Vacuum Plasma Treatment Device for Enhancing Fibroblast Activity on Machined and Rough Titanium Surfaces.

This study was conducted to compare the effects of an innovative plasma surface treatment device that does not need a gas supply for titanium disks with two different surface topographies: the prototypical machined surface (MAC) and one of the most diffused roughened ones (SL) obtained through grit blasting and acid etching. A total of 200-MAC and 200-SL titanium disks were used. Each group of disks was divided into four sub-groups of 40 samples each that were subjected to five different tests. Among these, 150-MAC and 150-SL were considered the test group, and they were treated with plasma for 15, 30, and 60 s after being removed from the sterile packaging. On the other hand, 50-MAC and 50-SL were considered the control group, and they were only removed from sterile plastic vials. The samples were analyzed to evaluate the capability of the plasma treatment in influencing protein adsorption, cell adhesion, proliferation, and microbial growth on the test group disks when compared to the untreated disks. Protein adsorption was significantly enhanced after 20 min of plasma treatment for 15 and 30 s on the MAC and SL disks. Plasma treatment for 15 and 30 s significantly increased the level of adhesion in both treated samples after 30 min. Furthermore, the MAC samples showed a significant increase in cell adhesion 4 h after plasma treatment for 15 s. The SEM analysis highlighted that, on the treated samples (especially on the MAC disks), the cells with a polygonal and flat shape prevailed, while the fusiform- and globular-shaped cells were rare. The encouraging results obtained further confirm the effectiveness of plasma treatments on cell adhesion and fibroblast activity.

Fracture strength of 3-units fixed partial dentures fabricated with metal-ceramic, graphene doped PMMA and PMMA before and after ageing: An in-vitro study.

OBJECTIVES: To evaluate the fracture strength and linear elongation at break of three-units fixed partial dentures (FPDs) fabricated with traditional and new materials for fixed prosthodontics before and after ageing. METHODS: Sixty models of three-units FPDs were fabricated and cemented onto a Co-Cr model simulating the replacement of a maxillary second premolar. The samples were randomly divided into 3 groups: metal-ceramic (MCR), graphene-doped polymethylmethacrylate (PMMA-GR) and polymethylmethacrylate (PMMA). Half of the samples were directly subjected to fracture test, while the remaining half underwent an ageing process and then a fracture loading test using an electrodynamic testing machine. Fracture load and elongation at break values were taken and statistically analysed. RESULTS: Significant differences were detected between the different materials (p<0.05). All groups showed a reduction of the fracture load and elongation at break values after ageing, but not statistically significant, except for PMMA group (p = 2.012e-19) (p = 3.8e-11). CONCLUSIONS: MCR and PMMA-GR three-units FPDs showed higher fracture strength and lower elongation at break compared to PMMA. MCR and PMMA-GR had higher resistance to ageing processes compared to PMMA. CLINICAL SIGNIFICANCE: PMMA-GR could be considered a material for long-term provisional restorations as its mechanical behaviour and ageing resistance are more like MCR than PMMA.

Efficacy of a Solution Containing 33% Trichloroacetic Acid and Hydrogen Peroxide in Decontaminating Machined vs. Sand-Blasted Acid-Etched Titanium Surfaces.

This in vitro study assessed the efficacy of a solution containing 33% trichloroacetic acid (CCl3COOH; TCA) and hydrogen peroxide (H2O2) in decontaminating machined (MAC) and sand-blasted acid-etched (SBAE) titanium surfaces. A total of 80 titanium disks were prepared (40 MAC and 40 SBAE). Streptococcus sanguinis and Enterococcus faecalis strains were incubated on 36 samples, while the remaining 44 were kept as controls. Roughness analysis and scanning electron microscopy were used to evaluate the surface features before and after TCAH2O2 treatment. The viability of human adipose-derived mesenchymal stem cells (ASCs) after TCAH2O2 decontamination was assessed with a chemiluminescent assay along with cell morphology through fluorescent staining. TCAH2O2 preserved the surface topography of MAC and SBAE specimens. It also effectively eradicated bacteria on both types of specimens without altering the surface roughness (p > 0.05). Also, no significant differences in protein adsorption between the pristine and TCAH2O2-treated surfaces were found (p = 0.71 and p = 0.94). While ASC proliferation remained unchanged on MAC surfaces, a decrease was observed on the decontaminated SBAE specimens at 24 and 48 h (p < 0.05), with no difference at 72 h (p > 0.05). Cell morphology showed no significant changes after 72 h on both surface types even after decontamination. This study suggests TCAH2O2 as a promising decontamination agent for titanium surfaces, with potential implications for peri-implant health and treatment outcomes.

Denosumab and Zoledronic Acid Differently Affect Circulating Immune Subsets: A Possible Role in the Onset of MRONJ.

This work investigated whether the anti-resorptive drugs (ARDs) zoledronic acid (Zol) and denosumab (Dmab) affect differently the levels of circulating immune cell subsets, possibly predicting the risk of developing medication-related ONJ (MRONJ) during the first 18 months of treatment. Blood samples were collected from 10 bone metastatic breast cancer patients receiving cyclin inhibitors at 0, 6, 12, and 18 months from the beginning of Dmab or Zol treatment. Eight breast cancer patients already diagnosed with MRONJ and treated with cyclin inhibitors and ARDs were in the control group. PBMCs were isolated; the trend of circulating immune subsets during the ARD treatment was monitored, and 12 pro-inflammatory cytokines were analyzed in sera using flow cytometry. In Dmab-treated patients, activated T cells were stable or increased, as were the levels of IL-12, TNF-α, GM-CSF, IL-5, and IL-10, sustaining them. In Zol-treated patients, CD8+T cells decreased, and the level of IFN-γ was undetectable. γδT cells were not altered in Dmab-treated patients, while they dramatically decreased in Zol-treated patients. In the MRONJ control group, Zol-ONJ patients showed a reduction in activated T cells and γδT cells compared to Dmab-ONJ patients. Dmab was less immunosuppressive than Zol, not affecting γδT cells and increasing activated T cells.

Pocket closure after repeated subgingival instrumentation: a stress test to the EFP guideline for stage III-IV periodontitis.

OBJECTIVES: To study the effects of one or two repeated subgingival instrumentations (RSI) in achieving the endpoints of therapy (EoT) in open pockets [residual probing pocket depth (PPD) ≥ 6 mm and PPD 4-5 mm with bleeding on probing (BoP)] after steps I-II of therapy. MATERIALS AND METHODS: Twenty-five patients (3,552 total sites; 1,450 open pockets) with stage III-IV periodontitis received steps I-II of periodontal therapy and were re-evaluated after 4-6 weeks (T1). Residual pockets received RSI at T1 and at 3 months (T2). EoT (PPD < 4 or PPD < 6 BoP-) rate at T1, T2 and 6 months (T3) was computed. The number of needed surgeries and treatment costs were calculated. RESULTS: At T1, 67.6% of open pockets achieved EoT. At residual PPD ≥ 6 mm at T1 (n = 172), one and two RSI resulted in 33.1% and 45.9% of EoT at T2 and T3, respectively. At residual PPD 4-5 mm with BoP at T1 (n = 298), one and two RSI resulted in 66.8% and 72.1% of EoT at T2 and T3, respectively. PPD at T1 predicted EoT after RSI in both cases, while tooth type only in residual PPD 4-5 mm BoP + . At T1, mean number of surgeries per patient and associated costs were significantly higher than after one/two RSI. CONCLUSIONS: RSI may achieve EoT in residual PPD 4-5 mm BoP + and PPD ≥ 6 mm in a considerable number of cases. CLINICAL RELEVANCE: These findings may support the administration of one/two cycles of RSI prior to surgical approach. PROTOCOL REGISTRATION: ClinicalTrials.gov identification number: NCT04826926.

Senescent Markers Expressed by Periodontal Ligament-Derived Stem Cells (PDLSCs) Harvested from Patients with Periodontitis Can Be Rejuvenated by RG108.

Periodontal ligament (PDL) has become an elective source of mesenchymal stem cells (PDLSCs) in dentistry. This research aimed to compare healthy PDLSCs (hPDLSCs) and periodontitis PDLSCs (pPDLSCs) to ascertain any possible functional differences owing to their milieux of origin. Cells were tested in terms of colony-forming unit efficiency; multi differentiating capacity; immunophenotype, stemness, and senescent state were studied by flow cytometry, immunofluorescence, and ß-galactosidase staining; gene expression using RT-PCR. Both hPDLSCs and pPDLSCs were comparable in terms of their immunophenotype and multilineage differentiation capabilities, but pPDLSCs showed a senescent phenotype more frequently. Thus, a selective small molecule inhibitor of DNA methyltransferase (DNMT), RG108, known for its effect on senescence, was used to possibly reverse this phenotype. RG108 did not affect the proliferation and apoptosis of PDLSCs, and it showed little effect on hPDLSCs, while a significant reduction of both p16 and p21 was detected along with an increase of SOX2 and OCT4 in pPDLSCs after treatment at 100 µM RG108. Moreover, the subset of PDLSCs co-expressing OCT4 and p21 decreased, and adipogenic potential increased in pPDLSCs after treatment. pPDLSCs displayed a senescent phenotype that could be reversed, opening new perspectives for the treatment of periodontitis.

Influence of Thickness and Thermocycling on Tensile Strength of Two Resin-Based Cements Used for Overdenture Bar-Type Attachments: An In Vitro Study.

PURPOSE: This study aimed to evaluate the tensile strength of five different thicknesses of two resin cements placed between two titanium surfaces, before and after ageing. MATERIALS AND METHODS: One hundred titanium 5 grade models composed of two surfaces simulating a semiprecision attachment for overdenture and its housing in the framework, were used. Samples were cemented using two different resin cements (SoloCem and OT-Cem). Five groups representing five different cement thicknesses (from 50 to 250µm) were created by varying the housing diameter. A half of the sample underwent to a tensile strength test 24h after luting, while the other half after 30000 thermic cycles from 5°C to 55°C. Shapiro-Wilk and ANOVA with post-hoc tests were performed to relate the tensile strength to the variables: cement type, thermal ageing and cement thickness (p <0.05). RESULTS: Statistical differences were found between the cements both at T0 and T1; the mean values of tensile strength of SoloCem were three times higher than those of OT-Cem. The thermic cycles determined a reduction of the tensile force values for both cements; statistical evidence was found only for the SoloCem except for the 100µm thickness group. Significant differences were also found between the cement thicknesses of both cements, with 50µm and 100µm expressed the best tensile strength. Most of the fractures were of cohesive nature. CONCLUSION: SoloCem showed a higher tensile strength than OT-Cem but has been more stressed by the ageing. For each group the cement thickness influenced the tensile strength values with an inverse relationship.

Mechanical and Biological Characterization of PMMA/Al2O3 Composites for Dental Implant Abutments.

The mechanical and biological behaviors of PMMA/Al2O3 composites incorporating 30 wt.%, 40 wt.%, and 50 wt.% of Al2O3 were thoroughly characterized as regards to their possible application in implant-supported prostheses. The Al2O3 particles accounted for an increase in the flexural modulus of PMMA. The highest value was recorded for the composite containing 40 wt.% Al2O3 (4.50 GPa), which was about 18% higher than that of its unfilled counterpart (3.86 GPa). The Al2O3 particles caused a decrease in the flexural strength of the composites, due to the presence of filler aggregates and voids, though it was still satisfactory for the intended application. The roughness (Ra) and water contact angle had the same trend, ranging from 1.94 µm and 77.2° for unfilled PMMA to 2.45 µm and 105.8° for the composite containing the highest alumina loading, respectively, hence influencing both the protein adsorption and cell adhesion. No cytotoxic effects were found, confirming that all the specimens are biocompatible and capable of sustaining cell growth and proliferation, without remarkable differences at 24 and 48 h. Finally, Al2O3 was able to cause strong cell responses (cell orientation), thus guiding the tissue formation in contact with the composite itself and not enhancing its osteoconductive properties, supporting the PMMA composite's usage in the envisaged application.

Bioactive glass for periodontal regeneration: a systematic review.

BACKGROUND: One of the major clinical challenges of this age could be represented by the possibility to obtain a complete regeneration of infrabony defects. Over the past few years, numerous materials and different approaches have been developed to obtain bone and periodontal healing. Among all biomaterials, bioglasses (BG) are one of the most interesting due to their ability to form a highly reactive carbonate hydroxyapatite layer. Our aim was to systematically review the literature on the use and capability of BG for the treatment of periodontal defects and to perform a meta-analysis of their efficacy. METHODS: A search of MEDLINE/PubMed, Cochrane Library, Embase and DOSS was conducted in March 2021 to identify randomized controlled trials (RCTs) using BG in the treatment of intrabony and furcation defects. Two reviewers selected the articles included in the study considering the inclusion criteria. The outcomes of interest were periodontal and bone regeneration in terms of decrease of probing depth (PD) and gain of clinical attachment level (CAL). A network meta-analysis (NMA) was fitted, according to the graph theory methodology, using a random effect model. RESULTS: Through the digital search, 46 citations were identified. After duplicate removal and screening process, 20 articles were included. All RCTs were retrieved and rated following the Risk of bias 2 scale, revealing several potential sources of bias. The meta-analysis focused on the evaluation at 6 months, with 12 eligible articles for PD and 10 for CAL. As regards the PD at 6 months, AUTOGENOUS CORTICAL BONE, BIOGLASS and PLATELET RICH FIBRIN were more efficacious than open flap debridement alone, with a statistically significant standardized mean difference (SMD) equal to -1.57, -1.06 and - 2.89, respectively. As to CAL at 6 months, the effect of BIOGLASS is reduced and no longer significant (SMD = -0.19, p-value = 0.4) and curiously PLATELET RICH FIBRIN was more efficacious than OFD (SMD =-4.13, p-value < 0.001) in CAL gain, but in indirect evidence. CONCLUSIONS: The present review partially supports the clinical efficacy of BG in periodontal regeneration treatments for periodontal purposes. Indeed, the SMD of 0.5 to 1 in PD and CAL obtained with BG compared to OFD alone seem clinically insignificant even if it is statistically significant. Heterogeneity sources related to periodontal surgery are multiple, difficult to assess and likely hamper a quantitative assessment of BG efficacy.

E15.5 Mouse Embryo Micro-CT Using a Bruker Skyscan 1172 Micro-CT.

X-ray computed microtomography (µCT) is a powerful tool to reveal the 3D structure of tissues and organs. Compared with the traditional sectioning, staining, and microscopy image acquisition, it allows a better understanding of the morphology and a precise morphometric analysis. Here, we describe a method for 3D visualization and morphometric analysis by µCT scanning of the embryonic heart of iodine-stained E15.5 mouse embryos.

Immune Dysfunction in Medication-Related Osteonecrosis of the Jaw.

The pathogenesis of medication-related osteonecrosis of the jaw (MRONJ) is multifactorial and there is a substantial consensus on the role of antiresorptive drugs (ARDs), including bisphosphonates (BPs) and denosumab (Dmab), as one of the main determinants. The time exposure, cumulative dose and administration intensity of these drugs are critical parameters to be considered in the treatment of patients, as cancer patients show the highest incidence of MRONJ. BPs and Dmab have distinct mechanisms of action on bone, but they also exert different effects on immune subsets which interact with bone cells, thus contributing to the onset of MRONJ. Here, we summarized the main effects of ARDs on the different immune cell subsets, which consequently affect bone cells, particularly osteoclasts and osteoblasts. Data from animal models and MRONJ patients showed a deep interference of ARDs in modulating immune cells, even though a large part of the literature concerns the effects of BPs and there is a lack of data on Dmab, demonstrating the need to further studies.

The Impact of Plasma Membrane Ion Channels on Bone Remodeling in Response to Mechanical Stress, Oxidative Imbalance, and Acidosis.

The extracellular milieu is a rich source of different stimuli and stressors. Some of them depend on the chemical-physical features of the matrix, while others may come from the 'outer' environment, as in the case of mechanical loading applied on the bones. In addition to these forces, a plethora of chemical signals drives cell physiology and fate, possibly leading to dysfunctions when the homeostasis is disrupted. This variety of stimuli triggers different responses among the tissues: bones represent a particular milieu in which a fragile balance between mechanical and metabolic demands should be tuned and maintained by the concerted activity of cell biomolecules located at the interface between external and internal environments. Plasma membrane ion channels can be viewed as multifunctional protein machines that act as rapid and selective dual-nature hubs, sensors, and transducers. Here we focus on some multisensory ion channels (belonging to Piezo, TRP, ASIC/EnaC, P2XR, Connexin, and Pannexin families) actually or potentially playing a significant role in bone adaptation to three main stressors, mechanical forces, oxidative stress, and acidosis, through their effects on bone cells including mesenchymal stem cells, osteoblasts, osteoclasts, and osteocytes. Ion channel-mediated bone remodeling occurs in physiological processes, aging, and human diseases such as osteoporosis, cancer, and traumatic events.

Bacterial and Cellular Response to Yellow-Shaded Surface Modifications for Dental Implant Abutments.

Dental implants have dramatically changed the rehabilitation procedures in dental prostheses but are hindered by the possible onset of peri-implantitis. This paper aims to assess whether an anodization process applied to clinically used surfaces could enhance the adhesion of fibroblasts and reduce bacterial adhesion using as a reference the untreated machined surface. To this purpose, four different surfaces were prepared: (i) machined (MAC), (ii) machined and anodized (Y-MAC), (iii) anodized after sand-blasting and acid etching treatment (Y-SL), and (iv) anodized after double acid etching (Y-DM). All specimens were characterized by scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDX). Moreover, the mean contact angle in both water and diiodomethane as well as surface free energy calculation was assessed. To evaluate changes in terms of biological responses, we investigated the adhesion of Streptococcus sanguinis (S. sanguinis) and Enterococcus faecalis (E. faecalis), fetal bovine serum (FBS) adsorption, and the early response of fibroblasts in terms of cell adhesion and viability. We found that the anodization reduced bacterial adhesion, while roughened surfaces outperformed the machined ones for protein adsorption, fibroblast adhesion, and viability independently of the treatment. It can be concluded that surface modification techniques such as anodization are valuable options to enhance the performance of dental implants.

Challenges of Periodontal Tissue Engineering: Increasing Biomimicry through 3D Printing and Controlled Dynamic Environment.

In recent years, tissue engineering studies have proposed several approaches to regenerate periodontium based on the use of three-dimensional (3D) tissue scaffolds alone or in association with periodontal ligament stem cells (PDLSCs). The rapid evolution of bioprinting has sped up classic regenerative medicine, making the fabrication of multilayered scaffolds-which are essential in targeting the periodontal ligament (PDL)-conceivable. Physiological mechanical loading is fundamental to generate this complex anatomical structure ex vivo. Indeed, loading induces the correct orientation of the fibers forming the PDL and maintains tissue homeostasis, whereas overloading or a failure to adapt to mechanical load can be at least in part responsible for a wrong tissue regeneration using PDLSCs. This review provides a brief overview of the most recent achievements in periodontal tissue engineering, with a particular focus on the use of PDLSCs, which are the best choice for regenerating PDL as well as alveolar bone and cementum. Different scaffolds associated with various manufacturing methods and data derived from the application of different mechanical loading protocols have been analyzed, demonstrating that periodontal tissue engineering represents a proof of concept with high potential for innovative therapies in the near future.

Plasma of Argon Treatment of the Implant Surface, Systematic Review of In Vitro Studies.

This paper aims to review the evidence of the cellular activity on titanium samples exposed to Plasma of Argon (PoA) treatment. A systematic review was carried out based on the PRISMA statement by searching the Cochrane Library, PubMed, Web of Science, EMBASE and Scopus, up to October 2020. Papers were selected according to PICOS format that is: Population (P): osteoblasts, fibroblasts, gingival cells; Intervention (I): PoA disinfection treatment; Comparison (C): untreated controls; Outcome (O): cell culture; Setting (S): in vitro assays. The quality assessment was performed according to the CRIS Guidelines (Checklist for Reporting In vitro Studies). A total of 661 articles were found, of which 16 were included. The quality assessment revealed an overall poor quality of the studies analyzed. In vitro studies on the potential of PoA showed a potential effect in promoting higher cell adhesion and protein adsorption in the earliest times (hours). This outcome was not so evident when later stages of cell growth on the surfaces were tested and compared to the control groups. Only one study was conducted in vivo on a human sample regarding abutment cleaning. No meta-analysis was conducted because of the variety of experimental settings, mixed methods and different cell lines studied. PoA seems to be effective in promoting cell adhesion and protein adsorption. The duration of this effect remains unclear. Further evidence is required to demonstrate the long-term efficacy of the treatment and to support the use of PoA treatment in clinical practice.

The TFEB-TGIF1 axis regulates EMT in mouse epicardial cells.

Epithelial-mesenchymal transition (EMT) is a complex and pivotal process involved in organogenesis and is related to several pathological processes, including cancer and fibrosis. During heart development, EMT mediates the conversion of epicardial cells into vascular smooth muscle cells and cardiac interstitial fibroblasts. Here, we show that the oncogenic transcription factor EB (TFEB) is a key regulator of EMT in epicardial cells and that its genetic overexpression in mouse epicardium is lethal due to heart defects linked to impaired EMT. TFEB specifically orchestrates the EMT-promoting function of transforming growth factor (TGF) ß, and this effect results from activated transcription of thymine-guanine-interacting factor (TGIF)1, a TGFß/Smad pathway repressor. The Tgif1 promoter is activated by TFEB, and in vitro and in vivo findings demonstrate its increased expression when Tfeb is overexpressed. Furthermore, Tfeb overexpression in vitro prevents TGFß-induced EMT, and this effect is abolished by Tgif1 silencing. Tfeb loss of function, similar to that of Tgif1, sensitizes cells to TGFß, inducing an EMT response to low doses of TGFß. Together, our findings reveal an unexpected function of TFEB in regulating EMT, which might provide insights into injured heart repair and control of cancer progression.

Disinfection and Biocompatibility of Titanium Surfaces Treated with Glycine Powder Airflow and Triple Antibiotic Mixture: An In Vitro Study.

The aim of this in vitro study was to compare three disinfection protocols of biofilm-coated machined (MAC) and acid etched (SLA) commercial pure Grade 4 Titanium disks. Samples were infected with a vial of polymicrobial biofilm to simulate peri-implantitis in vitro. Seventeen MAC and twenty SLA titanium disks were randomly assigned to: (1) glycine powder air-flow (GYPAP) for 1 min; (2) a local delivered triple paste antibiotic composed by a gel mixture with ciprofloxacin, metronidazole, and clarithromycin (3MIX) for 1 h; and (3) a combination of both (GYPAP + 3MIX). Biocompatibility of the titanium disks after each treatment protocol was assessed by measurement of adhesion and growth of adipose-derived mesenchymal stem cells (ASCs) after 24 and 72 h. A confocal laser scanning microscope (CLSM) assessed the antibacterial effect of each treatment. Data of the antibacterial efficacy and cell viability were presented as mean with standard deviation and calculated by one-way ANOVA with multiple comparisons via Bonferroni tests. Results were considered significant with p < 0.05. The higher cell viability was achieved by the 3MIX and GYPAP combination on the SLA surfaces after 72 h. CLSM analysis showed a mean ratio of dead bacteria statistically higher in the 3MIX + GYPAP group compared with the GYPAP and 3MIX subgroups (p < 0.05). In conclusion, data showed that the combination of GYPAP and 3MIX could be preferred to the other protocols, especially in presence of SLA titanium surface.

CD73/Adenosine Pathway Involvement in the Interaction of Non-Small Cell Lung Cancer Stem Cells and Bone Cells in the Pre-Metastatic Niche.

Adenosinergic signaling is an important regulator of tissue homeostasis and extracellular accumulation of adenosine (Ado) and is associated with different pathologies, such as cancer. In non-small-cell lung cancer (NSCLC), a subset of CD133/CXCR4+ cancer stem cell (CSCs) has been demonstrated to initiate bone metastases. Here we investigated how NSCLC CSCs interact with osteoclasts (OCs) and osteoblasts (OBs) by modulating Ado production and OC activity. We proved that CSC-spheres, generated in vitro from NSCLC cell lines, express CD38, PC-1, and CD73, enzymes of the non-canonical adenosinergic pathway, produce high level of Ado, and down-regulate A1R and A3R inhibitory receptors, while expressing A2AR and A2BR. To address the Ado role and modulation of the in-bone pre-metastatic niche, we performed co-cultures of CSC-spheres with OCs and OBs cells. Firstly, we verified that active OCs do not activate non-canonical the adenosinergic pathway, conversely to OBs. OCs co-cultured with CSC-spheres increase Ado production that is related to the OC resorption activity and contributes to T-cell suppression. Finally, we proved the efficacy of anti-CD73 agents in blocking NSCLC cell migration. Overall, we assessed the importance of adenosinergic signaling in the interaction between CSCs and OCs at the pre-metastatic niche, with therapeutic implications related to Ado production.

Endothelial Heme Dynamics Drive Cancer Cell Metabolism by Shaping the Tumor Microenvironment.

The crosstalk among cancer cells (CCs) and stromal cells within the tumor microenvironment (TME) has a prominent role in cancer progression. The significance of endothelial cells (ECs) in this scenario relies on multiple vascular functions. By forming new blood vessels, ECs support tumor growth. In addition to their angiogenic properties, tumor-associated ECs (TECs) establish a unique vascular niche that actively modulates cancer development by shuttling a selected pattern of factors and metabolites to the CC. The profile of secreted metabolites is strictly dependent on the metabolic status of the cell, which is markedly perturbed in TECs. Recent evidence highlights the involvement of heme metabolism in the regulation of energy metabolism in TECs. The present study shows that interfering with endothelial heme metabolism by targeting the cell membrane heme exporter Feline Leukemia Virus subgroup C Receptor 1a (FLVCR1a) in TECs, resulted in enhanced fatty acid oxidation (FAO). Moreover, FAO-derived acetyl-CoA was partly consumed through ketogenesis, resulting in ketone bodies (KBs) accumulation in FLVCR1a-deficient TECs. Finally, the results from this study also demonstrate that TECs-derived KBs can be secreted in the extracellular environment, inducing a metabolic rewiring in the CC. Taken together, these data may contribute to finding new metabolic vulnerabilities for cancer therapy.

Electron-Beam-Induced Grafting of Chitosan onto HDPE/ATZ Composites for Biomedical Applications.

The surface functionalisation of high-density polyethylene (HDPE) and HDPE/alumina-toughened zirconia (ATZ) surfaces with chitosan via electron-beam (EB) irradiation technique was exploited for preparing materials suitable for biomedical purposes. ATR-FTIR analysis and wettability measurements were employed for monitoring the surface changes after both irradiation and chitosan grafting reaction. Interestingly, the presence of ATZ loadings beyond 2 wt% influenced both the EB irradiation process and the chitosan functionalisation reaction, decreasing the oxidation of the surface and the chitosan grafting. The EB irradiation induced an increase in Young's modulus and a decrease in the elongation at the break of all analysed systems, whereas the tensile strength was not affected in a relevant way. Biological assays indicated that electrostatic interactions between the negative charges of the surface of cell membranes and the -NH3+ sites on chitosan chains promoted cell adhesion, while some oxidised species produced during the irradiation process are thought to cause a detrimental effect on the cell viability.