Magnetic-Oriented Nickel Particles and Nickel-Coated Carbon Nanotubes: An Efficient Tool for Enhancing Thermal Conductivity of PDMS Composites

In this study, PDMS composites are thermally cured with nickel particles and nickel-coated carbon nanotubes as fillers. Both fillers are oriented with the aim to increase the thermal conductivity of the silicone polymer network, due to the formation of a continuous thermal path. Scanning electron microscopy (SEM) gives a picture of the polymer network's morphology, proving the effective alignment of the nickel particles. Rheology and attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) studies confirm the full curing of the silicon network and no influence in the curing kinetics of the type and content of fillers and their orientation. Dynamic mechanical thermal analysis (DMTA) and tensile analysis show instead different thermo-mechanical behavior of the polymer network due to the presence of different fillers, different fillers percentage, and orientation. Finally, the thermal transmittance coefficient (k) is studied by means of hot disk analysis, revealing the increment of almost 200% due to magnetic filler orientation

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

Surface modification of silicate, borosilicate and phosphate bioactive glasses to improve/control protein adsorption: PART I

Bioactive glasses (BGs) are promising for bone tissue regeneration. BG composition can be tailored, according to the application of interest, and/or functionalized with organic molecules/biomolecules to improve their performances. However, despite the wide knowledge concerning BGs, their interaction with proteins, fundamental for controlling the fate of the implant, has not been deeply investigated yet. Controlling or predicting protein adsorption requires a full understanding of the materials surface physico-chemical properties. In this work, four different BGs (S53P4, B25, SCNB, PhGlass) were surface-modified by four different treatments: 72 h-soaking in TRIS, 72 h soaking in simulated body fluid, APTES grafting and quaternized APTES grafting. The surfaces were then characterized both untreated and after each treatment by contact angle, zeta potential analysis, X-ray photoelectron spectroscopy, Fourier Transform InfraRed–Attenuated Total Reflectance spectroscopy and Scanning Electron Microscopy and Energy Dispersive Spectroscopy. Inductively Coupled Plasma – Optical Emission Spectrometry was then performed to investigate the ion leaching. The aim of this study (Part I) is the physico-chemical characterization of BGs as a function of the implemented treatments, aiming to better understand how the superficial properties are successively affecting protein adsorption. Protein adsorption on untreated and treated BGs will be discussed in a following manuscript (Part II)

Advanced characterization of albumin adsorption on a chemically treated surface for osseointegration: An innovative experimental approach

Surface chemistry, charge, wettability, and roughness affect the adsorbed protein layer, influencing biocompatibility and functionality of implants. Material engineering seeks innovative, sensitive, and reliable characterization techniques for study the adsorbed proteins. These techniques must be suitable to be directly used on the surfaces of clinical interest. In this paper, the characterization of surfaces with topography and chemistry developed for osseointegration is performed by innovative surface analysis techniques to investigate the properties of adsorbed bovine serum albumin. Ti6Al4V alloy chemically treated with an oxidative process to obtain peculiar surface features (roughness and surface hydroxylation) was tested and compared with mirror-polished titanium. Albumin forms a continuous layer on both Ti surfaces when adsorbed from near physiological concentrations, as proved by Kelvin force probe microscopy. It was observed that the hydroxylation degree plays a pivotal role in determining the conformation of proteins after adsorption, where it strongly drives protein unfolding, as confirmed by Surface Enhanced Raman scattering, and in influencing the mechanism and chemical stability of protein-surface interactions, which was highlighted by zeta potential titration curves

Bioactive materials: In vitro investigation of different mechanisms of hydroxyapatite precipitation

Abstract Bioactive materials, able to induce hydroxyapatite precipitation in contact with body fluids, are of great interest for their bone bonding capacity. . The aim of this paper is to compare bioactive materials with different surface features to verify the mechanisms of action and the relationship with kinetics and type of precipitated hydroxyapatite over time. Four different surface treatments for Ti/Ti6Al4V alloy and a bioactive glass were selected and a different mechanism of bioactivity is supposed for each of them. Apart from the conventional techniques (FESEM, XPS and EDX), less common characterizations (zeta potential measurements on solid surfaces and FTIR chemical imaging) were applied. The results suggest that the OH groups on the surface have several effects: the total number of the OH groups mainly affects hydrophilicity of surfaces, while the isoelectric points, surface charge and ions attraction mainly depend on OH acidic/basic strength. Kinetics of hydroxyapatite precipitation is faster when it involves a mechanism of ion exchange while it is slower when it is due to electrostatic effects . The electrostatic effect cooperates with ion exchange and it speeds up kinetics of hydroxyapatite precipitation. Different bioactive surfaces are able to differently induce precipitation of type A and B of hydroxyapatite, as well as different degrees of crystallinity and carbonation. Statement of significance The bone is made of a ceramic phase (a specific type of hydroxyapatite), a network of collagen fibers and the biological tissue. A strong bond of an orthopedic or dental implant with the bone is achieved by bioactive materials where precipitation and growth of hydroxyapatite occurs on the implant surface starting from the ions in the physiological fluids. Several bioactive materials are already known and used, but their mechanism of action is not completely known and the type of precipitated hydroxyapatite not fully investigated. In this work, bioactive titanium and bioglass surfaces are compared through conventional and innovative methodologies. Different mechanisms of bioactivity are identified, with different kinetics and the materials are able to induce precipitation of different types of hydroxyapatite, with different degree of crystallinity and carbonation

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

Human T-Cell Responses to Metallic Ion-Doped Bioactive Glasses

Biomaterials are extensively used as replacements for damaged tissue with bioactive glasses standing out as bone substitutes for their intrinsic osteogenic properties. However, biomaterial implantation has the following risks: the development of implant-associated infections and adverse immune responses. Thus, incorporating metallic ions with known antimicrobial properties can prevent infection, but should also modulate the immune response. Therefore, we selected silver, copper and tellurium as doping for bioactive glasses and evaluated the immunophenotype and cytokine profile of human T-cells cultured on top of these discs. Results showed that silver significantly decreased cell viability, copper increased the T helper (Th)-1 cell percentage while decreasing that of Th17, while tellurium did not affect either cell viability or immune response, as evaluated via multiparametric flow cytometry. Multiplex cytokines assay showed that IL-5 levels were decreased in the copper-doped discs, compared with its undoped control, while IL-10 tended to be lower in the doped glass, compared with the control (plastic) while undoped condition showed lower expression of IL-13 and increased MCP-1 and MIP-1 beta secretion. Overall, we hypothesized that the Th1/Th17 shift, and specific cytokine expression indicated that T-cells might cross-activate other cell types, potentially macrophages and eosinophils, in response to the scaffolds

Surface Functionalisation of biomaterials with alkaline phosphatase

Two different glasses, one biocompatible but with a low bioactivity index (G1) and the other with an higher bioactivity index (G2), the ceramic version of the second glass and a titanium alloy (Ti6Al4V) have been functionalizated by anchoring alkaline phosphatase (ALP) on their surfaces. The enzyme has been chosen because it is involved in mineralization processes of hard tissues and is a model for more complex ones. ALP has been grafted on glasses and glass-ceramics surfaces both with and without samples silanization and on metallic surfaces with and without tresyl chloride activation. Samples have been analyzed at each step of the functionalization process in order to verify i