, as a result of inertial cavitation under the pulsed US exposure. Using Passive Cavitation Detection (PCD) and Electron Paramagnetic Resonance (EPR) spectroscopy, we systematically study which are the key parameters, monitoring, and influencing the amount of generated ROS measuring their concentration in water media and comparing all the results with pure water batches. We thus propose a ROS generation mechanism based on the selective application of US to the ZnO nanocrystals in water solutions. Ultrasound B-mode imaging is also applied, proving in respect to pure water, the enhanced ecographic signal generation of the aqueous solution containing ZnO-NH2 NCs when exposed to pulsed ultrasound. Furthermore, to evaluate the applicability of ZnO-NH2 NCs in the biomedical field, the ROS generation is studied by interposing different tissue mimicking materials, like phantoms and ex vivo tissues, between the US transducer and the sample well. As a whole, we clearly proof the enhanced capability to produce ROS and to control their amount when using ZnO-NH2 NCs in combination with pulsed ultrasound anticipating their applicability in the fields of biology and health care.

Nanotechnology, as an interdisciplinary science, combines engineering, physics, material sciences, and chemistry with the biomedicine knowhow, trying the management of a wide range of diseases. Nanoparticle-based devices holding tumor imaging, targeting and therapy capabilities are formerly under study. Since conventional hematological therapies are sometimes defined by reduced selectivity, low therapeutic efficacy and many side effects, in this review we discuss the potential advantages of the NPs' use in alternative/combined strategies. In the introduction the basic notion of nanomedicine and nanoparticles' classification are described, while in the main text nanodiagnostics, nanotherapeutics and theranostics solutions coming out from the use of a wide-ranging NPs availability are listed and discussed.

Neurodegenerative diseases comprise a large group of disorders characterized by a dramatic synaptic connections loss, occurring as a result of neurodegeneration, which is closely related to the overproduction of reactive oxygen and nitrogen species. Currently, the treatment of neurodegenerative diseases has been limited mainly because of the inability of the synthesized delivery systems to cross the blood-brain barrier and to successfully deliver their therapeutic cargo to the diseased tissue. Taking into consideration the aforementioned limitations, we designed a lipid-based nanotherapeutic vector composed of biomimetic lipids and CeO2nanoparticles (nanoceria, NC). NC have shown to be a promising tool for the treatment of several pathological conditions ranging from cancer to neurological diseases, mainly because of their antioxidant properties, while lipid-based structures have been shown to have an inherent ability to cross the blood-brain barrier. The lipid-based nanotherapeutics were successfully fabricated using a combination of ultrasonication and high-pressure homogenization techniques, and they were fully characterized morphologically and physicochemically. Their antioxidant ability was demonstrated using electron paramagnetic resonance spectroscopy and antioxidant assays. These innovative nanotherapeutics demonstrated a higher colloidal stability with respect to free NC, preserving at the same time their antioxidant properties. Finally, the ability of the lipid carriers to cross a model of the blood-brain barrier and to be internalized by neurons, acting both as neuroprotective and pro-neurogenic agents, was demonstrated using single- and triple-culture systems.

Mesoporous zinc oxide (ZnO) scaffolds coated with drop-cast graphene oxide (GO) flakes are proposed to be a novel bilayer system featuring bioactivity, biocompatibility, and promising loading/release properties for controlled drug-delivery systems. The high-surface-area ZnO scaffolds show clear apatite deposition, but their particular surface chemistry and topography prevent the formation of a continuous coating, resulting in micrometric crystalline apatite aggregates after 28 days in simulated body fluid (SBF). When gentamicin sulfate (GS) is considered as a model molecule, pure ZnO scaffolds also show functional GS loading efficiency, with fast in vitro release kinetics driven by a simple diffusion mechanism. Strikingly, the bioactivity and GS delivery properties of mesoporous ZnO are efficiently triggered by drop-casting GO flakes atop the mesoporous scaffold surface. The resulting ZnO@GO bilayer scaffolds show the formation of a uniform apatite coating after 28 days in SBF and demonstrate a biocompatible behavior, supporting the culture of SaOS-2 osteoblast-like cells. Moreover, the GO coating also leads to a barrier-layer effect, preventing fast GS release, particularly in the short time range. This barrier effect, coupled with the existence of nanopores within the GO structure, sieves drug molecules from the mesoporous ZnO matrix and allows for a delayed release of the GS molecule. We, thus, demonstrated a new-generation ZnO@GO bilayer system as effective multifunctional and biocompatible scaffold for bone tissue engineering.

High-surface-area porous coatings represent an interesting option to fabricate eluting stents with additional functionalities, as controlled drug delivery and antibacterial resistance properties. ZnO is a biocompatible material available in various high-surface-area morphologies, with promising antibacterial properties. Hydrophilic 2-hydroxyethyl methacrylate (HEMA) polymers (pHEMA) have been widely investigated for their biomedical applications, thanks to their biocompatibility, absence of toxicity, and tunable swelling properties. This work aims to demonstrate the use of porous ZnO/polymer bilayer coatings for future drug eluting stent applications. Sputtered mesoporous ZnO layers were coated with pHEMA and p(HEMA-co-acrylic acid (AA)) films through vacuum infiltration and drop-casting methods. The last approach was found to be the most suitable one for achieving a good polymer infiltration within the ZnO matrix and to avoid the mechanical detachment of the porous film from the substrate. The corresponding release properties were evaluated by loading a fluorescent dye in the host ZnO matrix, before drop-casting the polymer coating. For pure ZnO, the release of the dye was completed after 2 h. For ZnO/pHEMA, the sustained release of the molecule was achieved with only 30% released after 2 h and 100% released after seven days. In this case, the pH-triggered delivery properties were also demonstrated by switching from neutral to acidic pH conditions. No significant changes were obtained for the ZnO/p(HEMA-co-AA) system, which exhibited a faster swelling behavior and a release profile similar to pure ZnO.

ZnO nanomaterials are gaining lots of attention due to their biocompatible nature coupled with promising piezoelectric properties, envisioning a new generation of lead-free smart materials. Herein, an effective strategy to improve the piezoelectric behaviour of sputtered ZnO thin films is proposed by introducing a nanobranched porous thin film structure composed by a network of randomly-oriented wurtzite crystallites, rather than using compact ZnO thin films, considered in this work as a conventional reference for sputtered ZnO thin film structures. The nanobranched ZnO structure shows a hydrophilic behavior together with a piezoelectric output voltage of around 3 V. In comparison, compact ZnO thin films exhibit a maximum piezoelectric voltage generation below 0.8 V and a hydrophobic state. The more defective structure of the nanobranched ZnO thin films, with respect of the long-range ordered crystal structure of compact ZnO thin films, reduces free carrier concentration and mobility, thus limiting the screening potential and at the same time improving piezoelectric voltage generation. All the characterization results highlight the promising perspectives in using nanobranched ZnO thin films as novel piezoelectric materials for biosensing and tissue engineering applications, as well as for lead-free piezoelectric sensors and energy harvesting systems.

The development of a cost-effective process for the production of mesostructured aluminosilicates, with high Al content and controlled morphology, is highly desired. In this work, mesoporous aluminosilicates, with spherical morphology, have been synthesized under mild acidic aqueous conditions by using an aerosol-assisted sol–gel process, a simple, versatile and potentially scalable method. Two aluminum sources, aluminum isopropoxide and aluminum chloride, have been used, keeping constant the other synthesis and process parameters. FE-SEM, coupled with EDX, TEM and N2 adsorption–desorption measurements have shown that sprayed powders consist of microspheres, homogeneous in size and characterized by high surface areas (up to 640 m2 g−1) and narrow pore size distributions (centred at 2.5 nm). 27Al-NMR spectra of as-synthesized samples have evidenced mostly tetrahedral Al, also for the sample with higher Al content (Si/Al = 5.7). The surface acidity of the sprayed samples has been investigated by FT-IR spectroscopy of adsorbed ammonia and CO, which has shown the presence of Bronsted sites (able to protonate ammonia) and of weak Lewis sites.

We report the fabrication of a customized electronic platform for biosensing, integrating a single functionalized microwire between gold microelectrodes as a sensing element, including a custom microelectronic chip for signal readout. As a proof-of-concept, the platform was validated for the real-time detection of Bovine Serum Albumin (BSA) binding onto an NH2-functionalized zinc oxide (ZnO-NH2) microwire. The ZnO-NH2 microwires were deposited between two gold electrodes by means of a dielectrophoresis (DEP) technique. A Quasi-Digital Impedance Converter (QDIC) was conceived to constantly and instantaneously readout ZnO microwire impedance and transfer data to a laptop. Microelectrodes, a QDIC, a DEP generator, and data analysis were integrated in a stacked-card PCB configuration for a better noise reduction and usability. The system was able to distinguish between different BSA concentrations and to give real-time information about the binding process.

In this work flexible composite nanogenerators were prepared aiming to identify and optimize the exploitation of the piezoelectric effect in mechanical energy harvesting. A novel shape-controlled synthesis of ZnO microstructures through hydrothermal route was achieved resulting in different morphologies and aspect-ratio particles, microwires, multipods, and desert-roses. The three different microparticles and round-shaped commercial nanoparticles were incorporated into a polydimethylsiloxane matrix and a comparative study on the piezoelectric output power dependence on the filler morphology was carried out. The highest performances, i.e. output voltage of 10 V and a maximum power of 55 µW, were obtained with the highest aspect-ratio ZnO filler, the microwires, dispersed in the PDMS matrix at a 40 wt% concentration. Considering the generated voltage dependence on the size and aspect-ratio of the fillers, a working mechanism was formulated. The nanogenerators were then exploited to charge a homemade carbon-based supercapacitor. The voltage charging curves confirm the voltage generation trend based on the high aspect-ratio particles, showing that the best performances are obtained by the microwires-based composite nanogenerator. This work thus contributes to clarify the piezoelectric mechanism in composite nanogenerators and to maximize the output power generation in view of self-powered nanodevices able to recover and store waste environmental energy.

This paper presents a low-power system conceived for the integration and measurement of a nanowire (NW)-based sensor array onto a 130-nm CMOS technology process. Each array element includes a dielectrophoresis (DEP) signal generator for NWs alignment and a quasi-digital read-out circuit (ROC) for impedance conversion. The two subsystems can be digitally controlled by an external microcontroller which reads the ROC output and calculates the resistance and capacitance of the NW. Measurements show that the integrated two-quadrants quasi-digital ROC covers the range 1 $\text{M}\Omega $ –1 $\text{G}\Omega $ and 100 fF–1 $\mu \text{F}$ with a signal-to-noise ratio ≥44.89 dB. The CMOS system can be considered a building block for the implementation of a complete NW-based sensing array and each element, including both DEP and ROC subsystems, occupies an active area of 0.008 mm $^{2}$ and only consumes 14.76 $\mu \text{W}$ during read-out phase. The ROC has been also validated using an off-chip nanogap-based nanodevice integrating a single ZnO-NW which has been used as ultraviolet (UV) sensor during experiments. The device has been stimulated by an external UV source providing an irradiance $\geq93\mu \text{W}$ /cm $^{2}$ to the nanodevice surface. We have proved that the ROC is able to measure the ZnO-NW electrical characteristics and their variations due to the photogenerated charge carriers.

Zinc oxide (ZnO) thin films have been widely investigated due to their multifunctional properties, i.e., catalytic, semiconducting and optical. They have found practical use in a wide number of application fields. However, the presence of a compact micro/nanostructure has often limited the resulting material properties. Moreover, with the advent of low-dimensional ZnO nanostructures featuring unique physical and chemical properties, the interest in studying ZnO thin films diminished more and more. Therefore, the possibility to combine at the same time the advantages of thin-film based synthesis technologies together with a high surface area and a porous structure might represent a powerful solution to prepare ZnO thin films with unprecedented physical and chemical characteristics that may find use in novel application fields. Within this scope, this review offers an overview on the most successful synthesis methods that are able to produce ZnO thin films with both framework and textural porosities. Moreover, we discuss the related applications, mainly focused on photocatalytic degradation of dyes, gas sensor fabrication and photoanodes for dye-sensitized solar cells.

Among metal oxides, zinc oxide (ZnO) is one of the most attractive materials thanks to its biocompatible and biodegradable properties along with the existence of various morphologies featuring piezoelectric, semiconducting and photocatalytic activities. All of these structures were successfully prepared and tested for numerous applications, including optoelectronics, sensors and biomedical ones. In the last case, biocompatible ZnO nanomaterials positively influenced cells growth and tissue regeneration as well, promoting wound healing and new bone formation. Despite showing high surface areas, ZnO morphologies generally lack an intrinsic mesoporous structure, strongly limiting the investigation of the corresponding drug loading and release properties. Within this scope, this study focuses on the adsorption and release properties of high surface area, mesoporous ZnO structures using gentamicin sulfate (GS), a well known antibiotic against bacterial infections especially in orthopedics. The particular ZnO morphology was achieved starting from sputtered porous zinc layers, finally converted into ZnO by thermal oxidation. By taking advantage of this mesoporous framework, GS was successfully adsorbed within the ZnO matrix and the kinetic release profile evaluated for up to seven days. The adsorption of GS was successfully demonstrated, with a maximum amount of 263 mg effectively loaded per gram of active material. Then, fast kinetic release was obtained in vitro by simple diffusion mechanism, thus opening further possibilities of smart pore and surface engineering to improve the controlled delivery.

In recent years transdermal drug delivery has aroused significant interest as a sustained and non-invasive way of administering active substances. The advancements of nanotechnology allowed the development of novel pharmaceutical formulations overcoming skin barrier. Furthermore, such nano-system can be combined with conventional fabrics to pave the way to a new generation of wearable drug delivery devices: bio-functional garments. First the NP were produced by flash nanoprecipitation technique (FNP), the production process was optimized to produce particles with suitable size for transdermal applications. The nanoparticles were characterized in terms of drug content by UV-visible spectroscopy and in term of antioxidant activity by Electron Paramagnetic Resonance spectroscopy (EPR) coupled with spin trapping technique. The NPs were used to functionalize cotton and viscose-micromodal fabrics and the transdermal release properties were tested in vitro by Franz's Cell experiment. FNP was proven to be an effective technique to produce tunable size particles. Moreover, the nanoencapsulated drug exhibited antioxidant activity. The Franz's Cell test evidenced a controlled release behavior, providing evidence that the bio-functional textile is suitable for applications where sustained release and antioxidant properties are required.

This review focuses on the most recent applications of zinc oxide (ZnO) nanostructures for tissue engineering. ZnO is one of the most investigated metal oxides, thanks to its multifunctional properties coupled with the ease of preparing various morphologies, such as nanowires, nanorods, and nanoparticles. Most ZnO applications are based on its semiconducting, catalytic and piezoelectric properties. However, several works have highlighted that ZnO nanostructures may successfully promote the growth, proliferation and differentiation of several cell lines, in combination with the rise of promising antibacterial activities. In particular, osteogenesis and angiogenesis have been effectively demonstrated in numerous cases. Such peculiarities have been observed both for pure nanostructured ZnO scaffolds as well as for three-dimensional ZnO-based hybrid composite scaffolds, fabricated by additive manufacturing technologies. Therefore, all these findings suggest that ZnO nanostructures represent a powerful tool in promoting the acceleration of diverse biological processes, finally leading to the formation of new living tissue useful for organ repair.

Highly mesoporous ZnO and γ-Al2O3 nanowires (NWs) are both synthesized by a hydrothermal method using commercially available porous anodic aluminium oxide (AAO) as template. AAO membrane acts as template for ZnO NWs and both as template and precursor for γ-Al2O3 NWs. The formation of intermediate phases of porous Zn6Al2(OH)16CO3 and boehmite (γ-AlOOH) were observed, both occurring during the hydrothermal synthesis of porous ZnO and γ-Al2O3 NWs, respectively, and disappearing after annealing at 600 °C. This novel template-assisted hydrothermal process leads to the formation of porous ZnO and γ-Al2O3 NWs (specific surface area of 192 m2 g−1 and 263 m2 g−1, respectively), showing pore sizes around 4 nm in diameter. The influence of the reaction parameters on the nanostructure morphology was also investigated. A ZnO seed layer, deposited on the AAO channels prior to the hydrothermal synthesis, leads to more compact ZnO nanowires (99 m2 g−1) protecting the AAO host from the chemical attack of the precursor solution.