Nanoindentation Response of Structural Self-Healing Epoxy Resin: A Hybrid Experimental-Simulation Approach.

In recent years, self-healing polymers have emerged as a topic of considerable interest owing to their capability to partially restore material properties and thereby extend the product's lifespan. The main purpose of this study is to investigate the nanoindentation response in terms of hardness, reduced modulus, contact depth, and coefficient of friction of a self-healing resin developed for use in aeronautical and aerospace contexts. To achieve this, the bifunctional epoxy precursor underwent tailored functionalization to improve its toughness, facilitating effective compatibilization with a rubber phase dispersed within the host epoxy resin. This approach aimed to highlight the significant impact of the quantity and distribution of rubber domains within the resin on enhancing its mechanical properties. The main results are that pure resin (EP sample) exhibits a higher hardness (about 36.7% more) and reduced modulus (about 7% more), consequently leading to a lower contact depth and coefficient of friction (11.4% less) compared to other formulations that, conversely, are well-suited for preserving damage from mechanical stresses due to their capabilities in absorbing mechanical energy. Furthermore, finite element method (FEM) simulations of the nanoindentation process were conducted. The numerical results were meticulously compared with experimental data, demonstrating good agreement. The simulation study confirms that the EP sample with higher hardness and reduced modulus shows less penetration depth under the same applied load with respect to the other analyzed samples. Values of 877 nm (close to the experimental result of 876.1 nm) and 1010 nm (close to the experimental result of 1008.8 nm) were calculated for EP and the toughened self-healing sample (EP-R-160-T), respectively. The numerical results of the hardness provide a value of 0.42 GPa and 0.32 GPa for EP and EP-R-160-T, respectively, which match the experimental data of 0.41 GPa and 0.30 GPa. This validation of the FEM model underscores its efficacy in predicting the mechanical behavior of nanocomposite materials under nanoindentation. The proposed investigation aims to contribute knowledge and optimization tips about self-healing resins.

Verification of the Self-Healing Ability of PP-co-HUPy Copolymers in Epoxy Systems.

This work concerns the verification of the self-healing ability of PP-co-HUPy copolymers dispersed in epoxy systems. PP is the acronym for the Poly-PEGMA polymer, and HUPy refers to the HEMA-UPy copolymers based on ureidopyrimidinone (UPy) moieties. In particular, this work aims to verify whether this elastomer characterized by an intrinsic self-healing ability can activate supramolecular interactions among polymer chains of an epoxy resin, as in the elastomer alone. The elastomer includes a class of polyethylene glycol monomethyl ether methacrylate-based copolymers, with different percentages of urea-N-2-amino-4-hydroxy-6-methyl pyrimidine-N'-(hexamethylene-n-carboxyethyl methacrylate) (HEMA-UPy) co-monomers. The self-healing capability of these copolymers based on possible quadruple hydrogen bond interactions between polymer chains has been verified. The formulated epoxy samples did not show self-healing efficiency. This can be attributed to the formation of phase segregation that originates during the curing process of the samples, although the PP-co-HUPy copolymers are completely soluble in the liquid epoxy matrix EP. The morphological investigation highlighted the presence of crystals of PP-co-HUPy copolymers, which are in greater quantity in the sample containing the highest weight percentage (7.8 wt%) of HUPy units. Furthermore, the crystals act as promotors for increasing the curing degree (DC) of the epoxy systems containing HUPy units. DC goes from 91.6% for EP to 96.1% and 95.4% for the samples containing weight percentages of 2.5 and 7.8 wt% of HUPy units, respectively. Dynamic mechanical analysis (DMA) shows storage modulus values for epoxy systems containing PP-co-HUPy units lower than that of the unfilled resin EP. The values of maximum in Tan δ (Tg), representing the temperature at which the glass transition occurs, are 220 for the unfilled resin EP, 228 for the sample containing 2.5 wt% of HEMA-UPy units, and 211 for the sample containing 7.8 wt% of HEMA-UPy units.

Contribution of peripheral blood mononuclear cells isolated by advanced filtration system to myogenesis of human bone marrow mesenchymal stem cells co-cultured with myoblasts.

Background: Contribution of peripheral blood mononuclear cells (PBMCs) in myogenesis is still under debate, even though blood filtration systems are commonly used in clinical practice for successfully management of critic limb ischemia. Objectives: A commercial blood filter used for autologous human PBMC transplantation procedures is characterized and used to collect PBMCs, that are then added to well-established 2D in vitro myogenic models assembled with a co-culture of human bone marrow-derived mesenchymal stem cells (hBM-MSCs) and skeletal myoblasts (hSkMs) whit the aim of investigating their potential contribution to stem cell myogenic commitment. Methods: A commercial blood filter was physically and chemically studied to understand its morphological characteristics and composition. PBMCs were concentrated using this system, further isolated by Ficoll-Paque density gradient centrifugation, and then added in an upper transwell chamber to a 2D co-culture of hBM-MSCs and hSkMs. Myogenic commitment was investigated by RT-PCR, immunofluorescence, and flow cytometry immunophenotyping. Cytokine levels were monitored by ELISA assay in culture media. Results: The blood filtration system was disassembled and appeared to be formed by twelve membranes of poly-butylene terephthalate fibers (diameters, 0.9-4.0 µm) with pore size distribution of 1-20 µm. Filter functional characterization was achieved by characterizing collected cells by flow cytometry. Subsequently, collected PBMCs fraction was added to an in-vitro model of hBM-MSC myogenic commitment. In the presence of PBMCs, stem cells significantly upregulated myogenic genes, such as Desmin and MYH2, as confirmed by qRT-PCR and expressed related proteins by immunofluorescence (IF) assay, while downregulated pro-inflammatory cytokines (IL12A at day 14) along the 21 days of culture. Novelty: Our work highlights chemical-physical properties of commercial blood filter and suggests that blood filtrated fraction of PBMC might modulate cytokine expression in response to muscle injury and promote myogenic events, supporting their clinical use in autologous transplantation.

Activity and Selectivity of Novel Chemical Metallic Complexes with Potential Anticancer Effects on Melanoma Cells.

Human malignant melanoma cells from lymph node metastatic site (MeWo) were selected for testing several synthesized and purified silver(I) and gold(I) complexes stabilized by unsymmetrically substituted N-heterocyclic carbene (NHC) ligands, called L20 (N-methyl, N'-[2-hydroxy ethylphenyl]imidazol-2-ylide) and M1 (4,5-dichloro, N-methyl, N'-[2-hydroxy ethylphenyl]imidazol-2-ylide), having halogenide (Cl- or I-) or aminoacyl (Gly=N-(tert-Butoxycarbonyl)glycinate or Phe=(S)-N-(tert-Butoxycarbonyl)phenylalaninate) counterion. For AgL20, AuL20, AgM1 and AuM1, the Half-Maximal Inhibitory Concentration (IC50) values were measured, and all complexes seemed to reduce cell viability more effectively than Cisplatin, selected as control. The complex named AuM1 was the most active just after 8 h of treatment at 5 µM, identified as effective growth inhibition concentration. AuM1 also showed a linear dose and time-dependent effect. Moreover, AuM1 and AgM1 modified the phosphorylation levels of proteins associated with DNA lesions (H2AX) and cell cycle progression (ERK). Further screening of complex aminoacyl derivatives indicated that the most powerful were those indicated with the acronyms: GlyAg, PheAg, AgL20Gly, AgM1Gly, AuM1Gly, AgL20Phe, AgM1Phe, AuM1Phe. Indeed, the presence of Boc-Glycine (Gly) and Boc-L-Phenylalanine (Phe) showed an improved efficacy of Ag main complexes, as well as that of AuM1 derivatives. Selectivity was further checked on a non-cancerous cell line, a spontaneously transformed aneuploid immortal keratinocyte from adult human skin (HaCaT). In such a case, AuM1 and PheAg complexes resulted as the most selective allowing HaCaT viability at 70 and 40%, respectively, after 48 h of treatment at 5 µM. The same complexes tested on 3D MeWo static culture induced partial spheroid disaggregation after 24 h of culture, with almost half of the cells dead.

Multifunctional Properties of Polyhedral Oligomeric Silsesquioxanes (POSS)-Based Epoxy Nanocomposites.

In this study, a tetrafunctional epoxy resin was loaded with 5 wt% of three different types of polyhedral oligomeric silsesquioxane (POSS) compounds, namely, DodecaPhenyl POSS (DPHPOSS), Epoxycyclohexyl POSS (ECPOSS), Glycidyl POSS (GPOSS), and 0.5 wt% of multi-walled carbon nanotubes (CNTs) in order to formulate multifunctional structural nanocomposites tailored for aeronautic and aerospace applications. This work aims to demonstrate how the skillful combination of desired properties, such as good electrical, flame-retardant, mechanical, and thermal properties, is obtainable thanks to the advantages connected with nanoscale incorporations of nanosized CNTs with POSS. The special hydrogen bonding-based intermolecular interactions between the nanofillers have proved to be strategic in imparting multifunctionality to the nanohybrids. All multifunctional formulations are characterized by a Tg centered at values close to 260 °C, fully satisfying structural requirements. Infrared spectroscopy and thermal analysis confirm the presence of a cross-linked structure characterized by a high curing degree of up to 94% and high thermal stability. Tunneling atomic force microscopy (TUNA) allows to detect the map of the electrical pathways at the nanoscale of the multifunctional samples, highlighting a good dispersion of the carbon nanotubes within the epoxy resin. The combined action of POSS with CNTs has allowed to obtain the highest values of self-healing efficiency if compared to those measured for samples containing only POSS in the absence of CNTs.

Nanometric Mechanical Behavior of Electrospun Membranes Loaded with Magnetic Nanoparticles.

This work analyzes on nanoscale spatial domains the mechanical features of electrospun membranes of Polycaprolactone (PCL) loaded with Functionalized Magnetite Nanoparticles (FMNs) produced via an electrospinning process. Thermal and structural analyses demonstrate that FMNs affect the PCL crystallinity and its melting temperature. HarmoniX-Atomic Force Microscopy (H-AFM), a modality suitable to map the elastic modulus on nanometric domains of the sample surface, evidences that the FMNs affect the local mechanical properties of the membranes. The mechanical modulus increases when the tip reveals the magnetite nanoparticles. That allows accurate mapping of the FMNs distribution along the nanofibers mat through the analysis of a mechanical parameter. Local mechanical modulus values are also affected by the crystallinity degree of PCL influenced by the filler content. The crystallinity increases for a low filler percentage (<5 wt.%), while, higher magnetite amounts tend to hinder the crystallization of the polymer, which manifests a lower crystallinity. H-AFM analysis confirms this trend, showing that the distribution of local mechanical values is a function of the filler amount and crystallinity of the fibers hosting the filler. The bulk mechanical properties of the membranes, evaluated through tensile tests, are strictly related to the nanometric features of the complex nanocomposite system.

Correction: Gorrasi et al. Fabrication and Characterization of Electrospun Membranes Based on "Poly(ε-caprolactone)", "Poly(3-hydroxybutyrate)" and Their Blend for Tunable Drug Delivery of Curcumin. Polymers 2020, 12, 2239.

In the original publication [...].

Role of MWCNTs Loading in Designing Self-Sensing and Self-Heating Structural Elements.

This work proposes nanocomposites with carbon nanotubes characterized by self-sensing and self-heating properties. Recently, a growing interest in these two properties has been found in many industrial sectors, especially in the aerospace and automotive fields. While the self-sensing function allows diagnosing the presence of micro-damage in the material thanks to the detection of residual resistance, the self-heating function is exploited to properly tune the heating performance in terms of the heating rate and final temperature values. An electrical percolation value of around 0.5% by weight of carbon nanotubes was found by electrical characterization. The AC conductivity of the nanocomposites, in the range of 100 Hz to 1 MHz, evidences that beyond a CNTs amount of 0.5% wt/wt, they are characterized by a purely resistive behavior. The self-sensing analysis displayed a gauge factor value of 4.1. The solid thermal stability up to 300 °C makes the material suitable as a heating element at high temperatures. SEM investigations and temperature maps evidence a good dispersion of the conductive filler in the epoxy matrix and, consequently, good isotropy in heat distribution. As regards the trend of electrical resistance by varying the temperature, the electro-thermal investigation has shown the presence of both Positive Temperature Coefficient (PTC) and Negative Temperature Coefficient (NTC) behaviors with a predominance of NTC as soon as the temperature becomes closer to the glass transition temperature of the epoxy resin.

Bottom-Up Strategy to Forecast the Drug Location and Release Kinetics in Antitumoral Electrospun Drug Delivery Systems.

Electrospun systems are becoming promising devices usable for topical treatments. They are eligible to deliver different therapies, from anti-inflammatory to antitumoral. In the current research, polycaprolactone electrospun membranes loaded with synthetic and commercial antitumoral active substances were produced, underlining how the matrix-filler affinity is a crucial parameter for designing drug delivery devices. Nanofibrous membranes loaded with different percentages of Dacarbazine (the drug of choice for melanoma) and a synthetic derivative of Dacarbazine were produced and compared to membranes loaded with AuM1, a highly active Au-complex with low affinity to the matrix. AFM morphologies showed that the surface profile of nanofibers loaded with affine substances is similar to one of the unloaded systems, thanks to the nature of the matrix-filler interaction. FTIR analyses proved the efficacy of the interaction between the amidic group of the Dacarbazine and the polycaprolactone. In AuM1-loaded membranes, because of the weak matrix-filler interaction, the complex is mainly aggregated in nanometric domains on the nanofiber surface, which manifests a nanometric roughness. Consequently, the release profiles follow a Fickian behavior for the Dacarbazine-based systems, whereas a two-step with a highly prominent burst effect was observed for AuM1 systems. The performed antitumoral tests evidence the high-cytotoxic activity of the electrospun systems against melanoma cell lines, proving that the synthetic substances are more active than the commercial dacarbazine.

A primary small cell neuroendocrine carcinoma (SCNC) of the oral cavity (cheek mucosa): Description of a case report.

BACKGROUND: Small cell neuroendocrine carcinoma (SCNC) of the oral cavity is a poorly differentiated, high-grade and very aggressive tumor with a poor prognosis. CASE DESCRIPTION: A 64-year-old, Caucasian, smoker man consulted for an ulcero-necrotic, exophytic, lesion of the right retromolar trigone. Haed&neck CT scan showed a right tonsillar tumor lesion. The 18F-PET scan confirmed the presence of a right, highly hypermetabolic tonsillar lesion and two homolateral, cervical lymph nodes. Histology and immunohistochemistry were consisted with the diagnosis of a primary SCNC of the oral cavity. As the tumor was locally advanced and unresectable, the patient underwent a definitive radio-chemotherapy with a cisplatin/etoposide combined regimen (4 cycles). The treatment was well tolerated and led to a complete tumor response. CONCLUSION: The particularity of this case relies on the rarity of the oral SCNC, its difficult and challenging diagnosis, and the complexity of its management that is not validated by large clinical trials, data being extrapolated from small cell lung cancer. In our case, the patient presenting a locally advanced tumor was treated by a combined radio-chemiotherapy leading to a complete tumor regression. The patient's follow up is too short to assess the real benefit of this treatment on overall survival.

A fatal primary gastric melanoma treated by a double immunotherapy with ipilimumab/nivolumab: description of a case report.

Background: Primary gastric melanoma (GM) is a very uncommon tumor with a poor prognosis. Until now, only a few cases have been reported in the literature. Case Description: A 70-year-old, Caucasian, ex-smoker man, presented with asthenia, anorexia, and weight loss of 5 kg during the last 2 months. Biological test showed high levels of transaminases and a microcytic, hypochromic anemia. Whole body CT-scan documented a gastric tumor lesion with concomitant loco-regional lymph node and hepatic metastases. Histology was consisted with the diagnosis of a primary GM. A double immunotherapy with nivolumab and ipilimumab was started but, 2 weeks later, the patient presented an acute hepatic failure quickly leading to his death despite a high dose corticotherapy. Conclusions: The particularity of this case relies on the rarity of GM, its difficult diagnosis representing a clinical challenge, and the complexity of its management that is not validated by large clinical trials, data being extrapolated from the treatment protocols routinely used in cutaneous melanoma. In our case, the patient died 2 weeks after the first cycle of a nivolumab/ipilimumab combined treatment for an acute hepatic failure that could be related to a treatment toxicity or a tumor hyperprogression. The patient's survival was very short not allowing any accurate evaluation of the efficacy of this therapy.

Intravesical Gentamicin: An Option for Therapy and Prophylaxis against Recurrent UTIs and Resistant Bacteria in Neurogenic Bladder Patients on Intermittent Catheterization.

This is a retrospective study of our experience with Gentamicin intravesical instillation as therapy and prophylaxis in patients with lower urinary tract infections (UTIs) undergoing clean intermittent catheterization because of a neurogenic bladder. It is an alternative therapy when all other systemic treatments have failed as it is still an off-label prescription.

Electrospun Membranes Designed for Burst Release of New Gold-Complexes Inducing Apoptosis of Melanoma Cells.

Two non-commercial metallic Au-based complexes were tested against one of the most aggressive malignant melanomas of the skin (MeWo cells), through cell viability and time-lapse live-cell imaging system assays. The tests with the complexes were carried out both in the form of free metallic complexes, directly in contact with the MeWo cell line culture, and embedded in fibers of Polycaprolactone (PCL) membranes produced by the electrospinning technique. Membranes functionalized with complexes were prepared to evaluate the efficiency of the membranes against the melanoma cells and therefore their feasibility in the application as an antitumoral patch for topical use. Both series of tests highlighted a very effective antitumoral activity, manifesting a very relevant cell viability inhibition after both 24 h and 48 h. In the case of the AuM1 complex at the concentration of 20 mM, melanoma cells completely died in this short period of time. A mortality of around 70% was detected from the tests performed using the membranes functionalized with AuM1 complex at a very low concentration (3 wt.%), even after 24 h of the contact period. The synthesized complexes also manifest high selectivity with respect to the MeWo cells. The peculiar structural and morphological organization of the nanofibers constituting the membranes allows for a very effective antitumoral activity in the first 3 h of treatment. Experimental points of the release profiles were perfectly fitted with theoretical curves, which easily allow interpretation of the kinetic phenomena occurring in the release of the synthesized complexes in the chosen medium.

Electromagnetically Stimuli-Responsive Nanoparticles-Based Systems for Biomedical Applications: Recent Advances and Future Perspectives.

Nanoparticles (NPs) in the biomedical field are known for many decades as carriers for drugs that are used to overcome biological barriers and reduce drug doses to be administrated. Some types of NPs can interact with external stimuli, such as electromagnetic radiations, promoting interesting effects (e.g., hyperthermia) or even modifying the interactions between electromagnetic field and the biological system (e.g., electroporation). For these reasons, at present these nanomaterial applications are intensively studied, especially for drugs that manifest relevant side effects, for which it is necessary to find alternatives in order to reduce the effective dose. In this review, the main electromagnetic-induced effects are deeply analyzed, with a particular focus on the activation of hyperthermia and electroporation phenomena, showing the enhanced biological performance resulting from an engineered/tailored design of the nanoparticle characteristics. Moreover, the possibility of integrating these nanofillers in polymeric matrices (e.g., electrospun membranes) is described and discussed in light of promising applications resulting from new transdermal drug delivery systems with controllable morphology and release kinetics controlled by a suitable stimulation of the interacting systems (nanofiller and interacting cells).

A 50-Year-Old Man with Fulminant Alpha-Fetoprotein-Producing Gastric Carcinoma and Disseminated Intravascular Coagulation.

BACKGROUND Alpha-fetoprotein-producing gastric carcinoma (AFPGC) is a rare but aggressive cancer with a poor prognosis. Disseminated intravascular coagulation (DIC) is usually associated with several tumors, including gastric cancer, but only a few cases have been reported in patients with AFPGC. This report describes a case of advanced-stage AFPGC associated with DIC in a 50-year-old White man. CASE REPORT A 50-year-old, White, non-smoker man was hospitalized for a recent left hemiparesis associated with anorexia and loss of weigh. Clinically, we had multiple, hard, irregular, subcutaneous nodules, left supraclavicular lymph nodes, and a left, complete hemiparesis. Laboratory tests showed a DIC. A whole-body CT scan documented multiple lymph node, liver, subcutaneous, bone, and muscular metastases, a right femoral venous thrombosis, a left popliteal arterial thrombosis, and splenic and renal infarcts. The patient underwent an excisional biopsy of a subcutaneous lesion. Histology and immunohistochemistry confirmed the diagnosis of a metastasis from a high-grade AFPGC. Before starting any systemic treatment, the patient presented a massive intraventricular brain hemorrhage, quickly leading to his death. CONCLUSIONS We report a case of metastatic AFPGC associated with a DIC and multiple venous and arterial thromboses resulting in a fatal intracerebral hemorrhage. AFPGC is a distinctive and very difficult to diagnose tumor showing aggressive behavior and poor prognosis.

HER2-positive metastatic, parotid salivary duct carcinoma treated with a trastuzumab/pertuzumab-based chemotherapy: A case report.

This case highlights the rare entity, salivary duct carcinoma (SDC), which is difficult to diagnose and manage. It is the first published case of a metastatic, HER2-positive parotid SDC successfully treated by a dual anti-HER2 treatment associated to a chemotherapy.

Fabrication and Characterization of Electrospun Membranes Based on "Poly(ε-caprolactone)", "Poly(3-hydroxybutyrate)" and Their Blend for Tunable Drug Delivery of Curcumin.

Membranes based on poly(ε-caprolactone)/poly(3-hydroxybutyrate) blends (PCL/PHB at 50 wt%) were obtained by electrospinning and curcumin encapsulated at 1 wt% as active agent, as drug delivery systems for biomedical applications. PCL and PHB were also separately electrospinned and loaded with 1 wt% of curcumin. The processing parameters of PHB were drastically different from PCL and the blend PCL/PHB; in fact, the temperature used was 40 °C, and the distance injector-collector was 28 cm. Different conditions were used for PCL: lower temperature (i.e., 25 °C) and shorter distance injector-collector (i.e., 18 cm). The blend was processed in the same conditions of PCL. The fibers obtained with PHB showed diameters in the order of magnitude of micron (i.e., ≈ 3.45 µm), while the PCL mats is composed of fiber of nanometric dimensions (i.e., ≈ 340 nm). PCL/PHB blend allowed to obtain nanometric fibers (i.e., ≈520 nm). Same trend of results was obtained for the fibers' porosity. The morphology, thermal, mechanical and barrier properties (sorption and diffusion) through water vapor were evaluated on all the electrospun fibers, as well as the release behavior of curcumin, and correlated to the processing parameter and the fibers' morphologies.