Search Results (15)

Onychomycosis, a fungal nail infection, affects about 4% of the global population. Current topical antifungals like ciclopirox and amorolfine have limited effectiveness, highlighting the need for better treatments. WSNS-PO is a novel water-soluble therapy designed to treat and prevent onychomycosis by enhancing nail health. This study evaluated WSNS-PO’s ability to penetrate the nail plate and to treat and prevent infection by Trichophyton rubrum using bovine hoof membranes and human nail clippings. The anti-fungal efficacy of WSNS-PO was additionally evaluated against other dermatophytes, non-dermatophyte fungi, and yeast. The results showed that WSNS-PO effectively permeated nails and reduced and prevented the colonization of human nail fragments by T. rubrum ex vivo, demonstrating an efficacy comparable to ciclopirox and amorolfine. WSNS-PO also prevented the transfer of T. rubrum infection between nails and inhibited the fungal colonization of human skin by dermatophyte and non-dermatophyte fungi and yeast. Together, these results indicate that WSNS-PO possesses fungistatic, barrier-forming, and anti-adhesive properties, suggesting that it holds promise as an onychomycosis treatment against dermatophytes, yeast, and molds. Full article

Visual examination of nails can reflect human health status. Diseases such as nutritive imbalances and skin diseases can be identified by looking at the colors around the plate part of the nails. We present the AI-based NAILS method to detect fingernails through segmentation and labeling. The NAILS leverages a pre-trained Convolutional Neural Network model to segment and label fingernail regions from fingernail images, normalizing RGB values to monitor tiny color changes via a GUI and the use of an HD webcam in real time. The use of normalized RGB values combined with AI-based segmentation for real-time health monitoring is novel and innovative. The NAILS algorithm could be used to self-extract and archive primary signs of diseases in humans, especially in rural areas or when other testing may be not available. Full article

This article reviews the research and development focus of metallic glasses in the field of biomedical applications. Metallic glasses exhibit a short-range ordered and long-range disordered glassy structure at the microscopic level, devoid of structural defects such as dislocations and grain boundaries. Therefore, they possess advantages such as high strength, toughness, and corrosion resistance, combining characteristics of both metals and glasses. This novel alloy system has found applications in the field of biomedical materials due to its excellent comprehensive performance. This review discusses the applications of Ti-based bulk metallic glasses in load-bearing implants such as bone plates and screws for long-term implantation. On the other hand, Mg-based metallic glasses, owing to their degradability, are primarily used in degradable bone nails, plates, and vascular stents. However, metallic glasses as biomaterials still face certain challenges. The Young’s modulus value of Ti-based metallic glasses is higher than that of human bones, leading to stress-shielding effects. Meanwhile, Mg-based metallic glasses degrade too quickly, resulting in the premature loss of mechanical properties and the formation of numerous bubbles, which hinder tissue healing. To address these issues, we propose the following development directions: (1) Introducing porous structures into titanium-based metallic glasses is an important research direction for reducing Young’s modulus; (2) To enhance the bioactivity of implant material surfaces, the surface modification of titanium-based metallic glasses is essential. (3) Developing antibacterial coatings and incorporating antibacterial metal elements into the alloys is essential to maintain the long-term effective antibacterial properties of metallic biomaterials. (4) Corrosion resistance must be further improved through the preparation of composite materials, while ensuring biocompatibility and safety, to achieve controllable degradation rates and degradation modes. Full article

Onychomycosis, or fungal nail infection, causes not only pain and discomfort but can also have psychological and social consequences for the patient. Treatment of onychomycosis is complicated by the location of the infection under the nail plate, meaning that antifungal molecules must either penetrate the nail or be applied systemically. Currently, available treatments are limited by their poor nail penetration for topical products or their potential toxicity for systemic products. Plant defensins with potent antifungal activity have the potential to be safe and effective treatments for fungal infections in humans. The cystine-stabilized structure of plant defensins makes them stable to the extremes of pH and temperature as well as digestion by proteases. Here, we describe a novel plant defensin, Ppdef1, as a peptide for the treatment of fungal nail infections. Ppdef1 has potent, fungicidal activity against a range of human fungal pathogens, including Candida spp., Cryptococcus spp., dermatophytes, and non-dermatophytic moulds. In particular, Ppdef1 has excellent activity against dermatophytes that infect skin and nails, including the major etiological agent of onychomycosis Trichophyton rubrum. Ppdef1 also penetrates human nails rapidly and efficiently, making it an excellent candidate for a novel topical treatment of onychomycosis. Full article

Human nail diseases, mostly caused by fungal infections, are common and difficult to treat. The development and testing of new drugs and drug delivery systems for the treatment of nail diseases is often limited by the lack of human nail material for permeation studies. Animal material is frequently used, but there are only few comparative data on the human nail plate, and there is neither a standardized test design nor a nail bed analogue to study drug uptake into the nail. In this study, a new permeation device was developed for permeation studies, and the permeation behavior of three model substances on the human nail plate and a model membrane from the horse hoof was investigated. A linear correlation was found between drug uptake by the human nail plate and the uptake by the equine hoof. The developed and established permeation device is suitable for investigations of ungual drug transport and enables the use of different membrane diameters and the use of a gel-based nail bed analog. The hydrogel-based acceptor medium used ensures adequate stabilization and hydration of the nail membrane. Full article

Background: Onychomycosis numbers among the most common fungal infections in humans affecting finger- or toenails. Histology remains a frequently applied screening technique to diagnose onychomycosis. Screening slides for fungal elements can be time-consuming for pathologists, and sensitivity in cases with low amounts of fungi remains a concern. Convolutional neural networks (CNNs) have revolutionized image classification in recent years. The goal of our project was to evaluate if a U-NET-based segmentation approach as a subcategory of CNNs can be applied to detect fungal elements on digitized histologic sections of human nail specimens and to compare it with the performance of 11 board-certified dermatopathologists. Methods: In total, 664 corresponding H&E- and PAS-stained histologic whole-slide images (WSIs) of human nail plates from four different laboratories were digitized. Histologic structures were manually annotated. A U-NET image segmentation model was trained for binary segmentation on the dataset generated by annotated slides. Results: The U-NET algorithm detected 90.5% of WSIs with fungi, demonstrating a comparable sensitivity with that of the 11 board-certified dermatopathologists (sensitivity of 89.2%). Conclusions: Our results demonstrate that machine-learning-based algorithms applied to real-world clinical cases can produce comparable sensitivities to human pathologists. Our established U-NET may be used as a supportive diagnostic tool to preselect possible slides with fungal elements. Slides where fungal elements are indicated by our U-NET should be reevaluated by the pathologist to confirm or refute the diagnosis of onychomycosis. Full article

Nail fungal infection is often mistakenly considered a minor issue or a purely esthetic problem that is not worth solving. However, onychomycosis has been demonstrated to have a negative impact on a patient’s social life. Therefore, given the poor efficacy of various therapy types, there is strong interest in exploring new methods for evaluating antifungal treatments. As such, the aim of this work was to develop a new protocol, using bovine hoof membranes as a model of the human nail to evaluate the capability of a product claiming to prevent fungal adhesion, which is the first step of the infection. In this work, two specific and representative fungal strains, Trichophyton rubrum and Candida albicans, were used. In order to evaluate the possible protective activity of a product against fungal contamination of the nail plate, it was first necessary to test the affinity of the hoof membranes to be contaminated by the fungi. Then, a pharmaceutical product and a base coat were tested as a positive and negative control, respectively, by introducing the membranes (anti-fungal, basic or no treatment and single vs. multiple treatments) into the fungal suspensions for three different contact times (15 min, 5 h and 24 h). The results showed that the more significant antiadhesive effect (AE) was obtained against Trichophyton rubrum than against Candida albicans. Furthermore, taking into account the results obtained at all testing times, 5 h appeared to be the best time for testing the antiadhesive activity. The results obtained after three treatments with drugs and on washed membranes, in comparison to one single application of antifungal product (AP), demonstrated clearly that the drug was able to penetrate deeper into the membranes to exert itself, even after washing and also after only 15 min of contact. Thus, hoof membrane has been shown to be a valuable in vitro model for this kind of product assessment. Full article

Plate or nail fixations have been applied to the repair of clavicle fractures. However, it is quite difficult to fairly evaluate the different clavicle fixation techniques owing to variations in the bone anatomy, bone quality, and fracture pattern. The purpose of this study was to investigate the biomechanical performances of different fixation techniques applied to a clavicle fracture using the finite element method. A simplified single-clavicle model and a complete human upper-body skeleton model were developed in this study. Three types of plate fixations, namely, superior clavicle plate, anterior clavicle plate, and clavicle anatomic spiral fixations, and one nail fixation, a titanium elastic nail fixation, were investigated and compared. The plate fixation techniques have a better fixation stability compared to the nail fixation technique. However, the nail fixation technique shows lower bone stress and can reduce the risk of a peri-implant fracture compared to the plate fixation techniques. Increasing the number of locking screws for the clavicle plate system can reduce the implant stress. Insertion of the bone plate into the anterior site of the clavicle or a multi-plane fixation is recommended to achieve the required biomechanical performance. A plate fixation revealed a relatively better fixation stability, and a nail fixation showed a lower risk of a peri-implant fracture. Full article

Difficulties in obtaining human nails that are large enough for examining the penetration of drug formulations led us to produce keratin films regenerated from human hair. We assume that these films can simulate human nail plates in drug penetration and permeation tests and can serve as a biological model for studying onychomycosis. The films were formed from keratin extracted from human hair using dithiothreitol, urea and thiourea. The obtained keratin extract was dispensed into Teflon rings and dried at 40 °C and then cured at 110 °C. The structure, surface morphology, chemical characterization and thermal stability of the films were characterized and were compared to those of human nail, hair and bovine hoof samples using SDS-electrophoresis, scanning electron microscopy (SEM), X-ray diffraction analysis (XRD), Fourier transform infrared spectroscopy (FTIR) and thermogravimetric analysis (TGA). The structure of the obtained films was found to be closer to human nails than to hair or bovine hooves. The keratin films were infected with Trichophyton rubrum and were proven to be appropriate for serving as a model for studying onychomycosis. Full article

A deteriorating nail standard is a growing problem as the global prevalence of diabetes is increasing. Systemic treatment with mineral supplements may not be recommended, mainly due to the high doses required to deliver optimal therapeutic concentrations. In this work, we evaluate nail polish formulations for the local delivery of strengthening elements to the nail plate. Specifically, we assess calcium and silicon release from nail polish base coat formulations containing three different concentrations of White Portland Cement to water, as well as to artificial and human nails. The delivery of calcium and silicon to the dorsal nail plate was determined by inductively coupled plasma optical emission spectrometry, scanning electron microscopy, and energy dispersive X-ray spectroscopy. To the best of our knowledge, this is the first study showing that such dual elemental delivery to human nails can be achieved from nail polish formulations. Hence, this work may form the basis for new inventions where therapeutic functionalities can be integrated with the mechanical and cosmetic properties of a base coat nail polish. Future permeability studies are required to verify long-term effects on the nail standard, induced by the formulations under study. Full article

In vitro permeation studies using nail clippings or nail plates are commonly used in the development of transungual formulations. However, there are ethical, safety and cost issues associated with sourcing such tissues. Herein, we describe a preliminary approach is described for the design and manufacture of a human nail model surrogate based on 3D printing. To evaluate these 3D printed constructs, nails were mounted in conventional glass Franz cells and a commercial antifungal lacquer formulation containing ciclopirox olamine was applied daily to the surrogate printed surfaces for a period of 14 days. On days 8 and 14, the surfaces of the 3D printed nails were washed with ethanol to remove excess formulation. Confocal Raman spectroscopy (CRS) was used to profile the drug in the 3D printed nail. At the end of the Franz cell studies, no drug was observed in the receptor phase. CRS studies confirmed penetration of the active into the model nails with reproducible depth profiles. Our ongoing work is focused on synthesising commercial and non-commercial printable resins that can replicate the physical and chemical characteristics of the human nail. This will allow further evaluation of actives for ungual therapy and advance the development of the surrogate nail tissue model. Full article

Topical monotherapy of nail infection is limited by poor drug permeability into the human nail plate. Numerous substances and methods are applied to improve the antifungal agent delivery across the nail plate. This work aimed to evaluate the effect of chemical and physical enhancers on the accumulation and permeation of amorolfine hydrochloride through human nail clippings. Polymeric nail lacquers with Eudragit E100 were developed as a potentially suitable delivery system for amorolfine hydrochloride. Incorporating thioglycolic acid and urea into formulations provided increased accumulation of antifungal agent in nail layers of up to 100% and 57%, respectively. Structural changes of nail barrier, induced by fractional CO₂ laser, were visualized by microscopy. The permeation of amorolfine hydrochloride through the nail increased twofold when thioglycolic acid-containing formulation was applied and the nail was pretreated with a fractional CO₂ laser. The results suggest that this novel combination of enhancers has the potential to be an effective option for topical drug delivery through the nail, and increased the efficacy of treatment. Full article

Lack of standardization of clinically compliant culture protocols of mesenchymal stem cells for re-implantation in humans have hindered clinical progress in the field of tissue regeneration to repair maxillofacial and orthopedic defects. The goal of this study was to establish a clinically relevant osteogenic protocol for collection and expansion of autologous stem cells to be used at Marshall University for re-implantation and repair of maxillofacial and orthopedic conditions. Human bone marrow (hBM) samples were collected from patients undergoing intramedullary nail fixation for closed femoral fractures. hBM mesenchymal cells were expanded by growing them first in Petri dishes for two weeks, followed by a week of culture using Perfecta 3D Hanging Drop Plates^®. Various scaffold materials were tested and analyzed for cellular integration, vitality, and differentiation capacity of harvested hBM-MSCs including: 60/40 blend of hydroxyapatite biomatrix; Acellular bone composite discs; Allowash^®, cancellous bone cubes; PLGA (poly lactic-co-glycolic acid); and Woven chitin derived fiber. We found that the 3D spheroid culture allowed production of hBM mesenchymal cells that retained osteoblast differentiation capacity over a monolayer culture of hBM-MSCs without the need to use chemical or hormonal modulation. We also observed that hydroxyapatite and Allowash cancellous bone scaffolds allowed better cell integration and viability properties as compared to other materials tested in this study. In conclusion, the multimodal culture methodology we developed creates actively differentiating stem-cell spheroids that can then be readily utilized in clinical practices to improve the regeneration of tissues of the head and the body. Full article

Onychomycosis is a fungal infection of nails that is widespread and difficult to treat because of the impermeable nature of human nails. Topically applied anti-fungal agents cannot penetrate this structure, and treatment regimens often resort to systemic antifungals with concomitant side effects. One recent clinical study suggested that mechanical fenestration of the nail using an intelligent nail drill might be a possible solution to this problem. In this work, an in vitro model of the transungual delivery of antifungal agents is presented, which utilizes real nail tissue and an inline flow system. This system was deployed to measure transungual delivery of ciclopirox and determined that nail fenestration improved drug delivery by 3–4-fold after 42 days. This study bolsters the argument that nail fenestration should be accepted as a pretreatment for onychomycosis and offers a way of evaluating new drugs or formulations designed to combat this condition. Full article

Onychomycosis is predominantly caused by the dermatophytes Trichophyton rubrum, Trichophyton mentagrophytes and Trichophyton tonsurans. The main treatment obstacle concerns low nail-plate drug permeability. In vitro antifungal photodynamic treatment (PDT) and nail penetration enhancing effectiveness have been proven for multifunctional photosensitizer 5,10,15-tris(4-N-methylpyridinium)-20-(4-(butyramido-methylcysteinyl)-hydroxyphenyl)-[21H,23H]-porphine trichloride (PORTHE). This study investigates single PORTHE green laser/LED PDT of varying degrees of ex vivo onychomycoses in a human nail model. T. mentagrophytes, T. rubrum, T. tonsurans onychomycoses were ex vivo induced on nail pieces at 28 °C (normal air) and 37 °C (6.4% CO₂) during 3 to 35 days and PDTs applied to the 37 °C infections. All dermatophytes showed increasingly nail plate invasion at 37 °C between 7 and 35 days; arthroconidia were observed after 35 days for T. mentagrophytes and T. tonsurans. Using 81 J/cm² (532 nm) 7-day T. mentagrophytes onychomycoses were cured (92%) with 80 µM PORTHE (pH 8) after 24 h propylene glycol (PG, 40%) pre-treatment and 35-day onychomycoses (52%–67%) with 24 h PORTHE (40–80 µM)/40% PG treatment (pH 5). 28 J/cm² LED light (525 ± 37 nm) improved cure rates to 72%, 83% and 73% for, respectively, T. mentagrophytus, T. rubrum and T. tonsurans 35-day onychomycoses and to 100% after double PDT. Data indicate PDT relevance for onychomycosis. Full article