Porcine Small Intestinal Submucosa (SIS) as a Suitable Scaffold for the Creation of a Tissue-Engineered Urinary Conduit: Decellularization,Biomechanical and Biocompatibility Characterization Using New Approaches

Bladder cancer (BC) is among the most common malignancies in the world and a relevant cause of cancer mortality. BC is one of the most frequent causes for bladder removal through radical cystectomy, the gold-standard treatment for localized muscle-invasive and some cases of high-risk, non-muscle-invasive bladder cancer. In order to restore urinary functionality, an autologous intestinal segment has to be used to create a urinary diversion. However, several complications are associated with bowel-tract removal, affecting patients’ quality of life. The present study project aims to develop a bio-engineered material to simplify this surgical procedure, avoiding related surgical complications and improving patients’ quality of life. The main novelty of such a therapeutic approach is the decellularization of a porcine small intestinal submucosa (SIS) conduit to replace the autologous intestinal segment currently used as urinary diversion after radical cystectomy, while avoiding an immune rejection. Here, we performed a preliminary evaluation of this acellular product by developing a novel decellularization process based on an environmentally friendly, mild detergent, i.e., Tergitol, to replace the recently declared toxic Triton X-100. Treatment efficacy was evaluated through histology, DNA, hydroxyproline and elastin quantification, mechanical and insufflation tests, two-photon microscopy, FTIR analysis, and cytocompatibility tests. The optimized decellularization protocol is effective in removing cells, including DNA content, from the porcine SIS, while preserving the integrity of the extracellular matrix despite an increase in stiffness. An effective sterilization protocol was found, and cytocompatibility of treated SIS was demonstrated from day 1 to day 7, during which human fibroblasts were able to increase in number and strongly organize along tissue fibres. Taken together, this in vitro study suggests that SIS is a suitable candidate for use in urinary diversions in place of autologous intestinal segments, considering the optimal results of decellularization and cell proliferation. Further efforts should be undertaken in order to improve SIS conduit patency and impermeability to realize a future viable substitute.     

A Modular Composite Device of Poly(Ethylene Oxide)/Poly(Butylene Terephthalate) (PEOT/PBT) Nanofibers and Gelatin as a Dual Drug Delivery System for Local Therapy of Soft Tissue Tumors

In the clinical management of solid tumors, the possibility to successfully couple the regeneration of injured tissues with the elimination of residual tumor cells left after surgery could open doors to new therapeutic strategies. In this work, we present a composite hydrogel–electrospun nanofiber scaffold, showing a modular architecture for the delivery of two pharmaceutics with distinct release profiles, that is potentially suitable for local therapy and post-surgical treatment of solid soft tumors. The composite was obtained by coupling gelatin hydrogels to poly(ethylene oxide)/poly(butylene terephthalate) block copolymer nanofibers. Results of the scaffolds’ characterization, together with the analysis of gelatin and drug release kinetics, displayed the possibility to modulate the device architecture to control the release kinetics of the drugs, also providing evidence of their activity. In vitro analyses were also performed using a human epithelioid sarcoma cell line. Furthermore, publicly available expression datasets were interrogated. Confocal imaging showcased the nontoxicity of these devices in vitro. ELISA assays confirmed a modulation of IL-10 inflammation-related cytokine supporting the role of this device in tissue repair. In silico analysis confirmed the role of IL-10 in solid tumors including 262 patients affected by sarcoma as a negative prognostic marker for overall survival. In conclusion, the developed modular composite device may provide a key-enabling technology for the treatment of soft tissue sarcoma.     

Coded transmissions for space links affected by solar scintillation: Baseband analysis

A thorough analysis of the behavior of error‐correcting codes over space links affected by solar scintillation is presented. The relevant channel parameters are fixed through the development of a model based on real missions' data. Both telecommand and telemetry links are considered in fast and slow fading conditions. Besides classical coherent modulation schemes, the possibility to use noncoherent modulation schemes is considered, to eliminate the problem of phase tracking. For the case of channels with very slow fading, the use of external interleavers or erasure coding is proposed to cope with error bursts.     

Metabolic Syndrome and Male Fertility: Beyond Heart Consequences of a Complex Cardiometabolic Endocrinopathy

Metabolic syndrome (MetS) is a highly prevalent condition among adult males, affecting up to 41% of men in Europe. It is characterized by the association of obesity, hypertension, and atherogenic dyslipidemia, which lead to premature morbidity and mortality due to cardiovascular disease (CVD). Male infertility is another common condition which accounts for about 50% of cases of couple infertility worldwide. Interestingly, male infertility and MetS shares several risk factors (e.g., smoking, ageing, physical inactivity, and excessive alcohol consumption), leading to reactive oxygen species (ROS) production and increased oxidative stress (OS), and resulting in endothelial dysfunction and altered semen quality. Thus, the present narrative review aims to discuss the pathophysiological mechanisms which link male infertility and MetS and to investigate the latest available evidence on the reproductive consequences of MetS.     

Tumor-Stroma Ratio and Programmed Cell Death Ligand 1 Expression in Preoperative Biopsy and Matched Laryngeal Carcinoma Surgical Specimen

Programmed cell death ligand 1 (PD-L1) seems to rely on close relations between neoplastic and immune cells in the tumor microenvironment. Tumor to stroma ratio (TSR) has been associated with prognosis in different malignancies. The aims of this exploratory investigation were to analyze for the first time the: (i) association between TSR, PD-L1 expression and other clinical–pathological features in laryngeal squamous cell carcinoma (LSCC) biopsies and paired surgical specimens; (ii) prognostic and predictive role of TSR and PD-L1. TSR, PD-L1 expression (in terms of combined positive score [CPS]), and other clinical–pathological features were analyzed in biopsies and surgical specimens of 43 consecutive LSCC cases. A CPS < 1 evaluated on surgical specimens was associated with a low TSR (stroma rich) on both biopsies and surgical specimens (p = 0.0143 and p = 0.0063). Low TSR showed a significant negative prognostic value when evaluated on both biopsies and surgical specimens (HR = 8.808, p = 0.0003 and HR = 11.207, p = 0.0002). CPS ≥ 1 appeared to be a favorable prognostic factor (HR = 0.100, p = 0.0265). The association between bioptic and surgical specimen TSR and PD-L1 expression should be further investigated for a potential impact on targeted treatments, also with regard to immunotherapeutic protocols.     

Sol–Gel Synthesis of λ–Na2O·xAl2O3 Films

Na₂O· x Al₂O₃ ( x = 9, 11)films have been obtained by sol–gel method. Crystallization processes during heat treatments have been investigated by X–ray diffraction analysis. A metastable phase with the mullite structure, λ–Na₂O· x Al₂O₃, has been observed starting from 800°C. Films remained stable after a heat treatment at 1000°C for 250 h. Impedance spectroscopy measurements showed that the films of λ-Na₂O· x Al₂O₃ possess a large three–dimensional ionic conductivity at 400°C.     

Nanostructured Silicon Oxide–Nickel Oxide Sol–Gel Films with Enhanced Optical Carbon Monoxide Gas Sensitivity

Sol–gel derived silica (SiO₂) films doped with nickel oxide (NiO) nanocrystals were fabricated. A bifunctional ligand was used, bearing amine groups capable of coordinating the nickel ions and hydrolysable siloxane groups for anchoring the metal complex moiety to the silicate matrix. Nickel oxide nanocrystals precipitated at 500°C while the film was still porous. The nanocomposite films showed a reversible change in the optical transmittance in the VIS-NIR range when exposed to carbon monoxide gas. The effects of residual porosity, testing temperature, and carbon monoxide gas concentration on optical transmittance were studied.     

The binding mode of progesterone to its receptor deduced from molecular dynamics simulations

An unambiguous understanding of the binding mode of human progesterone to its receptor still eludes experimental search. According to the X-ray structure of the ligand-binding domain, only one (O3) of the two keto groups at the ligand ends (O3 and O20) should play a role. This result is in conflict with chemical intuition and the results of site-directed mutagenesis experiments. Herein, we report classical molecular dynamics simulations that reveal the dynamic nature of the binding in solution, elucidate the reasons why X-ray studies failed to determine the role of O20, and clarify the effects of the mutations. The predictive power of the force field is ensured by the consistent introduction of a first-principles representation of the ligand.     

1H nuclear magnetic resonance study of polyurethane prepolymers from toluene diisocyanate and polypropylene glycol

Polyurethane prepolymers prepared from toluene 2,4‐diisocyanate, toluene 2,6‐diisocyanate, and polypropylene glycol with a ratio between the isocyanate and hydroxyl groups equal to 2 were analyzed by ¹H nuclear magnetic resonance (NMR) spectroscopy in acetone‐d₆. Different temperatures and concentrations were used. Toluene 2,4‐dimethylurethane and toluene 2,6‐dimethylurethane were synthesized and used as model compounds to assign prepolymers signals. Measurements of spin–lattice relaxation time T₁ by “inversion recovery” experiments were carried out on toluene 2,4‐diisocyanate, toluene 2,6‐diisocyanate, toluene 2,4‐dimethylurethane, toluene 2,6‐dimethylurethane, and polyurethane prepolymers. Differences in T₁ times were used to interpret prepolymers spectra, by means of the strong observed effect on protons due to the presence of adjacent isocyanate groups. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 87: 347–357, 2003     

An overview of poly(vinyl alcohol) and poly(vinyl pyrrolidone) in pharmaceutical additive manufacturing

Recently, drug personalization has received noticeable attention. Problems arising from standard generalized drug treatments have aroused over the years, particularly among pediatric and geriatric patients. The growing awareness of the limitations of the “one-size-fits-all” approach has progressively led to a rethinking of the current medicine's development, laying the basis of personalized medicine. Three-dimensional printing is a promising tool for realizing personalized therapeutic solutions fitting specific patient needs. This technology offers the possibility to manufacture drug delivery devices with tailored doses, sizes, and release characteristics. Among additive manufacturing techniques, fused deposition modeling (FDM) is the most studied for oral drug delivery device production due to its high precision and cheapness. By playing with factors such as drug loading method, filament production, and printing parameters, the medication release profile of a drug delivery device produced by 3D printing can be tailored depending on the patient's requirements. This review focuses on the applications of FDM in drug fabrication using poly(vinyl alcohol) (PVA) and poly(vinyl pyrrolidone) (PVP) as drug-loaded matrices. The authors aim to provide an overview of the current trends in this research field, with special attention to the effect of the printing parameters, tablet shape, and drug distribution and concentration on drug customization and personalized drug release.