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In the bone regeneration field, properties of 3D scaffold could be improved using cellular and their released products. Even if previously documented, poly-(lactide) (PLA) scaffolds were not thoroughly evaluated for their design-related characteristics. The aim of the study was to investigate the properties of 3D printed PLA scaffolds for bone regeneration obtained through 3D printing, evaluating the differences in terms of structural properties, in vitro and in vivo cellular responses induced by different scaffold structures. Biofabrication is to generate a construct with biological function. In particular in our reserach we describe the fully process, including printing scaffold step, in vitro culture phase and subsequently in vivo transplantation. Five porous scaffold designs (A-B-C-D-E) were fabricated from a poly-(lactide) (PLA) filament. Scaffold structural parameters, such as porosity and pore size, were measured using scanning electron microscopy, and micro-computed tomography. Nano-topographic surface features were investigated by means of atomic force microscopy. Over a 112-day period, scaffolds were hydrolytically degraded and changes in weight, pH and mechanical properties were measured during degradation. Osteogenic differentiation of hPDLSCs on different scaffold designs after 21 days of culture was measured by means of RT-PCR and Western Blot. In vivo study was performed using C57BL/6 mice and was designed in 5 different groups: - Group1: Scaffold loaded with hPDLSCs - Group2: Scaffold loaded with conditioned medium (CM) derived from hPDLSCs - Group3: Scaffold loaded with exosomes (Exo) purified from CM - Group 4: Scaffold loaded with engineered exosomes (e-Exo), exosome treated with PEI (poly ether imide) - Group5: Scaffold, used as control. Histological analysis were performed after 60 days of in vivo transplantation and morphological evaluations revealed a high bone tissue formation and osteogenic cells commitment in group 3 and 4 when compared to other groups. From these results, the cell-laden PCAMSC scaffold offers a significant advantage in the TM regeneration in a rat subacute TM perforation model. It may offer attractive opportunities in the conservative clinical treatment. This study demonstrated that scaffold of group 3 and 4 significantly improved bone tissue regeneration in animal model and successfully showed new bone deposition in situ compared to the control scaffold (group 5) and group 1 and 2. Based on the results, we believe that the bioprinted scaffold may become a novel treatment for tissue regeneration approach therapy., Italian Journal of Anatomy and Embryology, Vol. 122, No. 1 (Supplement) 2017

Cristina Guarnera, Placido Bramanti, Emanuela Mazzon IRCCS Centro Neurolesi “Bonino-Pulejo”, Messina, Italy Abstract: In the therapeutic scenario of disease-modifying therapies for relapsing–remitting multiple sclerosis, the introduction of oral agents, starting in 2010 with fingolimod, has been a huge step forward in therapeutic options due to the easier administration route. Three oral drugs fingolimod, teriflunomide, and dimethyl fumarate, which are clinically approved for the treatment of relapsing–remitting multiple sclerosis, are reviewed in this work. Results of PhaseIII clinical trials and their extension studies showed that the three oral agents significantly reduced the annualized relapse rate – a superior efficacy compared to placebo. Fingolimod 0.5 mg consistently reduced clinical relapses and brain volume loss. In all Phase III studies, teriflunomide 14mg dose showed a reduction in the risk of disability accumulation. Regarding safety profile, fingolimod had more safety issues than the other two agents. For this reason, it should be strictly monitored for risks of infections, cancers, and certain transitory effects such as irregular cardiac function, decreased lymphocyte count, and a higher level of liver enzymes. Adverse effects of teriflunomide are well characterized and can be considered manageable. The main risks marked with dimethyl fumarate were flushing and gastrointestinal events. Keywords: oral agents, comparison, efficacy, safety, relapsing-remitting multiple sclerosis

Cristina Guarnera, Placido Bramanti, Emanuela Mazzon Experimental Neurology Laboratory, IRCCS Centro Neurolesi “Bonino-Pulejo”, Via Provinciale Palermo, Contrada Casazza, Messina, Italy Abstract: Alemtuzumab is a selective humanized monoclonal antibody directed against the CD52 antigen, and has been found to be a powerful treatment for relapsing remitting multiple sclerosis. Alemtuzumab demonstrated high efficacy in several clinical studies. The risk of relapse and sustained accumulation of disability showed significant reduction in the Phase II CAMMS223 and the Phase III clinical trials CARE MS I and CARE MS II. The data presented at the 32nd Congress of the European Committee for Treatment and Research in Multiple Sclerosis confirmed these results. After completion of a 1-year treatment cycle, alemtuzumab showed a sustained effect. Although the efficacy of alemtuzumab has been widely proven, several severe adverse effects have been reported with its use. Infusion-associated reactions, increased risk of infections, and secondary autoimmunity have been associated with alemtuzumab. Autoimmune disease – mainly of the thyroid – has been reported. Immune thrombocytopenic purpura and autoimmune nephropathies have been observed less frequently. These adverse effects, given the short period of alemtuzumab marketing for relapsing remitting multiple sclerosis, require strict monitoring. Keywords: effectiveness, clinical studies, follow-up, adverse events

Background Several lines of evidence suggest the consume of natural products for cancer prevention or treatment. In particular, isothiocyanates (ITCs) exerting anti-cancer properties, have received great interest as potential chemotherapeutic agents. This study was designed to assess the anti-proliferative activities of a new preparation of Moringa oleifera-derived 4-(α-L-rhamnopyranosyloxy)benzyl ITC (moringin) complexed with alpha-cyclodextrin (moringin + α-CD; MAC) on SH-SY5Y human neuroblastoma cells. This new formulation arises in the attempt to overcome the poor solubility and stability of moringin alone in aqueous media. Methods SH-SY5Y cells were cultured and exposed to increasing concentrations of MAC (1.0, 2.5 and 5.0 μg). Cell proliferation was examined by MTT and cell count assays. The cytotoxic activity of the MAC complex was assessed by lactate dehydrogenase (LDH) assay and trypan blue exclusion test. In addition, western blotting analyses for the main apoptosis-related proteins were performed. Results Treatment of SH-SY5Y cells with the MAC complex reduced cell growth in concentration dependent manner. Specifically, MAC exhibited a potent action in inhibiting the PI3K/Akt/mTOR pathway, whose aberrant activation was found in many types of cancer. MAC was also found to induce the nuclear factor-κB (NF-κB) p65 activation by phosphorylation and its translocation into the nucleus. Moreover, treatment with MAC was able to down-regulate MAPK pathway (results focused on JNK and p38 expression). Finally, MAC was found to trigger apoptotic death pathway (based on expression levels of cleaved-caspase 3, Bax/Bcl-2 balance, p53 and p21). Conclusion These findings suggest that use of MAC complex may open novel perspectives to improve the poor prognosis of patients with neuroblastoma.