Carbon Nanomaterials: Efficacy and Safety for Nanomedicine

Carbon nanomaterials, including fullerenes, carbon nanohorns, and carbon nanotubes, are increasingly being used in various fields owing to these materials’ unique, size-dependent functions and physicochemical properties. Recently, because of their high variability and stability, carbon nanomaterials have been explored as a novel tool for the delivery of therapeutic molecules including peptide and nucleic acid cancer drugs. However, insufficient information is available regarding the safety of carbon nanomaterials for human health, even though such information is vital for the development of safe and effective nanomedicine technologies. In this review, we discuss currently available information regarding the safety of carbon nanomaterials in nanomedicine applications, including information obtained from our own studies; and we discuss types of carbon nanomaterials that demonstrate particular promise for safe nanomedicine technologies.     

Active Nanomaterials to Meet the Challenge of Dental Pulp Regeneration

The vitality of the pulp is fundamental to the functional life of the tooth. For this aim, active and living biomaterials are required to avoid the current drastic treatment, which is the removal of all the cellular and molecular content regardless of its regenerative potential. The regeneration of the pulp tissue is the dream of many generations of dental surgeons and will revolutionize clinical practices. Recently, the potential of the regenerative medicine field suggests that it would be possible to achieve such complex regeneration. Indeed, three crucial steps are needed: the control of infection and inflammation and the regeneration of lost pulp tissues. For regenerative medicine, in particular for dental pulp regeneration, the use of nano-structured biomaterials becomes decisive. Nano-designed materials allow the concentration of many different functions in a small volume, the increase in the quality of targeting, as well as the control of cost and delivery of active molecules. Nanomaterials based on extracellular mimetic nanostructure and functionalized with multi-active therapeutics appear essential to reverse infection and inflammation and concomitantly to orchestrate pulp cell colonization and differentiation. This novel generation of nanomaterials seems very promising to meet the challenge of the complex dental pulp regeneration.     

New Electrochemical Sensor Based on Hierarchical Carbon Nanofibers with NiCo Nanoparticles and Its Application for Cetirizine Hydrochloride Determination

A new electrochemical sensor based on hierarchical carbon nanofibers with Ni and Co nanoparticles (eCNF/CNT/NiCo-GCE) was developed. The presented sensor may be characterized by high sensitivity, good electrical conductivity, and electrocatalytic properties. Reproducibility of its preparation expressed as %RSD (relative standard deviation) was equal to 9.7% (n = 5). The repeatability of the signal register on eCNF/CNT/NiCo-GCE was equal to 3.4% (n = 9). The developed sensor was applied in the determination of the antihistamine drug—cetirizine hydrochloride (CTZ). Measurement conditions, such as DPV (differential pulse voltammetry) parameters, supporting electrolyte composition and concentration were optimized. CTZ exhibits a linear response in three concentration ranges: 0.05–6 µM (r = 0.988); 7–32 (r = 0.992); and 42–112 (r = 0.999). Based on the calibration performed, the limit of detection (LOD) and limit of quantification (LOQ) were calculated and were equal to 14 nM and 42 nM, respectively. The applicability of the optimized method for the determination of CTZ was proven by analysis of its concentration in real samples, such as pharmaceutical products and body fluids (urine and plasma). The results were satisfactory and the calculated recoveries (97–115%) suggest that the method may be considered accurate. The obtained results proved that the developed sensor and optimized method may be used in routine laboratory practice.     

Ceramic Nanofiber Materials for Wound Healing and Bone Regeneration: A Brief Review

Ceramic nanofibers have been shown to be a new horizon of research in the biomedical area, due to their differentiated morphology, nanoroughness, nanotopography, wettability, bioactivity, and chemical functionalization properties. Therefore, considering the impact caused by the use of these nanofibers, and the fact that there are still limited data available in the literature addressing the ceramic nanofiber application in regenerative medicine, this review article aims to gather the state-of-the-art research concerning these materials, for potential use as a biomaterial for wound healing and bone regeneration, and to analyze their characteristics when considering their application.     

Light-Driven Flying Balloons Based on Hybrids of Carbon Nanotubes and Cellulose Nanofibers

We have fabricated nanocarbon-based palm-sized cubic paper balloons that can be levitated by light irradiation. These paper balloons are composed of carbon nanotube (CNT) freestanding films and cellulose nanofiber (CNF) freestanding films. The number of CNT freestanding films (N_CNT) and the number of CNF freestanding films (6-N_CNT) among the six walls of the cube were varied. We investigated the effect of N_CNT on the levitation behaviors under light irradiation. We found that the balloons were levitated when N_CNT was greater than or equal to two. The levitation height was found to be increased by increasing N_CNT.     

Bioassay chamber for angiogenesis with perfused explanted arteries and electrospun scaffolding

OBJECTIVE: The purpose of this study was to test the hypothesis that explanted perfused arteries can serve as the initial endothelial cell culture source to evaluate the onset of angiogenesis in a cellulose acetate electrospun scaffold. METHODS: Electrospun scaffolds with fiber diameters roughly controlled in three broad ranges: 0.01 to 0.2, 0.2 to 1, and 1 to 5 microm (Nanomed Nanotechnol Biol Med 2:37-41, 2006), were used in cell culture to determine which provides the best culture topology. This scaffold was then tested in a bioassay chamber whose cellular source was an explanted abdominal aorta from donated euthanized mice. Scaffolds were draped over a cannulated vessel perfused for 24 h. Cell viability, density, and morphology were quantified. RESULTS: The largest fiber diameter group provided the best culture topology for human umbilical vein endothelial cells, showing high cell viability and density, and enhanced elongated cell morphology. Addition of single-walled carbon nanotubes decreased cell density significantly but chitosan heightened cell density and promoted spontaneous capillary tube like structure. Viability of endothelial cells increased with higher flow in the bioassay chamber. CONCLUSIONS: Endothelial cells showed a growth preference towards larger diameter fibers. Addition of chitosan improved culture conditions. Thus, this study provides a proof of principle for the possibility of co-culturing tissue engineered vascular networks from a perfused explant.     

Synthetic Injectable Biomaterials for Alveolar Bone Regeneration in Animal and Human Studies

After tooth extraction, the alveolar ridge undergoes dimensional changes. Different bone regeneration biomaterials are used to reduce bone loss. The aim of this article was to systematically review the literature on the effect of injectable synthetic biomaterials and their advantages and disadvantages for new bone formation in the maxilla and mandible in animals and humans. A literature search was conducted in November 2020 via MEDLINE PubMed, Cochrane, and Embase. Of the 501 records screened, abstract analysis was performed on 49 articles, resulting in 21 studies that met the inclusion criteria. Animal studies have shown heterogeneity in terms of animal models, follow-up time, composition of the injectable biomaterial, and different outcome variables such as bone–implant contact, newly formed bone, and peri-implant bone density. Heterogeneity has also been demonstrated by human studies. The following outcomes were observed: newly formed bone, connective tissue, residual injectable bone graft substitute, radiographic density, residual bone height, and different follow-up periods. Further studies, especially in humans, based on the histological and biomechanical properties of the injectable delivery form, are needed to draw more concrete conclusions that will contribute to a better understanding of the benefits of this type of biomaterials and their role in bone regeneration.     

Enhancing Crystallinity and Orientation by Hot-Stretching to Improve the Mechanical Properties of Electrospun Partially Aligned Polyacrylonitrile (PAN) Nanocomposites

Partially aligned polyacrylonitrile (PAN)-based nanofibers were electrospun from PAN and PAN/single-walled carbon nanotubes (SWNTs) in a solution of dimethylformamide (DMF) to make the nanofiber composites. The as-spun nanofibers were then hot-stretched in the oven to enhance its orientation and crystallinity. With the introduction of SWNTs and by the hot-stretched process, the mechanical properties will be enhanced correspondingly. Scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray scattering (XRD), differential scanning calorimetry (DSC), and the tensile test were used to characterize the microstructure and performances of the nanofibers. The orientation and crystallinity of the as-spun and hot-stretched nanofibers confirmed by X-ray have increased. Differential scanning calorimetry showed that the glass transition temperature of PAN increased about 3 °C by an addition of 0.75 wt% SWNTs indicating a strong interfacial interaction between PAN and SWNTs. The tensile strength and the modulus of the nanofibers increased revealing significant load transfer across the nanotube-matrix interface. For PAN nanofibers, the improved fiber alignment, orientation and crystallinity resulted in enhanced mechanical properties, such as the tensile strength and modulus of the nanofibers. It was concluded that the hot-stretched nanofiber and the PAN/SWNTs nanofibers can be used as a potential precursor to produce high-performance nanocomposites.     

Alloplastic Bone Substitutes for Periodontal and Bone Regeneration in Dentistry: Current Status and Prospects

Various bone graft products are commercially available worldwide. However, there is no clear consensus regarding the appropriate bone graft products in different clinical situations. This review is intended to summarize bone graft products, especially alloplastic bone substitutes that are available in multiple countries. It also provides dental clinicians with detailed and accurate information concerning these products. Furthermore, it discusses the prospects of alloplastic bone substitutes based on an analysis of the current market status, as well as a comparison of trends among countries. In this review, we focus on alloplastic bone substitutes approved in the United States, Japan, and Korea for use in periodontal and bone regeneration. According to the Food and Drug Administration database, 87 alloplastic bone graft products have been approved in the United States since 1996. According to the Pharmaceuticals and Medical Devices Agency database, 10 alloplastic bone graft products have been approved in Japan since 2004. According to the Ministry of Health and Welfare database, 36 alloplastic bone graft products have been approved in Korea since 1980. The approved products are mainly hydroxyapatite, β-tricalcium phosphate, and biphasic calcium phosphate. The formulations of the products differed among countries. The development of new alloplastic bone products has been remarkable. In the near future, alloplastic bone substitutes with safety and standardized quality may be the first choice instead of autologous bone; they may offer new osteoconductive and osteoinductive products with easier handling form and an adequate resorption rate, which can be used with growth factors and/or cell transplantation. Careful selection of alloplastic bone graft products is necessary to achieve predictable outcomes according to each clinical situation.     

Carbon Nanomaterials for Enhancing the Thermal,Physical and Rheological Properties of Asphalt Binders

Effective thermal conduction modification in asphalt binders is beneficial to reducing pavement surface temperature and relieving the urban heat island (UHI) effect in the utilization of solar harvesting and snow melting pavements. This study investigated the performance of two nanometer-sized modifiers, graphene (Gr) and carbon nanotubes (CNTs), on enhancing the thermal, physical and rheological properties of asphalt binders. Measurements depending on a transient plant source method proved that both Gr and CNTs linearly increased the thermal conductivity and thermal diffusivity of asphalt binders, and while 5% Gr by volume of matrix asphalt contributed to 300% increments, 5% CNTs increased the two parameters of asphalt binders by nearly 72% at 20 °C. Meanwhile, a series of empirical and rheological properties experiments were conducted. The results demonstrated the temperature susceptibility reduction and high-temperature properties promotion of asphalt binders by adding Gr or CNTs. The variation trends in the anti-cracking properties of asphalt binders modified by Gr and CNTs with the modifier content differed at low temperatures, which may be due to the unique nature of Gr. In conclusion, Gr, whose optimal content is 3% by volume of matrix asphalt, provides superior application potential for solar harvesting and snow melting pavements in comparison to CNTs due to its comprehensive contributions to thermal properties, construction feasibility, high-temperature performance and low-temperature performance of asphalt binders.     

Multiple Porous Synthetic Bone Graft Comprising EngineeredMicro-Channel for Drug Carrier and Bone Regeneration

Due to high demand but limited supply, there has been an increase in the need to replace autologous bone grafts with alternatives that fulfill osteogenic requirements. In this study, two different types of bone grafts were tested for their drug carrying abilities along with their osteogenic properties. Two different types of alendronate-loaded bone grafts, Bio-Oss (bovine bone graft) and InRoad (biphasic synthetic bone graft) were observed to see how different concentrations of alendronate would affect the sustained release to enhance osteogenesis. In this study, defected ovariectomize-induced osteoporotic rat calvarias were observed for 28 days with three different concentrations of alendronate (0 mg, 1 mg, 5 mg) for both Bio-Oss and InRoad. A higher concentration (5 mg) allowed for a more controlled and sustained release throughout the 28-day comparison to those of lower concentrations (0 mg, 1 mg). When comparing Bio-Oss and InRoad through histology and Micro-CT, InRoad showed higher enhancement in osteogenesis. Through this study, it was observed that alendronate not only brings out robust osteogenesis with InRoad bone grafts, but also enhances bone regeneration in an alendronate-concentration-dependent manner. The combination of higher concentration of alendronate and multiple porous bone graft containing internal micro-channel structure of InRoad resulted in higher osteogenesis with a sustained release of alendronate.     

Insights into Nanomedicine for Head and Neck Cancer Diagnosis and Treatment

Head and neck cancers rank sixth among the most common cancers today, and the survival rate has remained virtually unchanged over the past 25 years, due to late diagnosis and ineffective treatments. They have two main risk factors, tobacco and alcohol, and human papillomavirus infection is a secondary risk factor. These cancers affect areas of the body that are fundamental for the five senses. Therefore, it is necessary to treat them effectively and non-invasively as early as possible, in order to do not compromise vital functions, which is not always possible with conventional treatments (chemotherapy or radiotherapy). In this sense, nanomedicine plays a key role in the treatment and diagnosis of head and neck cancers. Nanomedicine involves using nanocarriers to deliver drugs to sites of action and reducing the necessary doses and possible side effects. The main purpose of this review is to give an overview of the applications of nanocarrier systems to the diagnosis and treatment of head and neck cancer. Herein, several types of delivery strategies, radiation enhancement, inside-out hyperthermia, and theragnostic approaches are addressed.     

Electrospun Nanofibers and Electrochemical Techniques for the Detection of Heavy Metal Ions

Contamination by heavy metals is currently one of the most environmental concerns especially due to the toxicity, pervasiveness, and persistence of these substances. As they are not biodegradable, heavy metals are harmful not only for water, air, and soil but also for human health, even in very low traces. There is therefore a pressing need to develop an efficient, economic, and rapid analysis method to be applied in a wide range of conditions and able to detect very low contaminants concentrations. Currently, the most novel solution in this field is represented by the combination of electrospun nanofibers and highly sensitive electrochemical techniques. It has been proved that nanofibers, due to their outstanding properties, perfectly fit as sensing material when trace concentrations of heavy metals were investigated by anodic stripping voltammetry, envisaged as the most sensitive electrochemical technique for this kind of measurements. This work aims to provide an overview of the latest trends in the detection of contaminants by the simultaneous use of electrospun fibers and anodic stripping voltammetry. Indeed, a clear and comprehensive vision of the current status of this research may drive future improvements and new challenges.     

Evolution of Microstructure,Texture and Mechanical Properties for Multilayered Al Matrix Composites by Accumulative Roll Bonding

Carbon nanotubes (CNTs) reinforced aluminum matrix nanocomposites were fabricated by Accumulative Roll Bonding (ARB). The surface morphologies, mechanical properties, grains texture and orientation of the Al/CNTs nanocomposites were characterized, and the mechanisms and influences of CNTs contents and ARB cycles on the mechanical performance and grain textures of Al/CNTs were investigated and revealed. The strength of the composites rose with increase of the CNTs content, and the ARB cycles showed a 26% improvement when the CNTs content varied from 0 to 1 volume percent (vol.%). The increase in the mass fraction of the carbon nanotubes made the grain distribution in the Al/CNTs nanocomposite samples more diffuse. Besides, the stable texture of the hot rolled crystal grains on the α orientation are constantly turning to {011}< 011> with the mass fraction of the reinforcing phase increased.     

Efficacy of Long‐Term Treatment With Tolvaptan to Prolong the Time Until Dialysis Initiation in Patients With Chronic Kidney Disease and Heart Failure

The short‐term effectiveness of tolvaptan (TLV) against heart failure has been established. TLV is known to decrease the worsening of renal function more than loop diuretics. Long‐term TLV administration decreases the rate of re‐hospitalization in heart failure and prevents deterioration of kidney function. If repeated hospitalization for heart failure can be prevented in patients having concurrent chronic kidney disease (CKD), the period until dialysis initiation may be prolonged. We investigated whether long‐term TLV management can extend the period until dialysis initiation in patients with CKD and heart failure. A retrospective, observational study was conducted among patients with CKD stage G4 and G5 admitted because of heart failure between April 2013 and July 2018. They were divided into those with TLV and those without TLV. They were followed up until August 2018 and relevant data was collected. Data from 115 patients (68 men and 47 women), with a mean age of 73.4 ± 11.9 (median 76.0 and IQR 66.5–82.0) years and a mean eGFR of 11.8 ± 5.7 (median 9.9 and IQR 7.5–14.8) mL/min/1.73m² were included in the analysis. Twenty‐five patients had received long‐term TLV treatment, and 90 had not. Multivariate analysis after adjustment showed that long‐term use of TLV significantly lowered the hazard ratio (HR) for time taken to reach dialysis initiation (HR: 0.3286, 95%CI: 0.1282–0.8423, P = 0.0205). Propensity score‐matched analysis showed similar results (HR: 0.3220, 95%CI: 0.1107–0.9369, P = 0.0376). In patients with CKD G4 and G5 and heart failure, long‐term treatment with TLV can prolong the time until dialysis initiation.     

The Role of Labile Iron in Kidney Disease and Treatment with Chelation

There are two major forms of kidney disease: acute renal failure [also referred to as acute kidney injury (AKI)] and chronic kidney disease (CKD). Acute renal failure is an abrupt loss of kidney function within 48 h, whereas CKD is a loss of kidney function greater than 3 months. There is a large amount of experimental evidence for an increase of labile iron in a wide variety of models of kidney disease. Additionally, iron chelators provide protection, indicating an important role of labile iron in these diseases. These observations suggest that iron chelators may provide a new modality of prevention and treatment of kidney disease.     

Hybrid Membranes of PLLA/Collagen for Bone Tissue Engineering: A Comparative Study of Scaffold Production Techniques for Optimal Mechanical Properties and Osteoinduction Ability

Synthetic and natural polymer association is a promising tool in tissue engineering. The aim of this study was to compare five methodologies for producing hybrid scaffolds for cell culture using poly-l-lactide (PLLA) and collagen: functionalization of PLLA electrospun by (1) dialkylamine and collagen immobilization with glutaraldehyde and by (2) hydrolysis and collagen immobilization with carbodiimide chemistry; (3) co-electrospinning of PLLA/chloroform and collagen/hexafluoropropanol (HFP) solutions; (4) co-electrospinning of PLLA/chloroform and collagen/acetic acid solutions and (5) electrospinning of a co-solution of PLLA and collagen using HFP. These materials were evaluated based on their morphology, mechanical properties, ability to induce cell proliferation and alkaline phosphatase activity upon submission of mesenchymal stem cells to basal or osteoblastic differentiation medium (ODM). Methods (1) and (2) resulted in a decrease in mechanical properties, whereas methods (3), (4) and (5) resulted in materials of higher tensile strength and osteogenic differentiation. Materials yielded by methods (2), (3) and (5) promoted osteoinduction even in the absence of ODM. The results indicate that the scaffold based on the PLLA/collagen blend exhibited optimal mechanical properties and the highest capacity for osteodifferentiation and was the best choice for collagen incorporation into PLLA in bone repair applications.     

Surface Engineering of Nanomaterials with Polymers,Biomolecules, and Small Ligands for Nanomedicine

Nanomedicine is a speedily growing area of medical research that is focused on developing nanomaterials for the prevention, diagnosis, and treatment of diseases. Nanomaterials with unique physicochemical properties have recently attracted a lot of attention since they offer a lot of potential in biomedical research. Novel generations of engineered nanostructures, also known as designed and functionalized nanomaterials, have opened up new possibilities in the applications of biomedical approaches such as biological imaging, biomolecular sensing, medical devices, drug delivery, and therapy. Polymers, natural biomolecules, or synthetic ligands can interact physically or chemically with nanomaterials to functionalize them for targeted uses. This paper reviews current research in nanotechnology, with a focus on nanomaterial functionalization for medical applications. Firstly, a brief overview of the different types of nanomaterials and the strategies for their surface functionalization is offered. Secondly, different types of functionalized nanomaterials are reviewed. Then, their potential cytotoxicity and cost-effectiveness are discussed. Finally, their use in diverse fields is examined in detail, including cancer treatment, tissue engineering, drug/gene delivery, and medical implants.     

Renin-Angiotensin System Blockers and the Risk of COVID-19–Related Mortality in Patients with Kidney Failure

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