1,721,173 research outputs found

    Micro- to Nanoscale Bio-Hybrid Hydrogels Engineered by Ionizing Radiation

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    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

    A multifuctional nanoplatform for drug targeted delivery based on radiation-engineered nanogels

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    Under a rational design, combining biologically active molecules, ligands to specific cell receptors and fluorescent, radioactive or paramagnetic labels into a single nano-object can bridge the unique properties of the individual components and improve conventional sensing, imaging and therapeutic efficacies. The validation of these functional nano-objects requires careful testing both in terms of physico-chemical properties and biological behaviour in vitro and in vivo, prior to translation into the clinic. Ionising radiation of aqueous polymer solutions is a viable strategy to produce multifunctional nanogels from aqueous solutions of hydrophilic polymers. By proper selection of the irradiation conditions, polymer concentration and gaseous atmosphere, nanogels with the desired features in terms of dimensions, surface electric charge and chemical reactivity can be produced. In particular, radiation-engineered poly(N-vinyl pyrrolidone)-based nanogels bearing carboxyl groups and primary amines can be used as the main building block of promising theranostic nanodevices. The possibility of exploiting these functional groups to bind molecules of interest for their characterisation and biological evaluation is discussed

    E-beam crosslinked nanogels conjugated with monoclonal antibodies in targeting strategies

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    Poly(N-vinyl pyrrolidone)-based-nanogels (NGs), produced by e-beam irradiation, are conjugated with monoclonal antibodies (mAb) for the development of an effective targeting purposes. The uptake of immuno-functionalized nanogels is tested in an endothelial cell line, ECV 304, using confocal and epifluorescence microscopy. Intracellular localization studies reveal a faster uptake of the immuno-nanogel complex 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 reveals an exclusive localization of nanogels in the target cells. Thus, the immuno-nanogels have the potential to recognize specific cell types in a heterogeneous system, which makes them suitable for targeted drug delivery applications

    Biocompatibility, hemocompatibility and antimicrobial properties of xyloglucan-based hydrogel film for wound healing application

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    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

    Hydrothermal aging of carbon reinforced epoxy laminates with nanofibrous mats as toughening interlayers

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    Electrospun mats have been applied as toughening interlayers in high performance carbon fiber epoxy composites. While the toughening mechanism exerted by the mat at the interface is the subject of several recent studies, no investigations are reported on the aging behaviour of laminates comprising these nanostructured elements. This work investigates the influence of the combined effect of water and temperature (90 °C) on laminates with Nylon 6,6 electrospun membranes placed either at the middle plane only or at each interlayer. The water-uptake behaviour is modelled by a two-stage diffusion model and compared with the behaviour of the neat resin and of the laminate without mats. Interestingly, a lower water uptake is observed for the laminates with mat-modified interfaces and this is possibly due to a significantly reduced porosity. The effect of hydrothermal aging on the thermal (Tg) and mechanical properties (transverse flexural modulus and interlaminar shear strength) of the various laminates is also investigated

    Mitochondria embedded in degalactosylated xyloglucan hydrogels to improve mitochondrial transplantation

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    Mitochondria are the major source of intracellular adenosine triphosphate (ATP) and play an essential role in a plethora of physiological functions, including regulating metabolism and maintaining cellular homeostasis. Mitochondrial dysfunction is associated with the onset of several cardiovascular diseases and, although several approaches currently exist to counteract it, no treatment using mitochondria as a therapeutic target exists to date. Recently, mitochondrial transplantation (MT) has been identified as a potential therapy that leads to increased ATP production, reduced oxidative stress, and improved bioenergetics. MT involves the replacement of damaged mitochondria, following injury or diseases. With MT, mitochondria must survive an inhospitable extracellular environment often characterized by oxidizing agents due to pathological and/or inflammatory conditions. Furthermore, only a small percentage of the injected mitochondria reaches the target site due to dispersion throughout the body. In this work, an MT strategy involving degalactosylated xyloglucan hydrogel encapsulating mitochondria, to overcome MT problems and improve its efficiency, is illustrated for the treatment of cardiovascular damage. The presence of the hydrogel presents the following advantages: improves the health of mitochondria; plays a protective role towards mitochondria from the extracellular environment and oxidative stress; allows for sustained release of viable mitochondria and local transfer into host cells

    Pharmaceutical compositions in the form of gel containing xyloglucan and alcohols for the controlled release of active ingredients

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    The invention relates to gel compositions comprising pharmaceutical active ingredients. The composition comprises xyloglucan at concentration between 0.1% and 10.0% by total weight of the composition, together with a primary alcohol at a concentration between 20.0 and 50.0% by total weight of the composition. The invention also describes a process for the preparation of the composition and its use in the treatment of pathologies wherein a controlled release of the active principle is useful

    Kefiran-based scaffolds for biomedical applications

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    Kefiran is an exopolysaccharide produced by microorganisms present in kefir grains, with several health promoting properties. A optimized protocol was developed for the separation of kefiran from kefir grains, allowing to reach a yield 4÷5 % without using toxic or expensive chemicals. The capability of kefiran to produce scaffold via Thermally Induced Phase Separation (TIPS) technique was investigated and porous scaffolds structure was obtained. Separated kefiran and scaffolds were analyzed via DSC and different thermal properties between purified kefiran and scaffold were revealed. XRD analysis revealed different structure between kefiran and scaffolds. The porous scaffold structure can be modulated by modifiying the thermal path of the solution during the phase separation. The citotoxicity of kefiran was evaluated with cell viability test and a significant faster cell proliferation in the treated colture medium with kefiran was evidenced

    Physico-chemical and mechanical characterization of in-situ forming xyloglucan gels incorporating a growth factor to promote cartilage reconstruction

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    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
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