Search

Surface texturing is widely investigated for the modulation of the surface properties and biological response of implantable materials. Laser is a green technology for the obtainment of specific patterns without the employment of toxic chemicals. In the present research, a picosecond laser treatment was applied to commercially pure titanium and Ti6Al4V alloy for the obtainment of aligned grooves characterized by micrometric width and spacing but submicrometric depth to promote fibroblast alignment and discourage bacterial adhesion. Surface topography and roughness of laser-textured surfaces were characterized using confocal microscopy, contact profiler, and Scanning Electron Microscopy. Zeta potential titration curves and contact angle measurements were used for the investigation of surface charge and wettability, while X-Ray Diffraction was employed for crystallographic characterization. Finally, the biological response (fibroblast adhesion and alignment and bacterial adhesion) was assessed. Similar results were obtained on commercially pure Ti and Ti6Al4V. Grooves with the designed features were obtained (about 15 μm spaced and 0.2μ deep) and the treated surfaces had a complex micro- and nano-scale morphology which reduced wettability. No evident chemical modification occurred. The treated surfaces were biocompatible and grooves had a contact guidance effect on human fibroblasts. The obtained topography had anti-adhesive action on bacteria (Staphylococcus aureus).

Globally, northern peatlands are major carbon deposits with important implications for the climate system. It is therefore crucial to understand their spatial occurrence, especially in the context of peatland degradation by land cover change and climate change. This study was aimed at mapping peatlands in the forested landscape of Sweden by modelling soil data against lidar-based terrain indices. Machine learning methods were used to produce nationwide raster maps at 10 m spatial resolution indicating the presence or not of peatlands. Four different definitions of peatlands were examined: 30, 40, 50 and 100 cm thickness of the organic horizon. Depending on peatland definition, testing with a hold-out dataset indicated an accuracy of 0.89–0.91 and Matthew's correlation coefficient of 0.79–0.81. The final maps showed a national forest peatland extent of 60 292–71 996 km2, estimates which are in the range of previous studies employing traditional soil maps. In conclusion, these results emphasize the possibilities of mapping boreal peatlands with lidar-based terrain indices. The final peatland maps are publicly available at https://doi.org/10.17043/rimondini-2023-peatlands-2 (Rimondini et al., 2023) and may be employed for spatial planning, estimating carbon stocks and evaluating climate change mitigation strategies.

This paper contains original data supporting the antibacterial activities of Gallium (Ga3+)-doped pro-osteointegrative titanium alloys, obtained via Anodic Spark Deposition (ASD), as described in “The effect of silver or gallium doped titanium against the multidrug resistant Acinetobacter baumannii” (Cochis et al. 2016) [1].In this article we included an indirect cytocompatibility evaluation towards Saos2 human osteoblasts and extended the microbial evaluation of the Ga3+ enriched titanium surfaces against the biofilm former Escherichia coli and Staphylococcus epidermidis strains. Cell viability was assayed by the Alamar Blue test, while bacterial viability was evaluated by the metabolic colorimetric 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay. Finally biofilm morphology was analyzed by Scanning Electron Microscopy (SEM). Data regarding Ga3+ activity were compared to Silver. Keywords: E. coli, S. epidermidis, Biofilm, Gallium, Silver, Titanium, Anodic Spark Deposition

Mesoporous bioactive glass nanoparticles (MBGNs) doped with therapeutical ions present multifunctional systems that enable a synergistic outcome through the dual delivery of drugs and ions. The aim of this study was to evaluate influence of co-doping with strontium and magnesium ions (SrMg-MBGNs) on the properties of MBGNs. A modified microemulsion-assisted sol-gel synthesis was used to obtain particles, and their physicochemical properties, bioactivity, and drug-loading/release ability were evaluated. Indirect biological assays using 2D and 3D cell culture models on human bone marrow-derived mesenchymal stem cells (hBM-MSCs) and endothelial EA.hy926 cells, respectively, were used to determine biocompatibility of MBGNs, their influence on alkaline phosphatase (ALP) production, calcium deposition, and cytoskeletal organization. Results showed that Sr,Mg-doping increased pore volume and solubility, and changed the mesoporous structure from worm-like to radial-dendritic, which led to a slightly accelerated drug release compared to pristine MBGNs. Biological assays confirmed that particles are biocompatible, and have ability to slightly induce ALP production and calcium deposition of hBM-MSCs, as well as to significantly improve the proliferation of EA.hy926 compared to biochemical stimulation via vascular endothelial growth factor (VEGF) administration or regular media. Fluorescence staining revealed that SrMg-MBGNs had a similar effect on EA.hy926 cytoskeletal organization to the VEGF group. In conclusion, Sr,Mg-MBGNs might be considered promising biomaterial for biomedical applications.

This study evaluates the cytocompatibility of cerium-doped mesoporous bioactive glasses (Ce-MBGs) loaded with polyphenols (Ce-MBGs-Poly) for possible application in bone tissue engineering after tumour resection. We tested MBGs powders and pellets on 2D and 3D in vitro models using human bone marrow-derived mesenchymal stem cells (hMSCs), osteosarcoma cells (U2OS), and endothelial cells (EA.hy926). Promisingly, at a low concentration in culture medium, Poly-loaded MBGs powders containing 1.2 mol% of cerium inhibited U2OS metabolic activity, preserved hMSCs viability, and had no adverse effects on EA.hy926 migration. Moreover, the study discussed the possible interaction between cerium and Poly, influencing anti-cancer effects. In summary, this research provides insights into the complex interactions between Ce-MBGs, Poly, and various cell types in distinct 2D and 3D in vitro models, highlighting the potential of loaded Ce-MBGs for post-resection bone tissue engineering with a balance between pro-regenerative and anti-tumorigenic activities., Competing Interests: The authors do not have any conflicts of interest to declare., (© 2024 The Author(s).)

Proteomic analysis of extracellular vesicles presents several challenges due to the unique nature of these small membrane-bound structures. Alternative analyses could reveal outcomes hidden from standard statistics to explore and develop potential new biological hypotheses that may have been overlooked during the initial evaluation of the data. An analysis sequence focusing on deviating protein expressions from donors' primary cells was performed, leveraging machine-learning techniques to analyze small datasets, and it has been applied to evaluate extracellular vesicles' protein content gathered from mesenchymal stem cells cultured on bioactive glass discs doped or not with metal ions. The goal was to provide additional opportunities for detecting details between experimental conditions that are not entirely revealed with classic statistical inference, offering further insights regarding the experimental design and assisting the researchers in interpreting the outcomes. The methodology extracted a set of EV-related proteins whose differences between conditions could be partially explainable with statistics, suggesting the presence of other factors involved in the bioactive glasses' interactions with tissues. Outlier identification of extracellular vesicles' protein expression levels related to biomaterial preparation was instrumental in improving the interpretation of the experimental outcomes.

The present manuscript tested an automated analysis sequence to provide a decision support system to track the OCP synthesis from [Formula: see text]-TCP over time. Initially, the XRD and FTIR signals from a hundredfold scaled-up hydrolysis of OCP from [Formula: see text]-TCP were fused and modeled by the curve fitting based on the significantly established maxima from the literature and nine features extracted from the fitted shapes. Afterward, the analysis sequence enclosed the machine learning techniques for feature ranking, spatial filtering, and dimensionality reduction to support the automatic recognition of the synthesis stages. The proposed analysis pipeline for OCP identification might be the foundation for a decision support system explicitly targeting OCP synthesis. Future projects will exploit the suggested methodology for pinpointing the OCP production over time (including the intermediary phases present in the OCP formation) and for evaluating whether biological variables might be merged with biomaterial properties to build a unified model of tissue response to the implant., (© 2024. The Author(s).)

In recent years, antimicrobial peptides (AMPs) have attracted great interest in scientific research, especially for biomedical applications such as drug delivery and orthopedic applications. Since they are readily degradable in the physiological environment, scientific research has recently been trying to make AMPs more stable. Peptoids are synthetic N-substituted glycine oligomers that mimic the structure of peptides. They have a structure that does not allow proteolytic degradation, which makes them more stable while maintaining microbial activity. This structure also brings many advantages to the molecule, such as greater diversity and specificity, making it more suitable for biological applications. For the first time, a synthesized peptoid (GN2-Npm 9 ) was used to functionalize a nanometric chemically pre-treated (CT) titanium surface for bone-contact implant applications. A preliminary characterization of the functionalized surfaces was performed using the contact angle measurements and zeta potential titration curves. These preliminary analyses confirmed the presence of the peptoid and its adsorption on CT. The functionalized surface had a hydrophilic behaviour (contact angle = 30°) but the hydrophobic tryptophan-like residues were also exposed. An electrostatic interaction between the lysine residue of GN2-Npm 9 and the surface allowed a chemisorption mechanism. The biological characterization of the CT_GN2-Nmp 9 surfaces demonstrated the ability to prevent surface colonization and biofilm formation by the pathogens Escherichia coli and Staphylococcus epidermidis thus showing a broad-range activity. The cytocompatibility was confirmed by human mesenchymal stem cells. Finally, a bacteria-cells co-culture model was applied to demonstrate the selective bioactivity of the CT_GN2-Nmp 9 surface that was able to preserve colonizing cells adhered to the device surface from bacterial infection., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier Ltd.)

Prosthetic liners are mainly used as an interface between residual limbs and prosthetic sockets to minimize physical and biological damage to soft tissue. However, the closed and moist conditions within liners and the amputee's skin provide a suitable environment for bacterial growth to cause infections. This study aimed to coat a comprehensive variant material with copper oxide nanoparticles (CuO NPs) and compare their surface analysis and antibacterial properties. These materials were covered with CuO NPs solution at a concentration of 70 μg mL -1 to achieve this purpose. After drying, their surface characteristics were analyzed by measuring zeta potential, contact angle, surface roughness, and fiber arrangement. Cu-released concentration from the coatings into the acetate buffer solution by inductively coupled plasma mass spectrometry indicated that lycra and nylon quickly released Cu ions to concentrations up to ∼0.2 μg mL -1 after 24 h, causing low metabolic activity of human bone-marrow mesenchymal stem cells (bMSC) in the indirect assay. Antibacterial activity of the coated specimens was evaluated by infecting their surfaces with the Gram-positive bacteria Staphylococcus epidermidis, reporting a significant ∼40 % reduction of metabolic activity for x-dry after 24 h; in addition, the number of viable bacterial colonies adhered to the surface of this material was reduced by ∼23 times in comparison with non-treated x-dry that were visually confirmed by scanning electron microscope. In conclusion, CuO NPs x-dry shows optimistic results to pursue further experiments due to its slow speed of Cu release and prolonged antibacterial activity, as well as its compatibility with human cells., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 Published by Elsevier Ltd.)

The regeneration of large bone defects is still demanding, requiring biocompatible scaffolds, with osteoconductive and osteoinductive properties. This study aimed to assess the pre-clinical efficacy of a nano-hydroxyapatite (nano-HA)/PGLA/dextran-based scaffold loaded with Polylevolysine (PLL) and fibronectin (FN), intended for bone regeneration of a critical-size tibial defect, using an ovine model. After physicochemical characterization, the scaffolds were implanted in vivo, producing two monocortical defects on both tibiae of ten adult sheep, randomly divided into two groups to be euthanized at three and six months after surgery. The proximal left and right defects were filled, respectively, with the test scaffold (nano-HA/PGLA/dextran-based scaffold loaded with PLL and FN) and the control scaffold (nano-HA/PGLA/dextran-based scaffold not loaded with PLL and FN); the distal defects were considered negative control sites, not receiving any scaffold. Histological and histomorphometric analyses were performed to quantify the bone ingrowth and residual material 3 and 6 months after surgery. In both scaffolds, the morphological analyses, at the SEM, revealed the presence of submicrometric crystals on the surfaces and within the scaffolds, while optical microscopy showed a macroscopic 3D porous architecture. XRD confirmed the presence of nano-HA with a high level of crystallinity degree. At the histological and histomorphometric evaluation, new bone formation and residual biomaterial were detectable inside the defects 3 months after intervention, without differences between the scaffolds. At 6 months, the regenerated bone was significantly higher in the defects filled with the test scaffold (loaded with PLL and FN) than in those filled with the control scaffold, while the residual material was higher in correspondence to the control scaffold. Nano-HA/PGLA/dextran-based scaffolds loaded with PLL and FN appear promising in promoting bone regeneration in critical-size defects, showing balanced regenerative and resorbable properties to support new bone deposition.

Spiking neural networks are biologically inspired machine learning algorithms attracting researchers' attention for their applicability to alternative energy-efficient hardware other than traditional computers. In the current work, spiking neural networks have been tested in a quantitative structure-activity analysis targeting the toxicity of molecules. Multiple public-domain databases of compounds have been evaluated with spiking neural networks, achieving accuracies compatible with high-quality frameworks presented in the previous literature. The numerical experiments also included an analysis of hyperparameters and tested the spiking neural networks on molecular fingerprints of different lengths. Proposing alternatives to traditional software and hardware for time- and resource-consuming tasks, such as those found in chemoinformatics, may open the door to new research and improvements in the field.

The main unmet medical need of bone implants is multifunctional activity, including their ability to induce rapid and physiological osseointegration, counteract bacterial biofilm formation, and prevent in situ chronic inflammation at the same time. This research starts from an already developed c.p. titanium surface with proven bioactive (in vitro hydroxyl apatite precipitation) and antibacterial activities, due to a calcium titanate layer with nano- and micro-scale roughness and loaded with iodine ions. Here, antioxidant ability was added to prevent chronic inflammation by grafting polyphenols of a green tea extract onto the surface, without compromising the other functionalities of the surface. The surface was characterized before and after functionalization through XPS analysis, zeta potential titrations, ion release measurements, in vitro bioactivity tests, SEM and fluorescence microscopy, and Folin-Ciocalteu and biological tests. The presence of grafted polyphenols as a homogeneous layer was proven. The grafted polyphenols maintained their antioxidant ability and were anchored to the surface through the linking action of Ca 2+ ions added to the functionalizing solution. Iodine ion release, cytocompatibility towards human mesenchymal stem cells (hMSC), and antibacterial activity were maintained even after functionalization. The antioxidant ability of the functionalized surface was effective in preserving hMSC viability in a chemically induced pro-inflammatory environment, thus showing a scavenger activity towards toxic active species responsible for inflammation.

Strawberries and raspberries are susceptible to physiological and biological damage. Due to the consumer concern about using pesticides to control fruit rot, recent attention has been drawn to essential oils. Microbiological activity evaluations of different concentrations of tested EOs (cinnamon, clove, bergamot, rosemary and lemon; 10% DMSO-PBS solution was used as a diluent) against fruit rot fungal strains and a fruit-born human pathogen ( Escherichia coli ) indicated that the highest inhibition halos was found for pure cinnamon and clove oils; according to GC-MS analysis, these activities were due to the high level of the bioactive compounds cinnamaldehyde (54.5%) in cinnamon oil and eugenol (83%) in clove oil. Moreover, thermogravimetric evaluation showed they were thermally stable, with temperature peak of 232.0 °C for cinnamon and 200.6/234.9 °C for clove oils. Antibacterial activity evaluations of all tested EOs at concentrations from 5-50% ( v / v ) revealed a concentration of 10% ( v / v ) to be the minimum inhibitory concentration and minimum bactericidal concentration. The physicochemical analysis of fruits in an in vivo assay indicated that used filter papers doped with 10% ( v / v ) of cinnamon oil (stuck into the lids of plastic containers) were able to increase the total polyphenols and antioxidant activity in strawberries after four days, with it being easier to preserve strawberries than raspberries.

Background: Breast cancer-related lymphedema (BCRL) could be one consequence of breast cancer (BC). Although several risk factors have been identified, a predictive algorithm still needs to be made available to determine the patient's risk from an ensemble of clinical variables. Therefore, this study aimed to characterize the risk of BCRL by investigating the characteristics of autogenerated clusters of patients. Methods: The dataset under analysis was a multi-centric data collection of twenty-three clinical features from patients undergoing axillary dissection for BC and presenting BCRL or not. The patients' variables were initially analyzed separately in two low-dimensional embeddings. Afterward, the two models were merged in a bi-dimensional prognostic map, with patients categorized into three clusters using a Gaussian mixture model. Results: The prognostic map represented the medical records of 294 women (mean age: 59.823±12.879 years) grouped into three clusters with a different proportion of subjects affected by BCRL (probability that a patient with BCRL belonged to Cluster A: 5.71%; Cluster B: 71.42%; Cluster C: 22.86%). The investigation evaluated intra- and inter-cluster factors and identified a subset of clinical variables meaningful in determining cluster membership and significantly associated with BCRL biological hazard. Conclusions: The results of this study provide potential insight for precise risk assessment of patients affected by BCRL, with implications in prevention strategies, for instance, focusing the resources on identifying patients at higher risk.

Implant-associated infections are a severe global concern, especially in the case of orthopedic implants intended for long-term or permanent use. The traditional treatment through systemic antibiotic administration is often inefficient due to biofilm formation, and concerns regarding the development of highly resistant bacteria. Therefore, there is an unfulfilled need for antibiotic-free alternatives that could simultaneously support bone regeneration and prevent bacterial infection. This study aimed to perform, optimize, and characterize the surface functionalization of Ti6Al4V-ELI discs by an FDA-approved antimicrobial peptide, nisin, known to hold a broad antibacterial spectrum. Accordingly, nisin bioactivity was also evaluated by in vitro release tests both in physiological and inflammatory pH conditions. Several methods, such as X-ray photoelectron spectroscopy (XPS), and Kelvin Probe atomic force microscopy confirmed the presence of a physisorbed nisin layer on the alloy surface. The functionalization performed at pH 6-7 was found to be especially effective due to the nisin configuration exposing its hydrophobic tail outwards, which is also responsible for its antimicrobial action. In addition, the first evidence of gradual nisin release both in physiological and inflammatory conditions was obtained: the static contact angle becomes half of the starting one after 7 days of soaking on the functionalized sample, while it becomes 0° on the control samples. Finally, the evaluation of the antibacterial performance toward the pathogen Staphylococcus aureus after 24 h of inoculation showed the ability of nisin adsorbed at pH 6 to prevent bacterial microfouling into biofilm-like aggregates in comparison with the uncoated specimens: viable bacterial colonies showed a reduction of about 40% with respect to the un-functionalized surface and the formation of (microcolonies (biofilm-like aggregates) is strongly affected.

Introduction: Bladder cancer assessment with non-invasive gene expression signatures facilitates the detection of patients at risk and surveillance of their status, bypassing the discomforts given by cystoscopy. To achieve accurate cancer estimation, analysis pipelines for gene expression data (GED) may integrate a sequence of several machine learning and bio-statistical techniques to model complex characteristics of pathological patterns., Methods: Numerical experiments tested the combination of GED preprocessing by discretization with tree ensemble embeddings and nonlinear dimensionality reductions to categorize oncological patients comprehensively. Modeling aimed to identify tumor stage and distinguish survival outcomes in two situations: complete and partial data embedding. This latter experimental condition simulates the addition of new patients to an existing model for rapid monitoring of disease progression. Machine learning procedures were employed to identify the most relevant genes involved in patient prognosis and test the performance of preprocessed GED compared to untransformed data in predicting patient conditions., Results: Data embedding paired with dimensionality reduction produced prognostic maps with well-defined clusters of patients, suitable for medical decision support. A second experiment simulated the addition of new patients to an existing model (partial data embedding): Uniform Manifold Approximation and Projection (UMAP) methodology with uniform data discretization led to better outcomes than other analyzed pipelines. Further exploration of parameter space for UMAP and t-distributed stochastic neighbor embedding (t-SNE) underlined the importance of tuning a higher number of parameters for UMAP rather than t-SNE. Moreover, two different machine learning experiments identified a group of genes valuable for partitioning patients (gene relevance analysis) and showed the higher precision obtained by preprocessed data in predicting tumor outcomes for cancer stage and survival rate (six classes prediction)., Conclusions: The present investigation proposed new analysis pipelines for disease outcome modeling from bladder cancer-related biomarkers. Complete and partial data embedding experiments suggested that pipelines employing UMAP had a more accurate predictive ability, supporting the recent literature trends on this methodology. However, it was also found that several UMAP parameters influence experimental results, therefore deriving a recommendation for researchers to pay attention to this aspect of the UMAP technique. Machine learning procedures further demonstrated the effectiveness of the proposed preprocessing in predicting patients' conditions and determined a sub-group of biomarkers significant for forecasting bladder cancer prognosis., (© 2022. The Author(s).)

In bone tissue engineering research, bioreactors designed for replicating the main features of the complex native environment represent powerful investigation tools. Moreover, when equipped with automation, their use allows reducing user intervention and dependence, increasing reproducibility and the overall quality of the culture process. In this study, an automated uni-/bi-directional perfusion bioreactor combinable with pulsed electromagnetic field (PEMF) stimulation for culturing 3D bone tissue models is proposed. A user-friendly control unit automates the perfusion, minimizing the user dependency. Computational fluid dynamics simulations supported the culture chamber design and allowed the estimation of the shear stress values within the construct. Electromagnetic field simulations demonstrated that, in case of combination with a PEMF stimulator, the construct can be exposed to uniform magnetic fields. Preliminary biological tests on 3D bone tissue models showed that perfusion promotes the release of the early differentiation marker alkaline phosphatase. The histological analysis confirmed that perfusion favors cells to deposit more extracellular matrix (ECM) with respect to the static culture and revealed that bi-directional perfusion better promotes ECM deposition across the construct with respect to uni-directional perfusion. Lastly, the Real-time PCR results of 3D bone tissue models cultured under bi-directional perfusion without and with PEMF stimulation revealed that the only perfusion induced a ~ 40-fold up-regulation of the expression of the osteogenic gene collagen type I with respect to the static control, while a ~ 80-fold up-regulation was measured when perfusion was combined with PEMF stimulation, indicating a positive synergic pro-osteogenic effect of combined physical stimulations., (© 2022. The Author(s).)

This paper envisions Ti 40 Zr 10 Cu 36 Pd 14 bulk metallic glass as an oral implant material and evaluates its antibacterial performance in the inhabitation of oral biofilm formation in comparison with the gold standard Ti-6Al-4V implant material. Metallic glasses are superior in terms of biocorrosion and have a reduced stress shielding effect compared with their crystalline counterparts. Dynamic mechanical and thermal expansion analyses on Ti 40 Zr 10 Cu 36 Pd 14 show that these materials can be thermomechanically shaped into implants. Static water contact angle measurement on samples' surface shows an increased surface wettability on the Ti-6Al-4V surface after 48 ​h incubation in the water while the contact angle remains constant for Ti 40 Zr 10 Cu 36 Pd 14 . Further, high-resolution transmission and scanning transmission electron microscopy analysis have revealed that Ti 40 Zr 10 Cu 36 Pd 14 interior is fully amorphous, while a 15 ​nm surface oxide is formed on its surface and assigned as copper oxide. Unlike titanium oxide formed on Ti-6Al-4V, copper oxide is hydrophobic, and its formation reduces surface wettability. Further surface analysis by X-ray photoelectron spectroscopy confirmed the presence of copper oxide on the surface. Metallic glasses cytocompatibility was first demonstrated towards human gingival fibroblasts, and then the antibacterial properties were verified towards the oral pathogen Aggregatibacter actinomycetemcomitans responsible for oral biofilm formation. After 24 ​h of direct infection, metallic glasses reported a >70% reduction of bacteria viability and the number of viable colonies was reduced by ∼8 times, as shown by the colony-forming unit count. Field emission scanning electron microscopy and fluorescent images confirmed the lower surface colonization of metallic glasses in comparison with controls. Finally, oral biofilm obtained from healthy volunteers was cultivated onto specimens' surface, and proteomics was applied to study the surface property impact on species composition within the oral plaque., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

In medicine, tridimensional scanning devices produce digital surfaces that replicate the bodies of patients, facilitating anthropometric measurement and limb volume quantification in pathological conditions. Free programs that address this task are not commonly found, with doctors mainly relying on proprietary software. This aspect brings reduced reproducibility of studies and evaluation of alternative measures. A software package made up of three programs has been developed and released together with supporting materials to enhance reproducibility and comparisons between medical centers. In this article, the functions of the programs and steps for volume assessment were introduced together with a pilot study for upper limb volume quantification. This initial experiment aimed to also verify the performance of digital volumes derived from the convex-hull gift-wrapping algorithm and the alternative analysis methods enclosed in the software. Few of these digital volumes are parameter-dependent, requiring a value selection. The experiment was conducted on a small mixed-gender group of young adults without correction for factors like arm dominance or specific physical training. In the sample under investigation, the analysis confirmed the substantial agreement between the clinical and current configurations of digital volumes produced by the package ( R 2 interval from 0.93 to 0.97, r ranged from 0.965 to 0.984); in addition, as a general consideration, gender appears as a variable that could influence upper limb volume quantification if a single model is built., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Nascimben, Lippi, Fusco, Invernizzi and Rimondini.)

Tissue regeneration is a hot topic in health sciences, particularly because effective therapies promoting the healing of several cell types are lacking, specifically those of the musculoskeletal system. Mesenchymal Stem/Stromal Cells (MSCs) have been identified as crucial players in bone homeostasis, and are considered a promising therapy for diseases such as osteoarthritis (OA) and Rheumatoid Arthritis (RA). However, some known drawbacks limit their use, particularly ethical issues and immunological rejections. Thus, MSCs byproducts, namely Extracellular Vesicles (EVs), are emerging as potential solutions to overcome some of the issues of the original cells. EVs can be modulated by either cellular preconditioning or vesicle engineering, and thus represent a plastic tool to be implemented in regenerative medicine. Further, the use of biomaterials is important to improve EV delivery and indirectly to modulate their content and secretion. This review aims to connect the dots among MSCs, EVs, and biomaterials, in the context of musculoskeletal diseases.

Functional ability is the basis of healthy aging. Articular cartilage degeneration is amongst the most prevalent degenerative conditions that cause adverse impacts on the quality of life; moreover, it represents a key predisposing factor to osteoarthritis (OA). Both the poor capacity of articular cartilage for self-repair and the unsatisfactory outcomes of available clinical interventions make innovative tissue engineering a promising therapeutic strategy for articular cartilage repair. Significant progress was made in this field; however, a marked heterogeneity in the applied biomaterials, biofabrication, and assessments is nowadays evident by the huge number of research studies published to date. Accordingly, this literature review assimilates the most recent advances in cell-based and cell-free tissue engineering of articular cartilage and also focuses on the assessments performed via various in vitro studies, ex vivo models, preclinical in vivo animal models, and clinical studies in order to provide a broad overview of the latest findings and clinical translation in the context of degenerated articular cartilage and OA.

Zirconium-Copper-based metallic glass thin films represent promising coatings in the biomedical sector for their combination of antibacterial property and wear resistance. However, finding a Zr-Cu metallic glass composition with desirable cytocompatibility and antibacterial property is extremely challenging. In this work, we have created a cytocompatible and (super-)hydrophobic Zr-Cu-Ag metallic glass coating with ≈95% antifouling properties. First, a range of different chemical compositions were prepared via Physical Vapor Deposition magnetron by co-sputtering Zr, Cu, and Ag onto a Polybutylene terephthalate (PBT) substrate among which Zr 93·5 Cu 6·2 Ag 0.2 , Zr 76·7 Cu 22·7 Ag 0.5, and Zr 69·3 Cu 30·1 Ag 0.6 were selected to be further investigate for their surface properties, antibacterial activity, and cytocompatibility. Scanning electron microscopy (SEM) images revealed a micro-roughness fibrous structure holding superhydrophobic properties demonstrated by specimens' static and dynamic contact angle measurements ranging from 130° to 150°. The dynamic contact angle measurements have shown hysteresis below 10° for all coated samples which indicated the superhydrophobicity of the samples. To distinguish between antifouling and bactericidal effect of the coating, ions release from coatings into Luria Bertani Broth (LB), and Dulbecco's Modified Eagle Medium (DMEM) solutions were evaluated by inductively coupled plasma mass spectrometry (ICP-MS) measurements after 24 ​h and 5 days. Antifouling properties were evaluated by infecting the specimens' surface with the Gram-positive Staphylococcus aureus and the Gram-negative Escherichia coli strain reporting a ≈95% reduction of bacteria adhesion as visually confirmed by FESEM and fluorescent live/dead staining. Human mesenchymal stem cells (hMSC) were used for direct cytocompatibility evaluation of coated samples and their metabolic activity was evaluated via relative fluorescence unit after 24 ​h and 5 days confirming that it was comparable to the controls (>97% viable cells). The results were further visualized by FESEM, fluorescent staining by Live/Dead Viability/Cytotoxicity Kit and confirmed the cytocompatibility of all coated samples. Finally, hMSC' cytoplasm was stained by May Grunwald and Giemsa after 5days to detect and visualize the released ions which have diffused through the cells' membrane., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Author(s).)

In vitro and in vivo studies are fundamental steps in the characterization of new implantable materials to preliminarily assess their biological response. The present study reports the in vitro and in vivo characterizations of a novel experimental silicate bioactive glass (BG) (47.5B, 47.5SiO 2 -10Na 2 O-10K 2 O-10MgO-20CaO-2.5P 2 O 5 mol.%). Cytocompatibility tests were performed using human mature osteoblasts (U2OS), human mesenchymal stem cells (hMSCs) and human endothelial cells (EA.hy926). The release of the early osteogenic alkaline phosphatase (ALP) marker suggested strong pro-osteogenic properties, as the amount was comparable between hMSCs cultivated onto BG surface and cells cultivated onto polystyrene control. Similarly, real-time PCR revealed that the osteogenic collagen I gene was overexpressed in cells cultivated onto BG surface without biochemical induction. Acute toxicity tests for the determination of the median lethal dose (LD 50 ) allowed classifying the analyzed material as a slightly toxic substance with LD 50 = 4522 ± 248 mg/kg. A statistically significant difference in bone formation was observed in vivo through comparing the control (untreated) group and the experimental one, proving a clear osteogenic effect induced by the implantation at the defect site. Complete resorption of 47.5B powder was observed after only 3 months in favor of newly formed tissue, thus confirming the high osteostimulatory potential of 47.5B glass.

Background and Aim of the Work: Magnesium (Mg) is a metal physiologically present in bone tissue and essential for bone health. Mg-based-alloys exhibit mechanical properties, namely density and strength, similar to human cortical bone. These features have been exploited for the development of osteosynthesis devices in biodegradable Mg-based-alloys. Accordingly, the aim of this study was to rank the effectiveness and safety of Mg-based alloys applied in bone surgery in comparison to other suitable metals, focusing in particular on Mg superior biocompatibility and biodegradability., Methods: a systematic-review of the literature was conducted including only primary research studies dealing with patients suffering from fractured or osteotomized bones fixed using Mg-based osteosynthesis-devices., Results: literature revision suggested Mg-alloys holding comparable properties and side effects in comparison with titanium (Ti) screws, thus showing similar efficacy and safety. In particular, the gas formation in the carpal bones was identified as the main side effect of the Mg-alloys, during the corrosion/degradation phase of Mg., Conclusions: according to the considered literature, the main advantages exploiting Mg-alloys for bone implants are related to their biocompatibility, bio-absorbability/-degradability, the lack of surgical removal, osteoconductivity and antibacterial activity. On the opposite, the main limitation of Mg-alloys is due to the poor mechanical resistance of small devices for internal fixation of bone fragments that lack of sufficient strength to withstand high forces. Therefore, an important future prospect could rely in the development of innovative hybrid systems aimed at fixing high load-bearing fractures, as well as in regenerative-medicine by developing new Mg-based engineered scaffolds.

Bioactive glass (BG) represents a promising biomaterial for bone healing; here injectable BG pastes biological properties were improved by the addition of gelatin or chitosan, as well as mechanical resistance was enhanced by adding 10 or 20 wt% 3-Glycidyloxypropyl trimethoxysilane (GPTMS) cross-linker. Composite pastes exhibited bioactivity as apatite formation was observed by Scanning Electron Microscopy (SEM) and X-Ray Diffraction (XRD) after 14 days immersion in simulated body fluid (SBF); moreover, polymers did not enhance degradability as weight loss was >10% after 30 days in physiological conditions. BG-gelatin-20 wt% GPTMS composites demonstrated the highest compressive strength (4.8 ± 0.5 MPa) in comparison with the bulk control paste made of 100% BG in water (1.9 ± 0.1 MPa). Cytocompatibility was demonstrated towards human mesenchymal stem cells (hMSC), osteoblasts progenitors, and endothelial cells. The presence of 20 wt% GPTMS conferred antibacterial properties thus inhibiting the joint pathogens Staphylococcus aureus and Staphylococcus epidermidis infection. Finally, hMSC osteogenesis was successfully supported in a 3D model as demonstrated by alkaline phosphatase release and osteogenic genes expression.

Electrospinning is gaining increasing interest in the biomedical field as an eco-friendly and economic technique for production of random and oriented polymeric fibers. The aim of this review was to give an overview of electrospinning potentialities in the production of fibers for biomedical applications with a focus on the possibility to combine biomechanical and topographical stimuli. In fact, selection of the polymer and the eventual surface modification of the fibers allow selection of the proper chemical/biological signal to be administered to the cells. Moreover, a proper design of fiber orientation, dimension, and topography can give the opportunity to drive cell growth also from a spatial standpoint. At this purpose, the review contains a first introduction on potentialities of electrospinning for the obtainment of random and oriented fibers both with synthetic and natural polymers. The biological phenomena which can be guided and promoted by fibers composition and topography are in depth investigated and discussed in the second section of the paper. Finally, the recent strategies developed in the scientific community for the realization of electrospun fibers and for their surface modification for biomedical application are presented and discussed in the last section.

Stainless steel implants are suitable candidates for bone replacement due to their cytocompatibility and mechanical resistance, but they suffer from lack of bioactivity and are prone to bacterial infections. Accordingly, to overcome those limitations, in this study we developed by electrophoretic deposition (EPD), an innovative surface coating made of (i) zein , a natural fibroblast-friendly polymer, (ii) bioactive glass , a pro-osteogenic inorganic material and (iii) copper containing bioactive glass , an antibacterial and pro-angiogenic material. FESEM images confirmed that porous, uniform and free of cracks coatings were obtained by EPD; moreover, coatings were resistant to mechanical stress as demonstrated by the tape test, resulting in a 4B classification of adhesion to the substrate. The coatings were cytocompatible as indicated by metabolism evaluation of human fibroblasts, endothelial cells and mature or progenitor osteoblasts cultivated in direct contact with the specimens. They also maintained pro-osteogenic properties towards undifferentiated progenitor cells that expressed osteogenic genes after 15 days of direct cultivation. Copper conferred antibacterial properties as biofilm formation of the joint pathogens Staphylococcus aureus, Staphylococcus epidermidis and Escherichia coli was significantly reduced in comparison with copper-free coatings (p < 0.05). Moreover, this anti-infective activity resulted as targeted towards bacteria while the cells viability was preserved when cells and bacteria were cultivated in the same environment by a co-culture assay. Finally, copper ability to recruit blood vessels and to inhibit bacterial infection was confirmed in vivo where the growth of S. aureus biofilm was inhibited and the formation of new (<50 μm diameter spread) blood vessels was observed., (© 2020 The Authors. Production and hosting by Elsevier B.V. on behalf of KeAi Communications Co., Ltd.)

Cartilage repair still represents a challenge for clinicians and only few effective therapies are nowadays available. In fact, surgery is limited by the tissue poor self-healing capacity while the autologous transplantation is often forsaken due to the poor in vitro expansion capacity of chondrocytes. Biomaterials science offers a unique alternative based on the replacement of the injured tissue with an artificial tissue-mimicking scaffold. However, the implantation surgical practices and the scaffold itself can be a source of bacterial infection that currently represents the first reason of implants failure due to the increasing antibiotics resistance of pathogens. So, alternative antibacterial tools to prevent infections and consequent device removal are urgently required. In this work, the role of Nisin and LL-37 peptides has been investigated as alternative to antibiotics to their antimicrobial performances for direct application at the surgical site or as doping chemicals for devices aimed at articular cartilage repair. First, peptides cytocompatibility was investigated toward human mesenchymal stem cells to determine safe concentrations; then, the broad-range antibacterial activity was verified toward the Gram-positive Staphylococcus aureus and Staphylococcus epidermidis as well as the Gram-negative Escherichia coli and Aggregatibacter actinomycetemcomitans pathogens. The peptides selective antibacterial activity was verified by a cells-bacteria co-culture assay, while chondrogenesis was assayed to exclude any interference within the differentiation route to simulate the tissue repair. In the next phase, the experiments were repeated by moving from the cell monolayer model to 3D cartilage-like spheroids to revisit the peptides activity in a more physiologically relevant environment model. Finally, the spheroid model was applied in a perfusion bioreactor to simulate an infection in the presence of circulating peptides within a physiological environment. Results suggested that 75 μg/ml Nisin can be considered as a very promising candidate since it was shown to be more cytocompatible and potent against the investigated bacteria than LL-37 in all the tested models., (Copyright © 2020 Najmi, Kumar, Scalia, Cochis, Obradovic, Grassi, Leigheb, Lamghari, Loinaz, Gracia and Rimondini.)

Background and Aim of the Work: Tibial plateau fractures include a wide spectrum of lesions with potentially disabling sequelae. Arthroscopically-assisted Reduction and Internal Fixation (ARIF) is an alternative to traditional ORIF. The aim of this retrospective single centre study is to evaluate medium-term clinical and radiographic outcomes achieved in a consecutive series of patients treated with ARIF., Methods: 21 patients, with a mean age of 52.2 ± 13.4 years at surgery, were included. According to Schatzker classification, there were 9 type II, 10 type III, 2 type IV fractures. Associated intra-articular injuries (meniscal tears, tibial spine fractures, chondral lesions) were detected in 8 patients. At follow up, patients were clinically and radiographically evaluated according to knee ROM, KOOS, OKS and Rasmussen Clinical and Radiological Scores., Results: At an average follow-up of 84 ± 22.5 months, 18 patients were evaluated. Mean values recorded were the following: knee ROM 1° - 135°, OKS 41.6 / 48 ± 8.18, subscale KOOS scores ranged from 75% ± 25.4 (Quality of Life) to 91.1% ± 11.2 (Pain), Rasmussen Clinical e Radiological 27.2 ± 2.64 (14 excellent, 3 good, 1 fair) and 9.1 ± 0.64 (15 excellent, 3 good) respectively. Worse results were observed in 5 patients with pre-existing degenerative chondropathy., Conclusions: ARIF revealed to be an effective technique for surgical treatment of unicondylar tibial plateau fractures. Our findings support the favourable results reported by other authors. ARIF is not a simple technique and requiresspecific experience in knee arthroscopy and a steep learning curve.(www.actabiomedica.it).

Bacterial infections represent nowadays the major reason of biomaterials implant failure, however, most of the available implantable materials do not hold antimicrobial properties, thus requiring antibiotic therapy once the infection occurs. The fast raising of antibiotic-resistant pathogens is making this approach as not more effective, leading to the only solution of device removal and causing devastating consequences for patients. Accordingly, there is a large research about alternative strategies based on the employment of materials holding intrinsic antibacterial properties in order to prevent infections. Between these new strategies, new technologies involving the use of carbon-based materials such as carbon nanotubes, fullerene, graphene and diamond-like carbon shown very promising results. In particular, graphene- and graphene-derived materials (GMs) demonstrated a broad range antibacterial activity toward bacteria, fungi and viruses. These antibacterial activities are attributed mainly to the direct physicochemical interaction between GMs and bacteria that cause a deadly deterioration of cellular components, principally proteins, lipids, and nucleic acids. In fact, GMs hold a high affinity to the membrane proteoglycans where they accumulate leading to membrane damages; similarly, after internalization they can interact with bacteria RNA/DNA hydrogen groups interrupting the replicative stage. Moreover, GMs can indirectly determine bacterial death by activating the inflammatory cascade due to active species generation after entering in the physiological environment. On the opposite, despite these bacteria-targeted activities, GMs have been successfully employed as pro-regenerative materials to favor tissue healing for different tissue engineering purposes. Taken into account these GMs biological properties, this review aims at explaining the antibacterial mechanisms underlying graphene as a promising material applicable in biomedical devices., (Copyright © 2020 Mohammed, Kumar, Bekyarova, Al-Hadeethi, Zhang, Chen, Ansari, Cochis and Rimondini.)

Soft tissue adhesion and infection prevention are currently challenging for dental transmucosal or percutaneous orthopedic implants. It has previously been shown that aligned micro-grooves obtained by Electron Beam (EB) can drive fibroblast alignment for improved soft tissue adhesion. In this work, evidence is presented that the same technique can also be effective for a reduction of the infection risk. Grooves 10-30 µm wide and around 0.2 µm deep were obtained on Ti6Al4V by EB. EB treatment changes the crystalline structure and microstructure in a surface layer that is thicker than the groove depth. Unexpectedly, a significant bacterial reduction was observed. The surfaces were characterized by field emission scanning electron microscopy, X-ray diffraction, confocal microscopy, contact profilometry, wettability and bacterial adhesion tests. The influence of surface topography, microstructure and crystallography on bacterial adhesion was systematically investigated: it was evidenced that the bacterial reduction after EB surface treatment is not correlated with the grooves, but with the microstructure induced by the EB treatment, with a significant bacterial reduction when the surface microstructure has a high density of grain boundaries. This correlation between microstructure and bacterial adhesion was reported for the first time for Ti alloys.

Nowadays, there is a large amount of research aimed at improving the multifunctional behavior of the biomaterials for bone contact, including the concomitant ability to induce apatite formation (bioactivity), fast and effective osteoblasts colonization, and antibacterial activity. The aim of this study is to develop antibacterial and bioactive surfaces (Ti6Al4V alloy and a silica-based bioactive glass) by chemical doping with strontium and/or silver ions. The surfaces were characterized by Scanning Electron Microscopy equipped with Energy Dispersive X ray Spectroscopy (SEM-EDS), X-ray photoelectron spectroscopy (XPS), and Transmission Electron Microscopy (TEM). To better focus on the cells-bacteria competition for the implant surface, in addition to the standard assays for the evaluation of the bacteria adhesion (ISO22196) and for single-cell cultures or biofilm formation, an innovative set of co-cultures of cells and bacteria is here proposed to simulate a competitive surface colonization. The results suggest that all the bioactive tested materials were cytocompatible toward the bone progenitor cells representative for the self-healing process, and that the doped ones were effective in reducing the surface colonization from a pathogenic drug-resistant strain of Staphylococcus aureus . The co-cultures experiments demonstrated that the doped surfaces were able to protect the adhered osteoblasts from the bacteria colonization as well as prevent the infection prior to the surface colonization by the osteoblasts., Competing Interests: The authors declare no conflict of interest.

This work contains original data supporting our research paper "Advances in cartilage repair: the influence of inorganic clays to improve mechanical and healing properties of antibacterial Gellan gum-Manuka honey hydrogels", by Maria A. Bonifacio, Andrea Cochis, Stefania Cometa, Annachiara Scalzone, Piergiorgio Gentile, Giuseppe Procino, Serena Milano, Alessandro C. Scalia, Lia Rimondini, Elvira De Giglio [1]. The main paper describes how four different clays (i.e., mesoporous silica, bentonite and halloysite nanotubes, coded as MS, BE and HNT) as cheap, abundant and versatile feed materials can be used for the preparation of highly performant hydrogels as cartilage substitutes, based on Gellan Gum (GG) and Manuka Honey (MH). Here the composites were further examined by means of Thermogravimetric Analysis (TGA), histological analysis (Alcian blue and Safranin-O) and static compression tests. This set of data strengthens the evidence that these hydrogels possess biological and physicochemical characteristics suitable for their application as reinforcing inorganic fillers in composite materials designed for cartilage regeneration., (© 2019 Published by Elsevier Inc.)

The study explores antibacterial, antiinflammatory and cytoprotective capacity of Pelargonium sidoides DC root extract (PSRE) and proanthocyanidin fraction from PSRE (PACN) under conditions characteristic for periodontal disease. Following previous finding that PACN exerts stronger suppression of Porphyromonas gingivalis compared to the effect on commensal Streptococcus salivarius , the current work continues antibacterial investigation on Staphylococcus aureus , Staphylococcus epidermidis , Aggregatibacter actinomycetemcomitans and Escherichia coli. PSRE and PACN are also studied for their ability to prevent gingival fibroblast cell death in the presence of bacteria or bacterial lipopolysaccharide (LPS), to block LPS- or LPS + IFNγ-induced release of inflammatory mediators, gene expression and surface antigen presentation. Both PSRE and PACN were more efficient in suppressing Staphylococcus and Aggregatibacter compared to Escherichia , prevented A. actinomycetemcomitans - and LPS-induced death of fibroblasts, decreased LPS-induced release of interleukin-8 and prostaglandin E2 from fibroblasts and IL-6 from leukocytes, blocked expression of IL-1β, iNOS, and surface presentation of CD80 and CD86 in LPS + IFNγ-treated macrophages, and IL-1β and COX-2 expression in LPS-treated leukocytes. None of the investigated substances affected either the level of secretion or expression of TNFα. In conclusion, PSRE, and especially PACN, possess strong antibacterial, antiinflammatory and gingival tissue protecting properties under periodontitis-mimicking conditions and are suggestable candidates for treatment of the disease.

Background: Periodontitis is a disease that leads to serious functional and esthetic dysfunctions. Periodontitis exists in different forms, and its etiology is related to multiple component causes. Two key processes involved in the evolution of this pathology are angiogenesis and inflammatory infiltrate. The aim of this study was to understand if important factors such as smoking, gender, age, plaque, pus, and probing pocket depth could influence the histomorphological pattern of generalized stage III-IV, grade C periodontitis (GPIII-IVC), which is a particular form of periodontitis., Methods: Eighteen subjects with GPIII-IVC were enrolled in this study. The percentage of inflammatory cells and the vascular area were measured and evaluated in relation to each periodontal disease-associated factor., Results: Females showed a significant increase in the percentage of inflammatory cells compared to males (6.29% vs. 2.28%, p -value = 0.020) and it was higher in non-smokers than in smokers (4.56% vs. 3.14%, p -value = 0.048). Young patients showed a significant increase in vascular area percentage compared to older patients (0.60% vs. 0.46%, p -value = 0.0006) and this percentage was also higher in non-smokers compared to smokers (0.41% vs. 0.55%, p -value = 0.0008). The vascular area was also more than halved in subjects with residual plaque on tooth surfaces (0.74% vs. 0.36%, p -value = 0.0005)., Conclusions: These results suggested that even if these factors are commonly related to the worsening of periodontal status, some of them (pus and periodontal probing depth (PPD)) do not affect the inflammatory and vascular patterns.

It is widely recognized that surface nanotextures applied on a biomaterial can affect wettability, protein absorption and cellular and/or bacterial adhesion; accordingly, they are nowadays of great interest to promote fast osseointegration and to maintain physiological healing around biomedical implants. In order to be suitable for clinical applications, surface nanotextures must be not only safe and effective, but also, they should be produced through industrial processes scalable to real devices with sustainable processes and costs: this is often a barrier to the market entry. Based on these premises, a chemical surface treatment designed for titanium and its alloys able to produce an oxide layer with a peculiar sponge like nanotexture coupled with high density of hydroxyl group is here presented. The modified Ti-based surfaces previously showed inorganic bioactivity intended as the ability to induce apatite precipitation in simulated body fluid. Physicochemical properties and morphology of the obtained layers have been characterized by means of FESEM, XPS, and Zeta-potential. Biological response to osteoblasts progenitors and bacteria has been tested. The here proposed nanotextured surfaces successfully supported osteoblasts progenitors' adhesion, proliferation and extracellular matrix deposition thus demonstrating good biocompatibility. Moreover, the nanotexture was able to significantly reduce bacteria surface colonization when the orthopedic and the periodontal pathogens Staphylococcus aureus and Aggregatibacter actinomycetemcomitans strains were applied for a short time. Finally, the applicability of the proposed surface treatment to real biomedical devices (a 3D acetabular cup, a dental screw and a micro-sphered laryngeal implant) has been here demonstrated.

The human body is naturally colonized by a huge number of different commensal microbial species, in a relatively stable equilibrium. When this microbial community undergoes dysbiosis at any part of the body, it interacts with the innate immune system and results in a poor health status, locally or systemically. Research studies show that bacteria are capable of significantly influencing specific cells of the immune system, resulting in many diseases, including a neoplastic response. Amongst the multiple different types of diseases, pancreatic cancer and liver cirrhosis were significantly considered in this paper, as they are major fatal diseases. Recently, these two diseases were shown to be associated with increased or decreased numbers of certain oral bacterial species. These findings open the way for a broader perception and more specific investigative studies, to better understand the possible future treatment and prevention. This review aims to describe the correlation between oral dysbiosis and both pancreatic cancer and liver cirrhotic diseases, as well as demonstrating the possible diagnostic and treatment modalities, relying on the oral microbiota, itself, as prospective, simple, applicable non-invasive approaches to patients, by focusing on the state of the art. PubMed was electronically searched, using the following key words: "oral microbiota" and "pancreatic cancer" (PC), "liver cirrhosis", "systemic involvement", and "inflammatory mediators". Oral dysbiosis is a common problem related to poor oral or systemic health conditions. Oral pathogens can disseminate to distant body organs via the local, oral blood circulation, or pass through the gastrointestinal tract and enter into the systemic circulation. Once oral pathogens reach an organ, they modify the immune response and stimulate the release of the inflammatory mediators, this results in a disease. Recent studies have reported a correlation between oral dysbiosis and the increased risk of pancreatic and liver diseases and provided evidence of the presence of oral pathogens in diseased organs. The profound impact that microbial communities have on human health, provides a wide domain towards precisely investigating and clearly understanding the mechanism of many diseases, including cancer. Oral microbiota is an essential contributor to health status and imbalance in this community was correlated to oral and systemic diseases. The presence of elevated numbers of certain oral bacteria, particularly P. gingivalis , as well as elevated levels of blood serum antibodies, against this bacterial species, was associated with a higher risk of pancreatic cancer and liver cirrhosis incidence. Attempts are increasingly directed towards investigating the composition of oral microbiome as a simple diagnostic approach in multiple diseases, including pancreatic and liver pathosis. Moreover, treatment efforts are concerned in the recruitment of microbiota, for remedial purposes of the aforementioned and other different diseases. Further investigation is required to confirm and clarify the role of oral microbiota in enhancing pancreatic and liver diseases. Improving the treatment modalities requires an exertion of more effort, especially, concerning the microbiome engineering and oral microbiota transplantation.

Objective The aim of this work is to evaluate the diagnostic accuracy of 0.3T sectoral MR imaging, compared with arthroscopy, for meniscal, cruciate ligaments and chondral knee lesions. Materials and Methods We conducted a retrospective study analyzing all the consecutive knees subjected to arthroscopy at our institution between January 2014 and June 2017 and preceded within 3 months by knee MR examination at our institution with 0.3 T equipment. Patients with history of a new trauma in the time interval between MR exam and arthroscopy were excluded from the study. Two independent experienced radiologists evaluated in double blind the MR findings of menisci, cruciate ligaments and articular cartilage. Both radiological findings were independently compared with those of the arthroscopic report considered as gold standard. For each of the examined targets we calculated the following parameters: sensitivity, specificity, accuracy, positive and negative predictive value; interobserver concordance statistically calculated using Cohen's Kappa test. Results 214 knees (95R/119L) of 214 patients (143M/71F) aged from 18 to 72 years (mean 44) were included and analyzed. We found a good diagnostic accuracy of the low field MR in identifying the injuries of the menisci (93%) and the crossed ligaments (96%), but a lower accuracy for the articular cartilage (85%). Sensitivity resulted 90% for menisci, 73% for ligaments and 58% for cartilage. Specificity was 91% for menisci, 97% for ligaments and 92% for cartilage. Inter-observer concordance resulted to be excellent for cruciate ligaments (K of Cohen's test = 0.832), good (K = 0.768) for menisci, modest to moderate for articular cartilage (K from 0.236 to 0.389) with worse concordance for tibial cartilage. Conclusions Low-field MR sectoral device with dedicated joint equipment confirms its diagnostic reliability for the evaluation of meniscal and cruciate ligaments lesions but is weak in evaluating low grade chondral lesions.

This work contains original data supporting our research paper "Antibacterial effectiveness meets improved mechanical properties: Manuka Honey/Gellan Gum composite hydrogels for cartilage repair", Bonifacio et al., in press [1], in which innovative composite hydrogels, based on Gellan Gum/Manuka honey/Halloysite nanotubes were described as biomaterials for cartilage regeneration. Here the composites were further examined by means of Fourier Transform Infrared Spectroscopy, in Attenuated Total Reflectance mode (FT-IR/ATR). Materials devoted to cartilage replacement must possess adequate fluid permeability and lubricating capability, therefore, a deeper investigation on water uptake kinetics of freeze-dried specimens up to 21 days in PBS was carried out. Moreover, since the degradation rate of a biomaterial plays a pivotal role in tissue engineering, weight loss measurements of the prepared hydrogels were performed in simulated synovial fluid, in phosphate buffer solution (PBS) and in lysozyme. Scanning Electron Microscopy images provide insight into the morphology of the freeze-dried samples. Finally, additional information on Staphylococcus aureus and Staphylococcus epidermidis ability to adhere onto the prepared hydrogel composites in short times were obtained, as well as the chondrogenic potential of the composites assessed by SDS-PAGE followed by Coomassie blue gel staining.

Air-polishing with low abrasiveness powders is fast arising as a valid and mini-invasive instrument for the management of biofilm colonizing dental implants. In general, the reported advantage is the efficient removal of plaque with respect to the titanium integrity. In the present study, we evaluated the in situ plaque removal and the preventive efficacy in forestalling further infection of an innovative erythritol/chlorhexidine air-polishing powder and compared it with sodium bicarbonate. Accordingly, two peri-implantitis-linked biofilm formers, strains Staphylococcus aureus and Aggregatibacter actinomycetemcomitans , were selected and used to infect titanium disks before and after the air-polishing treatment to test its ability in biofilm removal and re-colonization inhibition, respectively. Biofilm cell numbers and viability were assayed by colony-forming unit (CFU) count and metabolic-colorimetric (2,3-Bis-(2-Methoxy-4-Nitro-5-Sulfophenyl)-2 H -Tetrazolium-5-Carboxanilide) (XTT) assay. Results demonstrated that air-polishing performed with either sodium bicarbonate or erythritol/chlorhexidine was effective in reducing bacteria biofilm viability and number on pre-infected specimens, thus showing a similar ability in counteracting existing infection in situ; on the other hand, when air-polished pre-treated disks were infected, only erythritol/chlorhexidine powder showed higher post-treatment biofilm re-growth inhibition. Finally, surface analysis via mechanical profilometry failed to show an increase in titanium roughness, regardless of the powder selected, thus excluding any possible surface damage due to the use of either sodium bicarbonate or erythritol/chlorhexidine.