Tribological behaviour of Ti or Ti alloy vs. zirconia in presence of artificial saliva

Abutment is the transmucosal component in a dental implant system and its eventual appearance has a major impact on aesthetics: use of zirconia abutments can be greatly advantageous in avoiding this problem. Both in the case of one and two-piece zirconia abutments, a critical issue is severe wear between the zirconia and titanium components. High friction at this interface can induce loosening of the abutment connection, production of titanium wear debris, and finally, peri-implant gingivitis, gingival discoloration, or marginal bone adsorption can occur. As in vivo wear measurements are highly complex and time-consuming, wear analysis is usually performed in simulators in the presence of artificial saliva. Different commercial products and recipes for artificial saliva are available and the effects of the different mixtures on the tribological behaviour is not widely explored. The specific purpose of this research was to compare two types of artificial saliva as a lubricant in titanium-zirconia contact by using the ball on disc test as a standard tribological test for materials characterisation. Moreover, a new methodology is suggested by using electrokinetic zeta potential titration and contact angle measurements to investigate the chemical stability at the titanium-lubricant interface. This investigation is of relevance both in the case of using zirconia abutments and artificial saliva against chronic dry mouth. Results suggest that an artificial saliva containing organic corrosion inhibitors is able to be firmly mechanically and chemically adsorb on the surface of the Ti c.p. or Ti6Al4V alloy and form a protective film with high wettability. This type of artificial saliva can significantly reduce the friction coefficient and wear of both the titanium and zirconia surfaces. The use of this type of artificial saliva in standard wear tests has to be carefully considered because the wear resistance of the materials can be overestimated while it can be useful in some specific clinical applications. When saliva is free from organic corrosion inhibitors, wear occurs with a galling mechanism. The occurrence of a super-hydrophilic saliva film that is not firmly adsorbed on the surface is not efficient in order to reduce wear. The results give both suggestions about the experimental conditions for lab testing and in vivo performance of components of dental implants when artificial saliva is used

Electron beam structuring of Ti6Al4V: New insights on the metal surface properties influencing the bacterial adhesion

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 \u3bcm wide and around 0.2 \u3bcm 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

Antibody-drug conjugates for lymphoma patients: preclinical and clinical evidences

Antibody-drug conjugates (ADCs) are a recent, revolutionary approach for malignancies treatment, designed to provide superior efficacy and specific targeting of tumor cells, compared to systemic cytotoxic chemotherapy. Their structure combines highly potent anti-cancer drugs (payloads or warheads) and monoclonal antibodies (Abs), specific for a tumor-associated antigen, via a chemical linker. Because the sensitive targeting capabilities of monoclonal Abs allow the direct delivery of cytotoxic payloads to tumor cells, these agents leave healthy cells unharmed, reducing toxicity. Different ADCs have been approved by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of a wide range of malignant conditions, both as monotherapy and in combination with chemotherapy, including for lymphoma patients. Over 100 ADCs are under preclinical and clinical investigation worldwide. This paper provides an overview of approved and promising ADCs in clinical development for the treatment of lymphoma. Each component of the ADC design, their mechanism of action, and the highlights of their clinical development progress are discussed

Recurrence of the oxazole motif in tubulin colchicine site inhibitors with anti-tumor activity

Because of its wide spectrum of targets and biological activities, the oxazole ring is a valuable heterocyclic scaffold in the design of new therapeutic agents with anticancer, antiviral, antibacterial, anti-inflammatory, neuroprotective, antidiabetic and antidepressant properties. The presence of two heteroatoms, oxygen and nitrogen, offers possible interactions (hydrogen, hydrophobic, van der Waals or dipoles bonds) with a broad range of receptors and enzymes. Furthermore, the oxazole core conjugates low cytotoxicity with improved compound solubility and is well suited to structural modifications such as substitution with different groups and condensation to aromatic, heteroaromatic or non-aromatic rings, offering diversity when introduced into scaffolds. These features make it a very attractive nucleus in medicinal chemistry. Herein we present a diverse array of oxazole derivatives with potential therapeutic use in multiple tumor models. The emphasis has been addressed to compounds with anti-tubulin activity reported in literature in the last decade, describing their structural features, efficiency and future perspectives

Surface Properties and Antioxidant Activity of Silicate and Borosilicate Bioactive Glasses

Herein, silicate and borosilicate bioactive glasses are synthetized and characterized. The antioxidant activity, in the presence and absence of human osteoblasts' progenitor cells, of the different glass compositions, is correlated to the surface properties: wettability, zeta potential, hydroxylation degree, reactivity in simulated body fluid (SBF), and Tris buffer. An enhancing effect of boron in glass reactivity and a stabilizing role of Sr and Mg are evidenced. The scavenging potential of the analyzed bioactive glasses toward reactive oxygen species (ROS) is clearly proved. Moreover, cellular tests confirm the protective effect of the bioactive glasses toward viable cells acting as ROS/RNS species scavenger. The obtained results represent an original improvement of the knowledge concerning the intrinsic antioxidant ability of bioactive glasses with different compositions and the mechanisms involved

Coating of bioactive glasses with chitosan: The effects of the glass composition and coating method on the surface properties, including preliminary in vitro results

Two bioactive glasses were coated with chitosan: SCNB belongs to the SiO2-CaO-Na2O system, and SCNA has the addition of Al2O3 to enhance chemical stability. Different coating methods were compared: direct physical attachment, surface activation through tresyl chloride, and polydopamine as a linker. The samples were char-acterized through SEM-EDS, contact angle measurements, FTIR, zeta potential titrations, tape tests, in vitro precipitation of hydroxylapatite (bioactivity), and cell cultures (RAW 264.7 and UMR-106) on some selected samples. Direct physical attachment (in acetic acid) or use of polydopamine allowed complete surface coverage, while it dropped to one-quarter on both glasses by using tresyl chloride. The coating had a contact angle of about 80 degrees and it well showed typical functional groups (FTIR). The coatings on SCNA were chemically and mechan-ically stable (classified as 4-5B by the tape tests, partially maintained after soaking for 14 days), and showed an isoelectric point around 8. On SCNB, the coatings were unstable (classified as 0-3B, dissolved during soaking) but bioactivity was preserved. The coating affected the biological outcome of SCNA with M0/M1 polarization (1 day) and reduced viability of macrophages (3 days), while osteoblastic cells showed poor adhesion but maintained cell viability and osteogenic potential (3-7 days)

Effects of rmBMP-7 on Osteoblastic Cells Grown on a Nanostructured Titanium Surface

This study evaluates the effects of the availability of exogenous BMP-7 on osteoblastic cells’ differentiation on a nanotextured Ti surface obtained by chemical etching (Nano-Ti). The MC3T3-E1 and UMR-106 osteoblastic cell lines were cultured for 5 and 7 days, respectively, on a Nano-Ti surface and on a control surface (Control-Ti) in an osteogenic medium supplemented with either 40 or 200 ng/mL recombinant mouse (rm) BMP-7. The results showed that MC3T3-E1 cells exhibited distinct responsiveness when exposed to each of the two rmBMP-7 concentrations, irrespective of the surface. Even with 40 ng/mL rmBMP-7, important osteogenic effects were noticed for Control-Ti in terms of cell proliferation potential; Runx2, Osx, Alp, Bsp, Opn, and Smad1 mRNA expression; and in situ ALP activity. For Nano-Ti, the effects were limited to higher Alp, Bsp, and Opn mRNA expression and in situ ALP activity. On both surfaces, the osteogenic potential of UMR-106 cultures remained unaltered with 40 ng/mL rmBMP-7, but it was significantly reduced when the cultures were exposed to the 200 ng/mL concentration. The availability of rmBMP-7 to pre-osteoblastic cells at the concentrations used alters the expression profile of osteoblast markers, indicative of the acquisition of a more advanced stage of osteoblastic differentiation. This occurs less pronouncedly on the nanotextured Ti and without reflecting in higher mineralized matrix production by differentiated osteoblasts on both surfaces

Copanlisib synergizes with conventional and targeted agents including venetoclax in B- And T-cell lymphoma models

Copanlisib is a pan-class I phosphoinositide 3-kinase (PI3K) inhibitor with preferred activity toward PI3Ka and PI3Kd. Despite the clear overall clinical benefit, the number of patients achieving complete remissions with the single agent is relatively low, a problem shared by the vast majority of targeted agents. Here, we searched for novel copanlisib-based combinations. Copanlisib was tested as a single agent, in combination with an additional 17 drugs in 26 cell lines derived from mantle cell lymphoma (MCL), marginal zone lymphoma (MZL), and T-cell lymphomas. In vivo experiments, transcriptome analyses, and immunoblotting experiments were also performed. Copanlisib as a single agent showed in vitro dose-dependent antitumor activity in the vast majority of the models. Combination screening identified several compounds that synergized with copanlisib. The strongest combination was with the B-cell lymphoma 2 (BCL2) inhibitor venetoclax. The benefit of the combination over single agents was also validated in an MZL xenograft model and in MCL primary cells, and was due to increased induction of apoptosis, an effect likely sustained by the reduction of the antiapoptotic proteins myeloid cell leukemia 1 (MCL1) and BCL-XL, observed in MCL and MZL cell lines, respectively. These data supported the rationale for the design of the Swiss Group for Clinical Cancer Research (SAKK) 66/18phase 1 study currently exploring the combination of copanlisib and venetoclax in relapsed/refractory lymphomas

Lembo miofasciale di vasto laterale nella ricostruzione della lingua

Nell'ultimo decennio il lembo antero-laterale di coscia (ALT) è diventato il lembo libero più utilizzato nella ricostruzione della lingua, dal momento che esso è caratterizzato da bassa morbidità a livello del sito donatore e da migliori risultati estetici. Tuttavia, l'ALT fascio-cutaneo può essere insufficiente nella ricostruzione nei difetti maggiori (es. glossectomia totale) mentre la sua variante muscolo-cutanea (che include il muscolo vasto laterale)' può essere troppo voluminosa. Scopo dello studio è quello di descrivere la nostra esperienza preliminare nella ricostruzione della lingua utilizzando il lembo libero mio-fasciale di vasto laterale che potrebbe a nostro parere offrire notevoli vantaggi nella ricostruzione testa-collo come: possibilità di confezionare un lembo voluminoso quando necessario, ottimi risultati funzionali, obliterazione di spazi morti con prevenzione dello sviluppo di fistola e infezione con minima morbidità a livello del sito donatore