Chitosan-based hydrogel to support the paracrine activity of mesenchymal stem cells in spinal cord injury treatment

Abstract Advanced therapies which combine cells with biomaterial-based carriers are recognized as an emerging and powerful method to treat challenging diseases, such as spinal cord injury (SCI). By enhancing transplanted cell survival and grafting, biomimetic hydrogels can be properly engineered to encapsulate cells and locate them at the injured site in a minimally invasive way. In this work, chitosan (CS) based hydrogels were developed to host mesenchymal stem cells (MSCs), since their paracrine action can therapeutically enhance the SC regeneration, limiting the formation of a glial scar and reducing cell death at the injured site. An injectable and highly permeable CS-based hydrogel was fabricated having a rapid gelation upon temperature increase from 0 to 37 °C. CS was selected as former material both for its high biocompatibility that guarantees the proper environment for MSCs survival and for its ability to provide anti-inflammatory and anti-oxidant cues. MSCs were mixed with the hydrogel solution prior to gelation. MSC viability was not affected by the CS hydrogel and encapsulated MSCs were able to release MSC-vesicles as well as to maintain their anti-oxidant features. Finally, preliminary in vivo tests on SCI mice revealed good handling of the CS solution loading MSCs during implantation and high encapsulated MSCs survival after 7 days

Hybrid injectable platforms for the in situ delivery of therapeutic ions from mesoporous glasses

Copper-containing bioactive glasses (Cu-MBGs) are attracting increasing interest as multifunctional agents for hard and soft tissue healing due to the ability of released copper ions to stimulate osteogenesis as well as angiogenesis and to impart anti-bacterial properties. The conjugation of these nanomaterials with a vehicle phase based on thermosensitive hydrogels represents an effective strategy to design non-invasive injectable devices for the in situ delivery of therapeutic ions from MBGs. In this contribution, Cu-containing MBGs were prepared by an aerosol-assisted spray-drying method (MBG_Cu 2%_SD) in the form of microspheres (surface area of ca 220m2 g−1) and through a sol-gel synthesis (MBG_Cu 2% _SG) in the form of spheroidal nanoparticles (surface area above 700m2 g−1). Both Cu-containing samples were able to release copper ions, although with different rates and percentage release. MBG_Cu 2%_SG released the total incorporated amount of Cu ions with a faster kinetics compared to MBG_Cu 2%_SD, that released approximately the 60% of copper. Cu-MBGs were incorporated with a final concentration of 20 mg/mL into a thermosensitive sol-gel system consisting of a novel amphiphilic poly(ether urethane) based on a commercialy available Poloxamer 407 (P407), with improved gelation ability, mechanical strength and stability in aqueous solution with respect to native P407. Cu-MBG-loaded hydrogels were characterised in terms of sol-to-gel transition temperature and time, injectability and stability in aqueous environment at 37 °C. The hybrid formulations showed fast gelation in physiological conditions (1 mL underwent complete sol-to-gel transition within 3–5 min at 37 °C) and injectability in a wide range of temperatures (5–37 °C) through different needles (inner diameter in the range 0.6–1.6 mm)

FIB-FESEM and EMPA results on Antoninianus silver coins for manufacturing and corrosion processes

[EN] A set of ancient Antoninianus silver coins, dating back between 249 and 274¿A.D. and minted in Rome, Galliae, Orient and Ticinum, have been characterized. We use, for the first time, a combination of nano-invasive (focused ion beam-field emission scanning electron microscopy-X-ray microanalysis (FIB-FESEM-EDX), voltammetry of microparticles (VIMP)) and destructive techniques (scanning electron microscopy (SEM-EDX) and electron microprobe analysis (EMPA)) along with non-invasive, i.e., micro-Raman spectroscopy. The results revealed that, contrary to the extended belief, a complex Ag-Cu-Pb-Sn alloy was used. The use of alloys was common in the flourishing years of the Roman Empire. In the prosperous periods, Romans produced Ag-Cu alloys with relatively high silver content for the manufacture of both the external layers and inner nucleus of coins. This study also revealed that, although surface silvering processes were applied in different periods of crisis under the reign of Antoninii, even during crisis, Romans produced Antoninianus of high quality. Moreover, a first attempt to improve the silvering procedure using Hg-Ag amalgam has been identified.Financial support was provided by Sapienza University of Rome (Ateneo funding, 2014 15) and Spanish projects CTQ2014-53736-C3-1-P and CTQ2014-53736-C3-2-P, which are supported with Ministerio de Economía, Industria y Competitividad (MINECO) and Fondo Europeo de Desarrollo Regional (ERDF) funds, as well as project CTQ2017-85317-C2-1-P supported with funds from, MINECO, ERDF and Agencia Estatal de Investigación (AEI). PhD grants of the Department of Earth Sciences, Sapienza University of Rome, are gratefully acknowledgedDomenech Carbo, MT.; Di Turo, F.; Montoya, N.; Catalli, F.; Doménech Carbó, A.; De Vito, C. (2018). 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Hyper-IgG4 disease: report and characterisation of a new disease

BACKGROUND: We highlight a chronic inflammatory disease we call 'hyper-IgG4 disease', which has many synonyms depending on the organ involved, the country of origin and the year of the report. It is characterized histologically by a lymphoplasmacytic inflammation with IgG4-positive cells and exuberant fibrosis, which leaves dense fibrosis on resolution. A typical example is idiopathic retroperitoneal fibrosis, but the initial report in 2001 was of sclerosing pancreatitis. METHODS: We report an index case with fever and severe systemic disease. We have also reviewed the histology of 11 further patients with idiopathic retroperitoneal fibrosis for evidence of IgG4-expressing plasma cells, and examined a wide range of other inflammatory conditions and fibrotic diseases as organ-specific controls. We have reviewed the published literature for disease associations with idiopathic, systemic fibrosing conditions and the synonyms: pseudotumour, myofibroblastic tumour, plasma cell granuloma, systemic fibrosis, xanthofibrogranulomatosis, and multifocal fibrosclerosis. RESULTS: Histology from all 12 patients showed, to varying degrees, fibrosis, intense inflammatory cell infiltration with lymphocytes, plasma cells, scattered neutrophils, and sometimes eosinophilic aggregates, with venulitis and obliterative arteritis. The majority of lymphocytes were T cells that expressed CD8 and CD4, with scattered B-cell-rich small lymphoid follicles. In all cases, there was a significant increase in IgG4-positive plasma cells compared with controls. In two cases, biopsies before and after steroid treatment were available, and only scattered plasma cells were seen after treatment, none of them expressing IgG4. Review of the literature shows that although pathology commonly appears confined to one organ, patients can have systemic symptoms and fever. In the active period, there is an acute phase response with a high serum concentration of IgG, and during this phase, there is a rapid clinical response to glucocorticoid steroid treatment. CONCLUSION: We believe that hyper-IgG4 disease is an important condition to recognise, as the diagnosis can be readily verified and the outcome with treatment is very good