Bone Tissue Engineering and Nanotechnology: A Promising Combination for Bone Regeneration.

Large bone defects are the leading contributor to disability worldwide, affecting approximately 1.71 billion people. Conventional bone graft treatments show several disadvantages that negatively impact their therapeutic outcomes and limit their clinical practice. Therefore, much effort has been made to devise new and more effective approaches. In this context, bone tissue engineering (BTE), involving the use of biomaterials which are able to mimic the natural architecture of bone, has emerged as a key strategy for the regeneration of large defects. However, although different types of biomaterials for bone regeneration have been developed and investigated, to date, none of them has been able to completely fulfill the requirements of an ideal implantable material. In this context, in recent years, the field of nanotechnology and the application of nanomaterials to regenerative medicine have gained significant attention from researchers. Nanotechnology has revolutionized the BTE field due to the possibility of generating nanoengineered particles that are able to overcome the current limitations in regenerative strategies, including reduced cell proliferation and differentiation, the inadequate mechanical strength of biomaterials, and poor production of extrinsic factors which are necessary for efficient osteogenesis. In this review, we report on the latest in vitro and in vivo studies on the impact of nanotechnology in the field of BTE, focusing on the effects of nanoparticles on the properties of cells and the use of biomaterials for bone regeneration.

Microporous Fluorescent Poly(D,L-lactide) Acid-Carbon Nanodot Scaffolds for Bone Tissue Engineering Applications.

In this study, we introduce novel microporous poly(D,L-lactide) acid-carbon nanodot (PLA-CD) nanocomposite scaffolds tailored for potential applications in image-guided bone regeneration. Our primary objective was to investigate concentration-dependent structural variations and their relevance to cell growth, crucial aspects in bone regeneration. The methods employed included comprehensive characterization techniques such as DSC/TGA, FTIR, rheological, and degradation assessments, providing insights into the scaffolds' thermoplastic behavior, microstructure, and stability over time. Notably, the PLA-CD scaffolds exhibited distinct self-fluorescence, which persisted after 21 days of incubation, allowing detailed visualization in various multicolor modalities. Biocompatibility assessments were conducted by analyzing human adipose-derived stem cell (hADSC) growth on PLA-CD scaffolds, with results substantiated through cell viability and morphological analyses. hADSCs reached a cell viability of 125% and penetrated throughout the scaffold after 21 days of incubation. These findings underscore the scaffolds' potential in bone regeneration and fluorescence imaging. The multifunctional nature of the PLA-CD nanocomposite, integrating diagnostic capabilities with tunable properties, positions it as a promising candidate for advancing bone tissue engineering. Our study not only highlights key aspects of the investigation but also underscores the scaffolds' specific application in bone regeneration, providing a foundation for further research and optimization in this critical biomedical field.

Chlorpromazine's impact on Mytilus galloprovincialis: a multi-faceted investigation.

The antipsychotic chlorpromazine (Cpz) has raised concern as a pharmaceutical effluent due to its wide medical applications. Moreover, its potent pro-oxidant properties and impact on the cell viability of the marine mollusc Mytilus galloprovincialis, even at low concentrations (ng/L), have been noted. Based on this evidence, in this study, we investigated the physiological effects of Cpz on M. galloprovincialis, to elucidate its fate within the organism, in terms of bioaccumulation, biotransformation, byssus changes and stress responses of the cellular thiolome. Histological and indicators of vitality analyses were also performed to better evaluate the influence of the drug on the morphology and cell viability of the digestive gland. To this end, two different concentrations of Cpz (Cpz I (12 ng/L or 37 pM) and Cpz II (12 µg/L or 37 nM)) were administered to mussels over 14 days. Cpz accumulation in the digestive gland significantly increased with water concentration (BCF of Cpz I and Cpz II). Biochemical analyses indicated lysosomal dysfunction, reflected in elevated total Cathepsin D activity and compromised lysosomal membrane stability. Stress-related and metal-buffering proteins (GST and metallothionein) responded to both Cpz concentrations. Cpz I induced phase I biotransformation activity (CYP450-dependent EROD), while Cpz II triggered caspase-3 activation, indicative of detoxification overload. Histological analysis revealed digestive gland atrophy, epithelial thinning, haemocyte infiltration, and brown cell presence. Byssus analysis showed significant alterations. In conclusion, our study underscores Cpz-induced physiological and histological changes in M. galloprovincialis, posing potential implications for mussel health and confirming the utilisation of this mussel as an indication of Cpz ecotoxicity.

A Novel Serum-Based Diagnosis of Alzheimer's Disease Using an Advanced Phage-Based Biochip.

55 million people worldwide suffer from Alzheimer's disease (AD). A definitive diagnosis of AD is made postmortem after a neuropathological examination of the brain. There is an urgent need for an innovative, noninvasive methodology that allows for an early and reliable diagnosis. Several engineered phages that recognized Aß-autoantibodies present in the sera of AD patients are previously identified. Here, novel phages are tested for their ability to accurately discriminate AD sera using immunophage-polymerase chain reaction in a miniatured biochip. It is found that five of the six phages analyzed discriminate between healthy controls and AD patients. Further, by combining the response of two phages, non-AD and severe AD cases are identified with 100% accuracy and mild-to-moderate cases with 90% accuracy. While the number of cases used here are relatively small and can be confirmed in larger cohorts, this first-of-a-kind system represents an innovative methodology with the potential of having a major impact in the AD field: from a clinical perspective, it can aid physicians in making an accurate AD diagnosis; from a research perspective, it can be used as a surrogate for AD clinical trials.

Physiologic Response Evaluation of Human Foetal Osteoblast Cells within Engineered 3D-Printed Polylactic Acid Scaffolds.

Large bone defect treatments have always been one of the important challenges in clinical practice and created a huge demand for more efficacious regenerative approaches. The bone tissue engineering (BTE) approach offered a new alternative to conventional bone grafts, addressing all clinical needs. Over the past years, BTE research is focused on the study and realisation of new biomaterials, including 3D-printed supports to improve mechanical, structural and biological properties. Among these, polylactic acid (PLA) scaffolds have been considered the most promising biomaterials due to their good biocompatibility, non-toxic biodegradability and bioresorbability. In this work, we evaluated the physiological response of human foetal osteoblast cells (hFOB), in terms of cell proliferation and osteogenic differentiation, within oxygen plasma treated 3D-printed PLA scaffolds, obtained by fused deposition modelling (FDM). A mechanical simulation to predict their behaviour to traction, flexural or torque solicitations was performed. We found that: 1. hFOB cells adhere and grow on scaffold surfaces; 2. hFOB grown on oxygen plasma treated PLA scaffolds (PLA_PT) show an improvement of cell adhesion and proliferation, compared to not-plasma treated scaffolds (PLA_NT); 3. Over time, hFOB penetrate along strands, differentiate, and form a fibrous matrix, tissue-like; 4. 3D-printed PLA scaffolds have good mechanical behaviour in each analysed configuration. These findings suggest that 3D-printed PLA scaffolds could represent promising biomaterials for medical implantable devices in the orthopaedic field.

Biological Response Evaluation of Human Fetal Osteoblast Cells and Bacterial Cells on Fractal Silver Dendrites for Bone Tissue Engineering.

Prosthetic joint replacement is the most widely used surgical approach to repair large bone defects, although it is often associated with prosthetic joint infection (PJI), caused by biofilm formation. To solve the PJI problem, various approaches have been proposed, including the coating of implantable devices with nanomaterials that exhibit antibacterial activity. Among these, silver nanoparticles (AgNPs) are the most used for biomedical applications, even though their use has been limited by their cytotoxicity. Therefore, several studies have been performed to evaluate the most appropriate AgNPs concentration, size, and shape to avoid cytotoxic effects. Great attention has been focused on Ag nanodendrites, due to their interesting chemical, optical, and biological properties. In this study, we evaluated the biological response of human fetal osteoblastic cells (hFOB) and P. aeruginosa and S. aureus bacteria on fractal silver dendrite substrates produced by silicon-based technology (Si_Ag). In vitro results indicated that hFOB cells cultured for 72 h on the Si_Ag surface display a good cytocompatibility. Investigations using both Gram-positive (S. aureus) and Gram-negative (P. aeruginosa) bacterial strains incubated on Si_Ag for 24 h show a significant decrease in pathogen viability, more evident for P. aeruginosa than for S. aureus. These findings taken together suggest that fractal silver dendrite could represent an eligible nanomaterial for the coating of implantable medical devices.

The Role of the Transcription Factor Nrf2 in Alzheimer's Disease: Therapeutic Opportunities.

Alzheimer's disease (AD) is a common neurodegenerative disorder that affects the elderly. One of the key features of AD is the accumulation of reactive oxygen species (ROS), which leads to an overall increase in oxidative damage. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is a master regulator of the antioxidant response in cells. Under low ROS levels, Nrf2 is kept in the cytoplasm. However, an increase in ROS production leads to a translocation of Nrf2 into the nucleus, where it activates the transcription of several genes involved in the cells' antioxidant response. Additionally, Nrf2 activation increases autophagy function. However, in AD, the accumulation of Aß and tau reduces Nrf2 levels, decreasing the antioxidant response. The reduced Nrf2 levels contribute to the further accumulation of Aß and tau by impairing their autophagy-mediated turnover. In this review, we discuss the overwhelming evidence indicating that genetic or pharmacological activation of Nrf2 is as a potential approach to mitigate AD pathology.

Bioactive Composite Methacrylated Gellan Gum for 3D-Printed Bone Tissue-Engineered Scaffolds.

Gellan gum (GG) was chemically modified with methacrylic moieties to produce a photocrosslinkable biomaterial ink, hereinafter called methacrylated GG (GGMA), with improved physico-chemical properties, mechanical behavior and stability under physiological conditions. Afterwards, GGMA was functionalized by incorporating two different bioactive compounds, a naturally derived eumelanin extracted from the black soldier fly (BSF-Eumel), or hydroxyapatite nanoparticles (HAp), synthesized by the sol-gel method. Different ink formulations based on GGMA (2 and 4% (w/v)), BSF-Eumel, at a selected concentration (0.3125 mg/mL), or HAp (10 and 30% wHAp/wGGMA) were developed and processed by three-dimensional (3D) printing. All the functionalized GGMA-based ink formulations allowed obtaining 3D-printed GGMA-based scaffolds with a well-organized structure. For both bioactive signals, the scaffolds with the highest GGMA concentration (4% (w/v)) and the highest percentage of infill (45%) showed the best performances in terms of morphological and mechanical properties. Indeed, these scaffolds showed a good structural integrity over 28 days. Given the presence of negatively charged groups along the eumelanin backbone, scaffolds consisting of GGMA/BSF-Eumel demonstrated a higher stability. From a mechanical point of view, GGMA/BSF-Eumel scaffolds exhibited values of storage modulus similar to those of GGMA ones, while the inclusion of HAp at 30% (wHAp/wGGMA) led to a storage modulus of 32.5 kPa, 3.5-fold greater than neat GGMA. In vitro studies proved the capability of the bioactivated 3D-printed scaffolds to support 7F2 osteoblast cell growth and differentiation. BSF-Eumel and HAp triggered a different time-dependent physiological response in the osteoblasts. Specifically, while the ink with BSF-Eumel acted as a stimulus towards cell proliferation, reaching the highest value at 14 days, a higher expression of alkaline phosphatase activity was detected for scaffolds consisting of GGMA and HAp. The overall findings demonstrated the possible use of these biomaterial inks for 3D-printed bone tissue-engineered scaffolds.

Structural and antibacterial studies of novel ZnO and ZnxMn(1-x)O nanostructured titanium scaffolds for biomedical applications.

In the biomedical field, the demand for the development of broad-spectrum biomaterials able to inhibit bacterial growth is constantly increasing. Chronic infections represent the most serious and devastating complication related to the use of biomaterials. This is particularly relevant in the orthopaedic field, where infections can lead to implant loosening, arthrodesis, amputations and sometimes death. Antibiotics are the conventional approach for implanted-associated infections, but they have the limitation of increasing antibiotic resistance, a critical worldwide healthcare issue. In this context, the development of anti-infective biomaterials and infection-resistant surfaces can be considered the more effective strategy to prevent the implant colonisation and biofilm formation by bacteria, so reducing the occurrence of implant-associated infections. In the last years, inorganic nanostructures have become extremely appealing for chemical modifications or coatings of Ti surfaces, since they do not generate antibiotic resistance issues and are featured by superior stability, durability, and full compatibility with the sterilization process. In this work, we present a simple, rapid, and cheap chemical nanofunctionalization of titanium (Ti) scaffolds with colloidal ZnO and Mn-doped ZnO nanoparticles (NPs), prepared by a sol-gel method, exhibiting antibacterial activity. ZnO NPs and ZnxMn(1-x)O NPs formation with a size around 10-20nm and band gap values of 3.42 eV and 3.38 eV, respectively, have been displayed by characterization studies. UV-Vis, fluorescence, and Raman investigation suggested that Mn ions acting as dopants in the ZnO lattice. Ti scaffolds have been functionalized through dip coating, obtaining ZnO@Ti and ZnxMn(1-x)O@Ti biomaterials characterized by a continuous nanostructured film. ZnO@Ti and ZnxMn(1-x)O@Ti displayed an enhanced antibacterial activity against both Gram-positive Staphylococcus aureus (S. aureus) and Gram-negative Pseudomonas aeruginosa (P. aeruginosa) bacterial strains, compared to NPs in solution with better performance of ZnxMn(1-x)O@Ti respect to ZnO@Ti. Notably, it has been observed that ZnxMn(1-x)O@Ti scaffolds reach a complete eradication for S. aureus and 90 % of reduction for P. aeruginosa. This can be attributed to Zn2+ and Mn2+ metal ions release (as observed by ICP MS experiments) that is also maintained over time (72 h). To the best of our knowledge, this is the first study reported in the literature describing ZnO and Mn-doped ZnO NPs nanofunctionalized Ti scaffolds with improved antibacterial performance, paving the way for the realization of new hybrid implantable devices through a low-cost process, compatible with the biotechnological industrial chain method.

Galactosylated Polymer/Gold Nanorods Nanocomposites for Sustained and Pulsed Chemo-Photothermal Treatments of Hepatocarcinoma.

In this paper, we propose a rational design of a hybrid nanosystem capable of locally delivering a high amount of hydrophobic anticancer drugs (sorafenib or lenvatinib) and heat (hyperthermia) in a remote-controlled manner. We combined in a unique nanosystem the excellent NIR photothermal conversion of gold nanorods (AuNRs) with the ability of a specially designed galactosylated amphiphilic graft copolymer (PHEA-g-BIB-pButMA-g-PEG-GAL) able to recognize hepatic cells overexpressing the asialoglycoprotein receptor (ASGPR) on their membranes, thus giving rise to a smart composite nanosystem for the NIR-triggered chemo-phototherapy of hepatocarcinoma. In order to allow the internalization of AuNRs in the hydrophobic core of polymeric nanoparticles, AuNRs were coated with a thiolated fatty acid (12-mercaptododecanoic acid). The drug-loaded hybrid nanoparticles were prepared by the nanoprecipitation method, obtaining nanoparticles of about 200 nm and drug loadings of 9.0 and 5.4% w/w for sorafenib and lenvatinib, respectively. These multifunctional nanosystems have shown to convert NIR radiation into heat and release charged drugs in a remote-controlled manner. Then, the biocompatibility and synergistic effects of a chemo-phototherapy combination, as well the receptor-mediated internalization, were evaluated by an in vitro test on HepG2, HuH7, and NHDF. The results indicate that the proposed nanoparticles can be considered to be virtuous candidates for an efficient and selective dual-mode therapy of hepatocarcinoma.

A Curcumin-BODIPY Dyad and Its Silica Hybrid as NIR Bioimaging Probes.

In this paper we describe the synthesis of a novel bichromophoric system in which an efficient photoinduced intercomponent energy transfer process is active. The dyad consists of one subunit of curcumin and one of BODIPY and is able to emit in the far-red region, offering a large Stokes shift, capable of limiting light scattering processes for applications in microscopy. The system has been encapsulated in MCM-41 nanoparticles with dimensions between 50 and 80 nm. Both the molecular dyad and individual subunits were tested with different cell lines to study their effective applicability in bioimaging. MCM-41 nanoparticles showed no reduction in cell viability, indicating their biocompatibility and bio-inertness and making them capable of delivering organic molecules even in aqueous-based formulations, avoiding the toxicity of organic solvents. Encapsulation in the porous silica structure directed the location of the bichromophoric system within cytoplasm, while the dyad alone stains the nucleus of the hFOB cell line.

Recent Advances in Hydroxyapatite-Based Biocomposites for Bone Tissue Regeneration in Orthopedics.

Bone tissue is a nanocomposite consisting of an organic and inorganic matrix, in which the collagen component and the mineral phase are organized into complex and porous structures. Hydroxyapatite (HA) is the most used ceramic biomaterial since it mimics the mineral composition of the bone in vertebrates. However, this biomimetic material has poor mechanical properties, such as low tensile and compressive strength, which make it not suitable for bone tissue engineering (BTE). For this reason, HA is often used in combination with different polymers and crosslinkers in the form of composites to improve their mechanical properties and the overall performance of the implantable biomaterials developed for orthopedic applications. This review summarizes recent advances in HA-based biocomposites for bone regeneration, addressing the most widely employed inorganic matrices, the natural and synthetic polymers used as reinforcing components, and the crosslinkers added to improve the mechanical properties of the scaffolds. Besides presenting the main physical and chemical methods in tissue engineering applications, this survey shows that HA biocomposites are generally biocompatible, as per most in vitro and in vivo studies involving animal models and that the results of clinical studies on humans sometimes remain controversial. We believe this review will be helpful as introductory information for scientists studying HA materials in the biomedical field.

Metal-Based Nanoparticles: Antibacterial Mechanisms and Biomedical Application.

The growing increase in antibiotic-resistant bacteria has led to the search for new antibacterial agents capable of overcoming the resistance problem. In recent years, nanoparticles (NPs) have been increasingly used to target bacteria as an alternative to antibiotics. The most promising nanomaterials for biomedical applications are metal and metal oxide NPs, due to their intrinsic antibacterial activity. Although NPs show interesting antibacterial properties, the mechanisms underlying their action are still poorly understood, limiting their use in clinical applications. In this review, an overview of the mechanisms underlying the antibacterial activity of metal and metal oxide NPs will be provided, relating their efficacy to: (i) bacterial strain; (ii) higher microbial organizations (biofilm); (iii) and physico-chemical properties of NPs. In addition, bacterial resistance strategies will be also discussed to better evaluate the feasibility of the different treatments adopted in the clinical safety fields. Finally, a wide analysis on recent biomedical applications of metal and metal oxide NPs with antibacterial activity will be provided.

Applications of CRISPR-Cas9 in Alzheimer's Disease and Related Disorders.

Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease represent some of the most prevalent neurodegenerative disorders afflicting millions of people worldwide. Unfortunately, there is a lack of efficacious treatments to cure or stop the progression of these disorders. While the causes of such a lack of therapies can be attributed to various reasons, the disappointing results of recent clinical trials suggest the need for novel and innovative approaches. Since its discovery, there has been a growing excitement around the potential for CRISPR-Cas9 mediated gene editing to identify novel mechanistic insights into disease pathogenesis and to mediate accurate gene therapy. To this end, the literature is rich with experiments aimed at generating novel models of these disorders and offering proof-of-concept studies in preclinical animal models validating the great potential and versatility of this gene-editing system. In this review, we provide an overview of how the CRISPR-Cas9 systems have been used in these neurodegenerative disorders.

Multipotential Role of Growth Factor Mimetic Peptides for Osteochondral Tissue Engineering.

Articular cartilage is characterized by a poor self-healing capacity due to its aneural and avascular nature. Once injured, it undergoes a series of catabolic processes which lead to its progressive degeneration and the onset of a severe chronic disease called osteoarthritis (OA). In OA, important alterations of the morpho-functional organization occur in the cartilage extracellular matrix, involving all the nearby tissues, including the subchondral bone. Osteochondral engineering, based on a perfect combination of cells, biomaterials and biomolecules, is becoming increasingly successful for the regeneration of injured cartilage and underlying subchondral bone tissue. To this end, recently, several peptides have been explored as active molecules and enrichment motifs for the functionalization of biomaterials due to their ability to be easily chemically synthesized, as well as their tunable physico-chemical features, low immunogenicity issues and functional group modeling properties. In addition, they have shown a good aptitude to penetrate into the tissue due to their small size and stability at room temperature. In particular, growth-factor-derived peptides can play multiple functions in bone and cartilage repair, exhibiting chondrogenic/osteogenic differentiation properties. Among the most studied peptides, great attention has been paid to transforming growth factor-ß and bone morphogenetic protein mimetic peptides, cell-penetrating peptides, cell-binding peptides, self-assembling peptides and extracellular matrix-derived peptides. Moreover, recently, phage display technology is emerging as a powerful selection technique for obtaining functional peptides on a large scale and at a low cost. In particular, these peptides have demonstrated advantages such as high biocompatibility; the ability to be immobilized directly on chondro- and osteoinductive nanomaterials; and improving the cell attachment, differentiation, development and regeneration of osteochondral tissue. In this context, the aim of the present review was to go through the recent literature underlining the importance of studying novel functional motifs related to growth factor mimetic peptides that could be a useful tool in osteochondral repair strategies. Moreover, the review summarizes the current knowledge of the use of phage display peptides in osteochondral tissue regeneration.

Physicochemical Characterization and Antibacterial Properties of Carbon Dots from Two Mediterranean Olive Solid Waste Cultivars.

Carbon nanomaterials have shown great potential in several fields, including biosensing, bioimaging, drug delivery, energy, catalysis, diagnostics, and nanomedicine. Recently, a new class of carbon nanomaterials, carbon dots (CDs), have attracted much attention due to their easy and inexpensive synthesis from a wide range of precursors and fascinating physical, chemical, and biological properties. In this work we have developed CDs derived from olive solid wastes of two Mediterranean regions, Puglia (CDs_P) and Calabria (CDs_C) and evaluated them in terms of their physicochemical properties and antibacterial activity against Staphylococcus aureus (S. aureus) and Pseudomonas aeruginosa (P. aeruginosa). Results show the nanosystems have a quasi-spherical shape of 12-18 nm in size for CDs_P and 15-20 nm in size for CDs_C. UV-Vis characterization indicates a broad absorption band with two main peaks at about 270 nm and 300 nm, respectively, attributed to the π-π* and n-π* transitions of the CDs, respectively. Both samples show photoluminescence (PL) spectra excitation-dependent with a maximum at λem = 420 nm (λexc = 300 nm) for CDs_P and a red-shifted at λem = 445 nm (λexc = 300 nm) for CDs_C. Band gaps values of ≈ 1.48 eV for CDs_P and ≈ 1.53 eV for CDs_C are in agreement with semiconductor behaviour. ζ potential measures show very negative values for CDs_C compared to CDs_P (three times higher, -38 mV vs. -18 mV at pH = 7). The evaluation of the antibacterial properties highlights that both CDs have higher antibacterial activity towards Gram-positive than to Gram-negative bacteria. In addition, CDs_C exhibit bactericidal behaviour at concentrations of 360, 240, and 120 µg/mL, while lesser activity was found for CDs_P (bacterial cell reduction of only 30% at the highest concentration of 360 µg/mL). This finding was correlated to the higher surface charge of CDs_C compared to CDs_P. Further investigations are in progress to confirm this hypothesis and to gain insight on the antibacterial mechanism of both cultivars.

The Biological Function of MicroRNAs in Bone Tumors.

Micro ribonucleic acids (miRNAs) are small endogenous noncoding RNAs molecules that regulate gene expression post-transcriptionally. A single miRNA is able to target hundreds of specific messenger RNA (mRNAs) by binding to the 3'-untranslated regions. miRNAs regulate different biological processes such as cell proliferation, differentiation and apoptosis. Altered miRNA expression is certainly related to the development of the most common human diseases, including tumors. Osteosarcoma (OS), Ewing's Sarcoma (ES), and Chondrosarcoma (CS) are the most common primary bone tumors which affect mainly children and adolescents. A significant dysregulation of miRNA expression, in particular of mir-34, mir-21, mir-106, mir-143, and miR-100, has been revealed in OS, ES and CS. In this context, miRNAs can act as either tumor suppressor genes or oncogenes, contributing to the initiation and progression of bone tumors. The in-depth study of these small molecules can thus help to better understand their biological functions in bone tumors. Therefore, this review aims to examine the potential role of miRNAs in bone tumors, especially OS, ES and CS, and to suggest their possible use as potential therapeutic targets for the treatment of bone tumors and as biomarkers for early diagnosis.

SARS-CoV-2 and omicron variant detection with a high selectivity, sensitivity, and low-cost silicon bio-nanosensor.

The recent SARS-CoV-2 pandemic has highlighted the urgent need for novel point-of-care devices to be promptly used for a rapid and reliable large screening analysis of several biomarkers like genetic sequences and antibodies. Currently, one of the main limitations of rapid tests is the high percentage of false negatives in the presence of variants and, in particular for the Omicron one. We demonstrate in this work the detection of SARS-CoV-2 and the Omicron variant with a cost-effective silicon nanosensor enabling high sensitivity, selectivity, and fast response. We have shown that a silicon (Si) nanowires (NW) platform detects both Sars-CoV-2 and its Omicron variant with a limit of detection (LoD) of four effective copies (cps), without any amplification of the genome, and with high selectivity. This ultrasensitive detection of 4 cps allows to obtain an extremely early diagnosis paving the way for efficient and widespread tracking. The sensor is made with industrially compatible techniques, which in perspective may allow easy and cost-effective industrialization.

Nucleic Acids Analytical Methods for Viral Infection Diagnosis: State-of-the-Art and Future Perspectives.

The analysis of viral nucleic acids (NA), DNA or RNA, is a crucial issue in the diagnosis of infections and the treatment and prevention of related human diseases. Conventional nucleic acid tests (NATs) require multistep approaches starting from the purification of the pathogen genetic material in biological samples to the end of its detection, basically performed by the consolidated polymerase chain reaction (PCR), by the use of specialized instruments and dedicated laboratories. However, since the current NATs are too constraining and time and cost consuming, the research is evolving towards more integrated, decentralized, user-friendly, and low-cost methods. These will allow the implementation of massive diagnoses addressing the growing demand of fast and accurate viral analysis facing such global alerts as the pandemic of coronavirus disease of the recent period. Silicon-based technology and microfluidics, in this sense, brought an important step up, leading to the introduction of the genetic point-of-care (PoC) systems. This review goes through the evolution of the analytical methods for the viral NA diagnosis of infection diseases, highlighting both advantages and drawbacks of the innovative emerging technologies versus the conventional approaches.

Carbon Dots: An Innovative Tool for Drug Delivery in Brain Tumors.

Brain tumors are particularly aggressive and represent a significant cause of morbidity and mortality in adults and children, affecting the global population and being responsible for 2.6% of all cancer deaths (as well as 30% of those in children and 20% in young adults). The blood-brain barrier (BBB) excludes almost 100% of the drugs targeting brain neoplasms, representing one of the most significant challenges to current brain cancer therapy. In the last decades, carbon dots have increasingly played the role of drug delivery systems with theranostic applications against cancer, thanks to their bright photoluminescence, solubility in bodily fluids, chemical stability, and biocompatibility. After a summary outlining brain tumors and the current drug delivery strategies devised in their therapeutic management, this review explores the most recent literature about the advances and open challenges in the employment of carbon dots as both diagnostic and therapeutic agents in the treatment of brain cancers, together with the strategies devised to allow them to cross the BBB effectively.