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In order to limit the ever-increasing consumption of new resources for material formulations, regulations and legislation require us to move from a linear to a circular economy and to find efficient ways to recycle, reuse and recover materials. Taking into account the principles of material circularity and waste reuse, this research study aims to produce thermoplastic composites using two types of industrial waste from neighbouring companies, namely waste polypropylene (wPP) from household production and carbon-fibre-reinforced epoxy composite scrap from a pultrusion company. The industrial scrap of the carbon-fibre-reinforced epoxy composites was either machined/ground to powder (pCFRC) and used directly as a reinforcement agent or subjected to a chemical digestion process to recover the carbon fibres (rCFs). Both pCFRC and rCF, at different weight ratios, were melt-blended with wPP. Prior to melt blending, both pCFRC and rCF were analysed for morphology by scanning electron microscopy (SEM). The pCFRC powder contains epoxy resin fragments with spherical to ellipsoidal shape and carbon fibre fragments. The rCFs are clean from the matrix, but they are slightly thicker and corrugated after the matrix digestion. Further, the morphologies of wPP/pCFRC and wPP/rCF were also investigated by SEM, while the thermal behaviour, i.e., transitions and changes in crystallinity, and thermal resistance were evaluated by differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA), respectively. The strength of the interaction between the filler (i.e., pCFRC or rCF) and the wPP matrix and the processability of these composites were assessed by rheological studies. Finally, the mechanical properties of the systems were characterised by tensile tests, and as found, both pCFRC and rCF exert reinforcement effects, although better results were obtained using rCF. The wPP/pCFRC results are more heterogeneous than those of the wPP/rCF due to the presence of epoxy and carbon fibre fragments, and this heterogeneity could be considered responsible for the mechanical behaviour. Further, the presence of both pCFRC and rCF leads to a restriction of polymer chain mobility, which leads to an overall reduction in ductility. All the results obtained suggest that both pCFRC and rCF are good candidates as reinforcing fillers for wPP and that these complex systems could potentially be processed by injection or compression moulding.

SARS-CoV-2 pandemic has caused a collapse of the world health systems. Now, vaccines and more effective therapies have reversed this crisis but the scenario is further aggravated by the appearance of a new pathology, occurring as SARS-CoV-2 infection consequence: the long-COVID-19. This term is commonly used to describe signs and symptoms that continue or develop after acute infection of COVID-19 up to several months. In this review, the consequences of the disease on mental health and the neurological implications due to the long-COVID are described. Furthermore, the appropriate nutritional approach and some recommendations to relieve the symptoms of the pathology are presented. Data collected indicated that in the next future the disease will affect an increasing number of individuals and that interdisciplinary action is needed to counteract it., (© 2022. The Author(s).)

3D printing of polymeric scaffolds and autologous stem cells is a promising tool for damaged facial cartilage reconstruction surgeries. To this end, suitable bioinks are needed to generate scaffolds with the required morphological and functional features. We formulated hydrogel bioinks using k-Carrageen (kC) and poly(vinyl alcohol) (PVA) in three different weight ratios. The kC gives the systems the ability to undergo rapid sol-to-gel transitions upon cooling from 60 °C and above to body temperature, while the PVA is used as rheology modifier and porogen. The latter is crosslinked after molding or printing by freeze-thaw cycling for 1 day (FT1) or 5 days (FT5). To select the most suitable formulation for 3D printing, the sol-to-gel transition and the physico-chemical, mechanical and morphological properties of obtained hydrogels were studied. Moreover, the absence of cytotoxic effects of the material on SASCs was assessed in both stemness-preserving or chondro-inductive media. Printing trials were performed to identify optimal process parameters and co-printing and post-printing seeding approaches of SASCs were evaluated. Cells were found to be viable after co-printing and also after the FT1 treatment. Viable adherent cells were also found in the FT5 system, where cells were plated after freezing and thawing treatment., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Alzheimer's disease (AD) is the most common neurodegenerative disorder in the elderly. The two cardinal neuropathological hallmarks of AD are the senile plaques, which are extracellular deposits mainly constituted by beta-amyloids, and neurofibrillary tangles formed by abnormally phosphorylated Tau ( p -Tau) located in the cytoplasm of neurons. Although the research has made relevant progress in the management of the disease, the treatment is still lacking. Only symptomatic medications exist for the disease, and, in the meantime, laboratories worldwide are investigating disease-modifying treatments for AD. In the present review, results centered on the use of peptides of different sizes involved in AD are presented.

Polymeric hydrogels are increasingly considered as scaffolds for tissue engineering due to their extraordinary resemblance with the extracellular matrix (ECM) of many tissues. As cell adhesion is a key factor in regulating important cell functions, hydrogel scaffolds are often functionalized or loaded with a variety of bioactive molecules that can promote adhesion. Interesting biomimetic approaches exploit the properties of mussel-inspired recombinant adhesive proteins. In this work, we prepared hydrogel scaffolds with a 50%w mixture of k-carrageenan (kC) and polyvinyl alcohol (PVA), by a two-step physical gelation process, and we coated them with Perna viridis foot protein-5β (Pvfp5β). The mechanical and morphological properties of hydrogels were investigated both after conditioning with typical cell culture media and also after coating with the Pvfp5β. The protein resulted strongly adsorbed onto the surface of the hydrogel and also able to penetrate in its interiors to a certain depth, mainly interacting with the kC component of the scaffold as resulted from the confocal analysis. Mouse embryonic fibroblasts NIH-3T3 were seeded on top of the hydrogels and cultured up to two weeks. The role of Pvfp5β in promoting cell adhesion, spreading and colonization of the scaffold was demonstrated., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The rapidly growing interest in the application of nanoscience in the future design of radiopharmaceuticals and the development of nanosized radiopharmaceuticals in the late 2000's, resulted in the creation of a Coordinated Research Project (CRP) by the International Atomic Energy Agency (IAEA) in 2014. This CRP entitled ' Nanosized delivery systems for radiopharmaceuticals' involved a team of expert scientist from various member states. This team of scientists worked on a number of cutting-edge areas of nanoscience with a focus on developing well-defined, highly effective and site-specific delivery systems of radiopharmaceuticals. Specifically, focus areas of various teams of scientists comprised of the development of nanoparticles (NPs) based on metals, polymers, and gels, and their conjugation/encapsulation or decoration with various tumor avid ligands such as peptides, folates, and small molecule phytochemicals. The research and development efforts also comprised of developing optimum radiolabeling methods of various nano vectors using diagnostic and therapeutic radionuclides including Tc-99m, Ga-68, Lu-177 and Au-198. Concerted efforts of teams of scientists within this CRP has resulted in the development of various protocols and guidelines on delivery systems of nanoradiopharmaceuticals, training of numerous graduate students/post-doctoral fellows and publications in peer reviewed journals while establishing numerous productive scientific networks in various participating member states. Some of the innovative nanoconstructs were chosen for further preclinical applications-all aimed at ultimate clinical translation for treating human cancer patients. This review article summarizes outcomes of this major international scientific endeavor.

The aim of the present work is the characterization of biscuit doughs enriched with pomegranate peel powder (PPP) at 3 (PPP3) and 5 (PPP5) wt% in the prospect of developing a fortified aliment as a support of the therapy of chronic inflammatory diseases of the intestinal tract. The total phenolic content of the powder was preliminarily evaluated. Then, the main compounds present in the PPP were identified by HPLC-ESI-TOF-MS analysis, being mainly hydrolysable tannins. The PPP was then treated at 180 °C for 20 min to mimic the baking treatment, and its water-soluble fraction (PPPwsf) was then added in the Caco-2 cell culture as a model of the intestinal epithelial barrier to verify its dose-dependent toxicity, ability in counteracting the oxidative stress, and anti-inflammatory action. Rheological experiments were performed to predict the macroscopic behavior of the PPP-added doughs during lamination and biscuit baking. SEM investigations gave their contribution to the microscopic comprehension of the dough structure. Finally, a consumer panel composed by thirty volunteers was enrolled to express its opinion on the sensory agreeableness of the biscuits prepared with two different concentrations of PPP compared with the reference dough. The discussion is focused on the biological effects of the main components found in the PPP.

Cartilage or bone regeneration approaches based on the direct injection of mesenchymal stem cells (MSCs) at the lesion site encounter several challenges, related to uncontrolled cell spreading and differentiation, reduced cell viability and poor engrafting. This work presents a simple and versatile strategy based on the synergic combination of in-situ forming hydrogels and spheroids of adipose stem cells (SASCs) with great potential for minimally invasive regenerative interventions aimed to threat bone and cartilage defects. Aqueous dispersions of partially degalactosylated xyloglucan (dXG) are mixed with SASCs derived from liposuction and either a chondroinductive or an osteoinductive medium. The dispersions rapidly set into hydrogels when temperature is brought to 37 °C. The physico-chemical and mechanical properties of the hydrogels are controlled by polymer concentration. The hydrogels, during 21 day incubation at 37 °C, undergo significant structural rearrangements that support cell proliferation and spreading. In formulations containing 1%w dXG cell viability increases up to 300% for SASCs-derived osteoblasts and up to 1000% for SASCs-derived chondrocytes if compared with control 2D cultures. The successful differentiation into the target cells is supported by the expression of lineage-specific genes. Cell-cell and cell-matrix interactions are also investigated. All formulations resulted injectable, and the incorporated cells are fully viable after injection., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Hydrogel wound dressings can play critical roles in wound healing protecting the wound from trauma or contamination and providing an ideal environment to support the growth of endogenous cells and promote wound closure. This work presents a self-assembling hydrogel dressing that can assist the wound repair process mimicking the hierarchical structure of skin extracellular matrix. To this aim, the co-assembly behaviour of a carboxylated variant of xyloglucan (CXG) with a peptide amphiphile (PA-H3) has been investigated to generate hierarchical constructs with tuneable molecular composition, structure, and properties. Transmission electron microscopy and circular dichroism at a low concentration shows that CXG and PA-H3 co-assemble into nanofibres by hydrophobic and electrostatic interactions and further aggregate into nanofibre bundles and networks. At a higher concentration, CXG and PA-H3 yield hydrogels that have been characterized for their morphology by scanning electron microscopy and for the mechanical properties by small-amplitude oscillatory shear rheological measurements and compression tests at different CXG/PA-H3 ratios. A preliminary biological evaluation has been carried out both in vitro with HaCat cells and in vivo in a mouse model., (© The Author(s) 2021. Published by Oxford University Press.)

Bio-hybrid hydrogels consist of a water-swollen hydrophilic polymer network encapsulating or conjugating single biomolecules, or larger and more complex biological constructs like whole cells. By modulating at least one dimension of the hydrogel system at the micro- or nanoscale, the activity of the biological component can be extremely upgraded with clear advantages for the development of therapeutic or diagnostic micro- and nano-devices. Gamma or e-beam irradiation of polymers allow a good control of the chemistry at the micro-/nanoscale with minimal recourse to toxic reactants and solvents. Another potential advantage is to obtain simultaneous sterilization when the absorbed doses are within the sterilization dose range. This short review will highlight opportunities and challenges of the radiation technologies to produce bio-hybrid nanogels as delivery devices of therapeutic biomolecules to the target cells, tissues, and organs, and to create hydrogel patterns at the nano-length and micro-length scales on surfaces.

Three-dimensional spheroidal cell aggregates of adipose stem cells (SASCs) are a distinct upstream population of stem cells present in adipose tissue, with enhanced regeneration properties in vivo. The preservation of the 3D structure of the cells, from extraction to administration, can be a promising strategy to ensure optimal conditions for cell viability and maintenance of stemness potential. With this aim, an artificial niche was created by incorporating the spheroids into an injectable, in-situ gelling solution of partially degalactosylated xyloglucan (dXG) and an ad hoc formulated culture medium for the preservation of stem cell spheroid features. The evolution of the mechanical properties and the morphological structure of this artificial niche was investigated by small amplitude rheological analysis and scanning electron microscopy, respectively. Comparatively, systems produced with the same polymer and the typical culture medium (DMEM) used for adipose stem cell (ASC) growth in adherent cell culture conditions were also characterised. Cell viability of both SASCs and ASCs incorporated inside the hydrogel or seeded on top of the hydrogel were investigated as well as the preservation of SASC stemness conditions when embedded in the hydrogel., Competing Interests: Declaration of competing interest There are no conflicts to declare., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Hydrogels for complex and chronic wound dressings must be conformable, absorb and retain wound exudates and maintain hydration. They can incorporate and release bioactive molecules that can accelerate the healing process. Wound dressings have to be in contact with the wound and epidermis, even for long periods, without causing adverse effects. Hydrogel dressing formulations based on biopolymers derived from terrestrial or marine flora can be relatively inexpensive and well tolerated. In the present article hydrogel films composed by agarose (1.0 wt%), κ-carrageenan at three different concentrations (0.5, 1.0 and 1.5 wt%) and glycerol (3.0 wt%) were prepared without recourse to crosslinking agents, and characterized for their mechanical properties, morphology, swelling and erosion behavior. The films resulted highly elastic and able to absorb and retain large amounts of fluids without losing their integrity. One of the films was loaded with the aqueous extract from Cryphaea heteromalla (Hedw.) D. Mohr for its antioxidant properties. Absence of cytotoxicity and ability to reduce the oxidative stress were demonstrated on NIH-3T3 fibroblast cell cultures. These results encourage further biological evaluations to assess their impact on the healing process., Competing Interests: Declaration of competing interest The authors declare no conflict of interest and that they do not have any financial and personal relationships with other people or organizations that could inappropriately influence their work., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Ionizing radiation has become the most effective way to modify natural and synthetic polymers through crosslinking, degradation, and graft polymerization. This review will include an in-depth analysis of radiation chemistry mechanisms and the kinetics of the radiation-induced C-centered free radical, anion, and cation polymerization, and grafting. It also presents sections on radiation modifications of synthetic and natural polymers. For decades, low linear energy transfer (LLET) ionizing radiation, such as gamma rays, X-rays, and up to 10 MeV electron beams, has been the primary tool to produce many products through polymerization reactions. Photons and electrons interaction with polymers display various mechanisms. While the interactions of gamma ray and X-ray photons are mainly through the photoelectric effect, Compton scattering, and pair-production, the interactions of the high-energy electrons take place through coulombic interactions. Despite the type of radiation used on materials, photons or high energy electrons, in both cases ions and electrons are produced. The interactions between electrons and monomers takes place within less than a nanosecond. Depending on the dose rate (dose is defined as the absorbed radiation energy per unit mass), the kinetic chain length of the propagation can be controlled, hence allowing for some control over the degree of polymerization. When polymers are submitted to high-energy radiation in the bulk, contrasting behaviors are observed with a dominant effect of cross-linking or chain scission, depending on the chemical nature and physical characteristics of the material. Polymers in solution are subject to indirect effects resulting from the radiolysis of the medium. Likewise, for radiation-induced polymerization, depending on the dose rate, the free radicals generated on polymer chains can undergo various reactions, such as inter/intramolecular combination or inter/intramolecular disproportionation, b-scission. These reactions lead to structural or functional polymer modifications. In the presence of oxygen, playing on irradiation dose-rates, one can favor crosslinking reactions or promotes degradations through oxidations. The competition between the crosslinking reactions of C-centered free radicals and their reactions with oxygen is described through fundamental mechanism formalisms. The fundamentals of polymerization reactions are herein presented to meet industrial needs for various polymer materials produced or degraded by irradiation. Notably, the medical and industrial applications of polymers are endless and thus it is vital to investigate the effects of sterilization dose and dose rate on various polymers and copolymers with different molecular structures and morphologies. The presence or absence of various functional groups, degree of crystallinity, irradiation temperature, etc. all greatly affect the radiation chemistry of the irradiated polymers. Over the past decade, grafting new chemical functionalities on solid polymers by radiation-induced polymerization (also called RIG for Radiation-Induced Grafting) has been widely exploited to develop innovative materials in coherence with actual societal expectations. These novel materials respond not only to health emergencies but also to carbon-free energy needs (e.g., hydrogen fuel cells, piezoelectricity, etc.) and environmental concerns with the development of numerous specific adsorbents of chemical hazards and pollutants. The modification of polymers through RIG is durable as it covalently bonds the functional monomers. As radiation penetration depths can be varied, this technique can be used to modify polymer surface or bulk. The many parameters influencing RIG that control the yield of the grafting process are discussed in this review. These include monomer reactivity, irradiation dose, solvent, presence of inhibitor of homopolymerization, grafting temperature, etc. Today, the general knowledge of RIG can be applied to any solid polymer and may predict, to some extent, the grafting location. A special focus is on how ionizing radiation sources (ion and electron beams, UVs) may be chosen or mixed to combine both solid polymer nanostructuration and RIG. LLET ionizing radiation has also been extensively used to synthesize hydrogel and nanogel for drug delivery systems and other advanced applications. In particular, nanogels can either be produced by radiation-induced polymerization and simultaneous crosslinking of hydrophilic monomers in "nanocompartments", i.e., within the aqueous phase of inverse micelles, or by intramolecular crosslinking of suitable water-soluble polymers. The radiolytically produced oxidizing species from water, •OH radicals, can easily abstract H-atoms from the backbone of the dissolved polymers (or can add to the unsaturated bonds) leading to the formation of C-centered radicals. These C-centered free radicals can undergo two main competitive reactions; intramolecular and intermolecular crosslinking. When produced by electron beam irradiation, higher temperatures, dose rates within the pulse, and pulse repetition rates favour intramolecular crosslinking over intermolecular crosslinking, thus enabling a better control of particle size and size distribution. For other water-soluble biopolymers such as polysaccharides, proteins, DNA and RNA, the abstraction of H atoms or the addition to the unsaturation by •OH can lead to the direct scission of the backbone, double, or single strand breaks of these polymers.

Injectable, in-situ forming kefiran gels have been developed for potential applications as implantable drug delivery devices or scaffolds for tissue regeneration. Concentrated solutions (4, 5 and 6%w) of kefiran, extracted from kefir grains, have been assessed in term of viscosity and injectability through G26 syringe needles, and for their ability to undergo gelation upon mixing with different alcohols. Propylene glycol (PG) has been selected as gelling agent because it ensures homogenous gelation in relatively short times (from few minutes up to 6 h). The investigation of the rheological behavior of kefiran/PG gels varying polymer concentration and temperature (25 °C and 37 °C) has provided interesting hints to support a possible gelation mechanism that accounts also for the observed influence of the alcohol type. Finally, the study of kefiran/PG gels has been complemented with the investigation on selected formulations of the swelling/degradation behavior upon immersion in isotonic buffer solution for up to 40 days at 37 °C; of the ability of the gels to retain and/or release two model molecules; and within vitro cell viability and cytotoxicity tests, to support the absence of toxic effects on cells induced by direct contact with the gels or by leached components from these gels., (Copyright © 2020 Elsevier B.V. All rights reserved.)

A new method for the numerical simulation of the radiation chemistry of aqueous polymer solutions is introduced. The method makes use of a deterministic approach combining the conventional homogeneous radiation chemistry of water with the chemistry of polymer radicals and other macromolecular species. The method is applied on single-pulse irradiations of aqueous polymer solutions. The speciation of macromolecular species accounts for the variations in the number of alkyl radicals per chain, molecular weight, and number of internal loops (as a consequence of an intramolecular radical-radical combination). In the simulations, the initial polymer molecular weight, polymer concentration, and dose per pulse (function of pulse length and dose rate during the pulse) were systematically varied. In total, 54 different conditions were simulated. The results are well in line with the available experimental data for similar systems. At a low polymer concentration and a high dose per pulse, the kinetics of radical decay is quite complex for the competition between intra- and intermolecular radical-radical reactions, whereas at a low dose per pulse the kinetics is purely second-order. The simulations demonstrate the limitations of the polymer in scavenging all the radicals generated by water radiolysis when irradiated at a low polymer concentration and a high dose per pulse. They also show that the radical decay of lower-molecular-weight chains is faster and to a larger extent dominated by intermolecular radical-radical reactions, thus explaining the mechanism behind the experimentally observed narrowing of molecular weight distributions.

Crosslinked xyloglucan-poly(vinyl alcohol) based hydrogel films are interesting materials for wound healing applications. This work focuses on the hydrolytic degradation and consequent morphological modification of a XG-PVA film and on its interaction with cells, blood, bacteria. Biocompatibility of the film was assessed in vitro by investigating different aspects, such as cell viability, oxidative stress level, mitochondrial dysfunction and specific stress biomarkers. Partial adhesiveness was demonstrated by performing different attaching assays and phalloidin staining. Hemocompatibility of XG-PVA film after interaction with blood was evaluated by using a multi-parametric approach, including human Red Blood Cells (RBC) count, hemolytic response and platelets activation. Thrombin and fibrinogen concentrations were examined as marker of the coagulation cascade. After direct contact with human blood and peripheral blood mononuclear cells (PBMC), no evidence of cell defense response was observed. Antimicrobial activity of XG-PVA film was tested against Escherichia coli (E.coli). XG-PVA film promotes bacterial retentivity and provides mechanical protection against bacterial infiltration. After loading the film with ampicillin, an inhibitory E. coli growth zone was observed. All together these results indicate that the XG-PVA system is a promising material to be tested in vivo for wound healing applications., (Copyright © 2018. Published by Elsevier B.V.)

In wound dressing applications, exudate absorption and retention are important properties. The data presented here assess the ability of the crosslinked xyloglucan-poly(vinyl alcohol) hydrogel films (XG-PVA), described in "Xyloglucan-based hydrogel films for wound dressing: Structure-property relationships" (Ajovalasit et al., 2018) [1] and "Biocompatibility, hemocompatibility and antimicrobial properties of xyloglucan-based hydrogel film for wound healing application" (Picone et al., 2019), to absorb and retain proteins. These properties were investigated by Comassie blue staining and electrophoresis of Fetal Serum Proteins.

Recent evidences suggest that insulin delivery to the brain can be an important pharmacological therapy for some neurodegenerative pathologies, including Alzheimer disease (AD). Due to the presence of the Blood Brain Barrier, a suitable carrier and an appropriate route of administration are required to increase the efficacy and safety of the treatment. Here, poly(N-vinyl pyrrolidone)-based nanogels (NG), synthetized by e-beam irradiation, alone and with covalently attached insulin (NG-In) were characterized for biocompatibility and brain delivery features in a mouse model. Preliminarily, the biodistribution of the "empty" nanocarrier after intraperitoneal (i.p.) injection was investigated by using a fluorescent-labeled NG. By fluorescence spectroscopy, SEM and dynamic light scattering analyses we established that urine clearance occurs in 24h. Histological liver and kidneys inspections indicated that no morphological alterations of tissues occurred and no immunological response was activated after NG injection. Furthermore, after administration of the insulin-conjugated nanogels (NG-In) through the intranasal route (i.n.) no alteration or immunogenic response of the nasal mucosa was observed, suggesting that the formulation is well tolerated in mouse. Moreover, an enhancement of NG-In delivery to the different brain areas and of its biological activity, measured as Akt activation levels, with reference to free insulin administration was demonstrated. Taken together, these results indicate that the synthesized NG-In enhances brain insulin delivery upon i.n. administration and strongly encourage its further evaluation as therapeutic agent against some neurodegenerative diseases., (Copyright © 2017. Published by Elsevier B.V.)

Thin xyloglucan-based hydrogel films have been synthetized and characterized in the prospect of producing wound dressings. Polyvinyl alcohol (PVA) and glycerol (Gro) were added to have an optimal combination of softness, conformability and resilience. Physical hydrogels have been transformed into permanent covalent hydrogels by reaction with glutaraldehyde (GA). Network structure-process-property relationships are discussed on the account of the results of several complementary characterizations: FTIR, rheology, thermal analysis, morphological analysis, moisture retention and swelling measurements. Selected formulations were also subjected to preliminary in vitro cytotoxicity tests. The physical and mechanical properties of some of the xyloglucan-based hydrogel films produced, combined with absence of cytotoxicity, make them suitable candidates for integration with sensors to monitor the wound healing process and further biological investigations in animal models., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Administered by an oral route, Furosemide (FUR), a diuretic used in several edematous states and hypertension, presents bioavailability problems, reported as a consequence of an erratic gastrointestinal absorption due to various existing polymorphic forms and low and pH-dependent solubility. A mucoadhesive sublingual fast-dissolving FUR based film has been developed and evaluated in order to optimize the bioavailability of FUR by increasing solubility and guaranteeing a good dissolution reproducibility. The Differential Scanning Calorimetry (DSC) analyses confirmed that the film prepared using the solvent casting method entrapped FUR in the amorphous state. As a solid dispersion, FUR increases its solubility up to 28.36 mg/mL. Drug content, thickness, and weight uniformity of film were also evaluated. The measured Young's Modulus, yield strength, and relative elongation of break percentage (EB%) allowed for the classification of the drug-loaded film as an elastomer. Mucoadhesive strength tests showed that the force to detach film from mucosa grew exponentially with increasing contact time up to 7667 N/m². FUR was quickly discharged from the film following a trend well fitted with the Weibull kinetic model. When applied on sublingual mucosa, the new formulation produced a massive drug flux in the systemic compartment. Overall, the proposed sublingual film enhances drug solubility and absorption, allowing for the prediction of a rapid onset of action and reproducible bioavailability in its clinical application., Competing Interests: The authors declare no conflict of interest.

Poly(N-vinyl pyrrolidone)-based-nanogels (NGs), produced by e-beam irradiation, are conjugated with monoclonal antibodies (mAb) for active targeting purposes. The uptake of immuno-functionalized nanogels is tested in an endothelial cell line, ECV304, using confocal and epifluorescence microscopy. Intracellular localization studies reveal a faster uptake of the immuno-nanogel conjugate with respect to the 'bare' nanogel. The specific internalization pathway of these immuno-nanogels is clarified by selective endocytosis inhibition experiments, flow cytometry and confocal microscopy. Active targeting ability is also verified by conjugating a monoclonal antibody which recognizes the αvβ3 integrin on activated endothelial cells. Epifluorescence images of the 'wound healing assay' on ECV304 cells provide evidence of nanogels localization only in the target cells. Therefore, the immuno-nanogels produced have the potential to recognize specific cell types in heterogeneous systems, which makes them promising candidates for targeted drug delivery applications.

The development of growth factors is very promising in the field of tissue regeneration but specifically designed formulations have to be developed in order to enable such new biological entities (NBEs). In particular, the range of therapeutic concentrations is usually very low compared to other active proteins and the confinement in the target site can be of crucial importance. In-situ forming scaffolds are very promising solutions for minimally invasive intervention in cartilage reconstruction and targeting of NBEs. In this work injectable, in-situ forming gels of a temperature responsive partially degalactosylated xyloglucan (Deg-XG) incorporating the growth factor FGF-18 are formulated and characterized. In particular, injectability and shear viscosity at room temperature, time-to-gel at body temperature, morphology and mechanical properties of gels are investigated. The highly hydrophobic growth factor is favorably incorporated and retained by the gel. Gels undergo a slow erosion process when immersed in PBS at 37°C that opens up their porous structure. The prolonged hydrothermal treatment leads to structural rearrangements towards tougher networks with increased dynamic shear modulus. Preliminary biological evaluations confirm absence of cytotoxicity and the ability of these scaffolds to host cells and promote their proliferation., (Copyright © 2016 Elsevier B.V. All rights reserved.)

(1) Background: A new family of nanosystems able to discern between normal and tumor cells and to release a therapeutic agent in controlled way were synthetized by e-beam irradiation. This technique permits to obtain biocompatible, sterile, carboxyl-functionalized polyvinylpyrrolidone (PVP-co-acrylic acid) nanogels (NGs); (2) Methods: Here, we performed a targeting strategy based on the recognition of over-expressed proteins on tumor cells, like the folate receptor. The selective targeting was demonstrated by co-culture studies and flow cytometry analysis, using folate conjugated NGs. Moreover, nanoparticles were conjugated to a chemotherapeutic drug or to a pro-apoptotic siRNA through a glutathione sensitive spacer, in order to obtain a controlled release mechanism, specific for cancer cells. The drug efficiency was tested on tumor and healthy cells by flow cytometric analysis, confocal and epifluorescence microscopy and cytotoxicity assay; the siRNA effect was investigated by RNAi experiment; (3) Results: The data obtained showed that the use of NGs permits a faster cargo release in cancer cells, in response to high cytosolic glutathione level, also improving their efficacy; (4) Conclusion: The possibility of releasing biological molecules in a controlled way and to recognize a specific tumor target allows overcoming the typical limits of the classic cancer therapy.

Partially degalactosylated xyloglucan from tamarind seeds (Deg-XG) is a very appealing biopolymer for the production of in situ gelling systems at physiological temperature. In this work, we observe that the morphology of hydrogels evolves towards high degrees of structural organization with time, yielding to dense stacks of thin membranes within 24h of incubation at 37°C. We also explore the possibility offered by gamma irradiation of controlling the time scale of this phenomenon, the final morphology and mechanical properties of the system. Structural and molecular modifications of Deg-XG with dose are investigated by FTIR, dynamic light scattering (DLS) and rotational viscosimetry. The impact on gelation ability and gel strength is studied by rheological analysis. The morphology evolution is investigated by SEM analysis, and absence of cytotoxicity verified by MTS assay and optical microscopy of neuroblastoma cells., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Nanogels combine the favourable properties of hydrogels with those of colloids. They can be soft and conformable, stimuli-responsive and highly permeable, and can expose a large surface with functional groups for conjugation to small and large molecules, and even macromolecules. They are among the very few systems that can be generated and used as aqueous dispersions. Nanogels are emerging materials for targeted drug delivery and bio-imaging, but they have also shown potential for water purification and in catalysis. The possibility of manufacturing nanogels with a simple process and at relatively low cost is a key criterion for their continued development and successful application. This paper highlights the most important structural features of nanogels related to their distinctive properties, and briefly presents the most common manufacturing strategies. It then focuses on synthetic approaches that are based on the irradiation of dilute aqueous polymer solutions using high-energy photons or electron beams. The reactions constituting the basis for nanogel formation and the approaches for controlling particle size and functionality are discussed in the context of a qualitative analysis of the kinetics of the various reactions.

A growing body of evidence shows the protective role of insulin in Alzheimer's disease (AD). A nanogel system (NG) to deliver insulin to the brain, as a tool for the development of a new therapy for Alzheimer's Disease (AD), is designed and synthetized. A carboxyl-functionalized poly(N-vinyl pyrrolidone) nanogel system produced by ionizing radiation is chosen as substrate for the covalent attachment of insulin or fluorescent molecules relevant for its characterization. Biocompatibility and hemocompatibility of the naked carrier is demonstrated. The insulin conjugated to the NG (NG-In) is protected by protease degradation and able to bind to insulin receptor (IR), as demonstrated by immunofluorescence measurements showing colocalization of NG-In(FITC) with IR. Moreover, after binding to the receptor, NG-In is able to trigger insulin signaling via AKT activation. Neuroprotection of NG-In against dysfunction induced by amyloid β (Aβ), a peptide mainly involved in AD, is verified. Finally, the potential of NG-In to be efficiently transported across the Blood Brain Barrier (BBB) is demonstrated. All together these results indicate that the synthesized NG-In is a suitable vehicle system for insulin deliver in biomedicine and a very promising tool to develop new therapies for neurodegenerative diseases., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Controlled synthesis of nanoscalar and nanostructured materials enables the development of novel functional materials with fine-tuned optical, mechanical, electronic, magnetic, conductive and catalytic properties that are of use in numerous applications. These materials have also found their potential use in medicine as vehicles for drug delivery, in diagnostics or in combinations thereof. In principle, nanoparticles can be divided into two broad categories, organic and inorganic nanoparticles. For both types of nanoparticles there are numerous possible synthetic routes. Considering the large difference in nature of these materials and the elementary reactions involved in the synthetic routes, most manufacturing techniques are complex and only suitable for one type of particle. Interestingly, radiation chemistry, i.e., the use of ionizing radiation from radioisotopes and accelerators to induce nanomaterials or chemical changes in materials, has proven to be a versatile tool for controlled manufacturing of both organic and inorganic nanoparticles. The advantages of using radiation chemistry for this purpose are many, such as low energy consumption, minimal use of potentially harmful chemicals and simple production schemes. For medical applications one more advantage is that the material can be sterile as manufactured. Radiation-induced synthesis can be carried out in aqueous systems, which minimizes the use of organic solvents and the need for separation and purification of the final product. The radiation chemistry of water is well known, as are the various ways of fine-tuning the reactivity of the system towards a desired target by adding different solutes. This, in combination with the controllable and adjustable irradiation process parameters, makes the technique superior to most other chemical methods. In this review, we discuss the fundamentals of radiation chemistry and radiation-induced synthesis of nanoparticles in aqueous solutions. The impact of dose and dose rate as well as of controlled addition of various solutes on the final particle composition, size and size distribution are described in detail and discussed in terms of reaction mechanism and kinetics.

Injectable polymer scaffolds are particularly attractive for guided tissue growth and drug/cell delivery with minimally invasive intervention. In the present work, "all-polymeric" gelling systems based on pectins and water-soluble maltose-conjugated chitosans (CM) have been developed. Maltose-conjugated chitosan has been synthesized at three different molar ratios, as evaluated by FITR analysis and fluorimetric titration. A thorough rheological characterization of the blends and their parent solutions has been performed. Macroscopic gelation has been achieved by mixing the high esterification degree pectins with CM at higher maltose grafted to chitosan contents. Gels form in a few minutes and reach their full strength in less than two hours. These features encourage their further development as scaffold for tissue engineering., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

A scalable, single-step, synthetic approach for the manufacture of biocompatible, functionalized micro- and nanogels is presented. In particular, poly(N-vinyl pyrrolidone)-grafted-(aminopropyl)methacrylamide microgels and nanogels were generated through e-beam irradiation of PVP aqueous solutions in the presence of a primary amino-group-carrying monomer. Particles with different hydrodynamic diameters and surface charge densities were obtained at the variance of the irradiation conditions. Chemical structure was investigated by different spectroscopic techniques. Fluorescent variants were generated through fluorescein isothiocyanate attachment to the primary amino groups grafted to PVP, to both quantify the available functional groups for bioconjugation and follow nanogels localization in cell cultures. Finally, a model protein, bovine serum albumin, was conjugated to the nanogels to demonstrate the attachment of biologically relevant molecules for targeting purposes in drug delivery. The described approach provides a novel strategy to fabricate biohybrid nanogels with a very promising potential in nanomedicine.

Objective: The identification of precancerous lesions is the basis of an early diagnosis, and of a treatment that allows, in the great part of cases, the preservation of organ functions. The aims of this study were: the evaluation of the less invasive treatment for precancerous lesion of the larynx to minimize the recurrences, the estimation of number of further operation required., Methods: A prospective study was done on patients with clinical diagnosis of laryngeal precancerosis. The patients were treated by a transoral endoscopic approach with direct microlaryngoscopy (DML) doing an excision-biopsy with cold blade, consisting in excision of the whole visible lesion with vocal ligament preservation., Results: A recurrence of a clinically evident precancerous lesion was present in 13.2% of patients that had a laryngeal intraepithelial lesion (LIN) 1 lesion and in 28.95% of patients that had a LIN 2 lesion., Conclusion: In order to achieve a control of a precancerous lesion, we suggest: excisional biopsy/subepithelial cordectomy (type 1 cordectomy) for LIN 1 lesions and subligament cordectomy (type 2 cordectomy) in case of LIN 2 cases. In case of recurrences of LIN 1 lesion we suggest directly a type 2 cordectomy., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Bilateral vocal cord paralysis is a serious illness requiring emergency intervention to resolve the potentially life-threatening respiratory distress. Several surgical procedures were proposed to help improve the airway and to eliminate the tracheostoma in those patients with permanent paralysis. All the procedures have their own advantages and disadvantages. We conducted a retrospective study of 30 patients affected by bilateral vocal cord paralysis following total thyroidectomy. All the patients underwent total thyroidectomy for benign thyroid pathology. In 26 patients (86.6%), cord paralysis occurred during the perioperative stage; and in the remaining 4 cases (13.3%), it occurred within the following 6 months. We treated all these bilateral recurrent laryngeal nerve paralysis patients with arytenoidectomy alone in 5 patients and arytenoidectomy with concomitant true and false posterior cordectomy in the remaining 25 patients. Twenty-four of the 25 patients who underwent the combined procedures (96%) reported subjective respiratory improvement and were decannulated within 60 days, being able to return to their normal daily activities. This study demonstrates that arytenoidectomy associated with posterior cordectomy is a satisfactory surgical treatment of bilateral vocal cord paralysis because it leads to a considerable and stable enlargement of the breathing space., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Unlabelled: Primary malignant lymphomas in the salivary glands are relatively rare. Clinical presentation is not characteristic and the disease is often overlooked resulting in diagnosis and treatment delays., Aim: To stress the importance of the diagnostic process and combined management, we present a series of eight patients with malignant lymphoma of the parotid who were diagnosed only after surgery and managed with radiation and chemotherapy., Methods: Retrospective series of patients with primary malignant lymphoma of the parotid gland managed with radiotherapy and diagnostic surgical partial resection., Results: After treatment completion we achieved a loco-regional control rate of 87.5%. Toxicity was charted according to the Common Toxicity Criteria and it was seen in six patients (75%). Six patients are still alive without evidence of recurrent disease in their last follow-up., Conclusion: Our study confirms that primary early stage Non-Hodgkin Lymphoma of the parotid gland is a disease with an excellent prognosis and a good local control rate, with minimal morbidity.

Objective: Evaluation of clinical and oncological safety of the modified fronto-lateral laryngectomy in the treatment of T1a-b glottic cancer., Methods: Retrospective review of charts of patients managed with classical fronto-lateral laryngectomy or with our modified technique using a cervical fascia flap and a false cord flap to reconstruct the defect., Results: No recurrence of cancer was observed in the present series and slight dysphonia was present in all cases. The patients managed with classical technique required a revision surgery for granulations or anterior synechia in 4 cases; those managed with modified technique did not need a second intervention., Conclusion: The fronto-lateral laryngectomy should be present in the head-neck surgeon armamentarium. In T1a-b glottic cancer this technique gives a good oncological resection, but the postoperative period requires an intensive rehabilitation process. The modification of the classical technique reduces the incidence of a second intervention., (Copyright 2009 Elsevier Ireland Ltd. All rights reserved.)

Objective: The classical teaching advocates a conservative approach for children presenting with various naso-septal deformities. It may not be appropriate especially when it causes nasal obstruction to the growing child. This study has two main purposes: to contribute in identifying the correct selection criteria for surgical management of pediatric patients and in selecting the most appropriate surgical technique., Material and Method: We reviewed a series of 46 cases of post-traumatic septal and naso-septal deformity not managed promptly or with recurrence of nasal deviation, following bones fracture correction alone. The mean follow-up was 10 years., Results: Patients with naso-septal deformity managed only by septoplasty had accentuation of nasal pyramid deformity; those treated by septorhinoplasty showed a good aesthetic and functional result after long-term follow-up., Conclusion: Our series results demonstrated that the best results were obtained when we correct all evident alterations of nasal septum and pyramid at a single stage. Unsuccessful results seen in our first group suggest that immediate correction of septum alone with delayed management of nasal pyramid deformity leads to a poorer outcome.

Conclusion: Our experience confirms that pectoralis major flap is the first-choice technique for repairing recurrent hypopharyngeal fistulae in previously irradiated patients in whom microsurgical techniques are not indicated, and that hyperbaric oxygen therapy helps to solve this complex pathology., Objectives: A pharyngostome is a complication encountered when performing surgical operations on pharyngolaryngeal structures. The authors present their experience of treating recurrent complex pharyngostomes in previously irradiated patients in poor physical health. These patients need a simple, safe reconstruction with a low incidence of postoperative complications., Material and Methods: A pedicled pectoralis major flap was used for reconstruction: the skin side of the flap was used to restore the continuity of the pharyngeal mucosa, while the muscle was used to reconstruct the intermediate layer. The skin layer was completed by means of a free skin graft. In all cases, surgical treatment was combined with hyperbaric oxygen therapy before and after the operation., Results: A total of 10 patients, all of whom had previously undergone surgery and radiotherapy, had recurring or pluri-recurring pharyngostomes. All patients (8 males, 2 females; age range 52-80 years) had previously been affected by carcinoma of the pharyngolaryngeal region. All underwent major local Ablation together with radical neck dissection and radiotherapy. In all cases there was mucosa on the posterior wall; a musculocutaneous pectoralis major flap was used in all cases for reconstruction.

Osteomas of the paranasal sinuses are slow-growing, benign tumours most frequently found in the frontal sinus with an incidence that varies from 47% to 80% of the cases; there are often no symptoms and they are diagnosed by chance during an x-ray examination. The symptoms are usually headaches and those secondary to ocular or neurological complications. The therapy to be preferred is surgery. The authors describe a case of frontal osteoma complicated by frontal sinusitis and palpebral abscess.

Osteomas of the paranasal sinuses are slow-growing, benign tumours most frequently found in the frontal sinus with an incidence that varies from 47% to 80% of the cases; there are often no symptoms and they are diagnosed by chance during an X-ray examination. When there are symptoms, they are usually headaches and ocular or neurological complications. The treatment of choice is surgery. A case of frontal osteoma complicated by frontal sinusitis and by a palpebral abscess is described.

Unlabelled: A nasal septal abscess is usually the result of an infected hematoma of the septum. A secondary septal abscess may be the result of infections extending from any of the neighbouring tissues. The necrosis of septal cartilage may lead to nasal deformities and severe impairment of nasal patency and growth., Objectives: Assess if the drainage of the abscess and the immediate reconstruction of the destroyed nasal septum in the acute phase is the best treatment to prevent short- and long-term effect on nasal and midface growth., Methods: Three pediatric patients treated with drainage and immediate implantation of homologous bank cartilage prior to 1990 and four treated with mosaic plastic using small pieces of residual septal cartilage assembled with fibrin glue., Result: No complication were observed in the follow-up and any deformities in the long-term controls., Conclusions: The drainage and immediate reconstruction of the nasal septum are the golden standard in the treatment of the septum infected haematoma.

Four patients with mucocele of maxillary sinus, observed between 1995 and 2001, with two years' follow-up, are described. Aim of the present study was to establish whether endoscopic marsupialization of the maxillary sinus mucocele is adequate resolutive treatment without complete removal of the mucocele wall, using more invasive approaches. The surgical procedure used was endoscopic endonasal marsupialization by a middle and/or inferior meatal antrostomy. Outcome confirms that this technique is the gold standard treatment in this disorder. In fact, complete removal of the mucocele wall is not necessary thus avoiding the risk of iatrogenic lesions of neighbouring structures in the case of a bony erosion (orbital floor, posterior wall of the maxillary sinus).

We present our series of 21 patients treated since 1991 to 2000 with glottic carcinomas T1a-b with commissure extension. The surgical technique used has been frontolateral laryngectomy as Leroux-Robert in 8 cases, and in the other 13 cases we have contributed with somme variations using a piece of superficial cervical fascia to close the thyroid opening and a piece of the vestibular band for the reconstruction at the glottic level. We studied the functional and oncological results we have obtained with a minimum control of one year and maximum of seven years.

alpha, beta-Poly (N-hydroxyethyl)-DL-aspartamide solutions were cross-linked through gamma-radiation and the systems obtained were tested as matrices for drug sustained release, using cytarabine as model drug. We performed the characterization of the cross-linked polymer, both drug-loaded and unloaded. through water swelling measurements, scanning electron microscopy and X-ray analysis. Finally, we investigated the in vitro release behaviour of cytarabine.