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Saviore dell'Adamello, Italy

Gerges I.,Fondazione Filarete | Gerges I.,Tensive s.r.l. | Tamplenizza M.,Fondazione Filarete | Tamplenizza M.,Tensive s.r.l. | And 15 more authors.
International Journal of Polymeric Materials and Polymeric Biomaterials | Year: 2016

A highly crosslinked composite dextran-based scaffold (named DexFoam) was tailored to overcome specific deficiencies of polymeric and ceramic bone scaffolds and to guarantee a bone-mimicking microenvironment for the proliferation of human mesenchymal stem cells in vitro. The creep resistance for up to 90% compressive stain, the capability to regain the original shape after deformation, and the good thermal stability in both physiological and “body limit” conditions make DexFoam a valid alternative to the currently available bone scaffolds. Histopathological evaluation for host reaction and tissue colonization of DexFoam scaffold, implanted subcutaneously in mice, demonstrated its in vivo biocompatibility and biodegradability. © 2016, Copyright © Taylor & Francis Group, LLC.

Frezzetti D.,IRGS Biogem S.c.ar.l. | Frezzetti D.,University of Naples Federico II | De Menna M.,SEMM | De Menna M.,Centro Of Ingegneria Genetica E Biotecnologie Avanzate | And 17 more authors.
Oncogene | Year: 2011

miR-21 is a microRNA (miRNA) frequently overexpressed in human cancers. Here we show that miR-21 is upregulated both in vitro and in vivo by oncogenic Ras, thus linking this miRNA to one of the most frequently activated oncogenes in human cancers. Ras regulation of miR-21 occurs with a delayed kinetic and requires at least two Ras downstream pathways. A screen of human thyroid cancers and non-small-cell lung cancers for the expression of miR-21 reveals that it is overexpressed mainly in anaplastic thyroid carcinomas, the most aggressive form of thyroid cancer, whereas in lung its overexpression appears to be inversely correlated with tumor progression. We also show that a LNA directed against miR-21 slows down tumor growth in mice. Consistently, a search for mRNAs downregulated by miR-21 shows an enrichment for mRNAs encoding cell cycle checkpoints regulators, suggesting an important role for miR-21 in oncogenic Ras-induced cell proliferation. © 2011 Macmillan Publishers Limited.

Martello F.,Fondazione Filarete | Tocchio A.,SEMM | Tamplenizza M.,Fondazione Filarete | Gerges I.,Fondazione Filarete | And 9 more authors.
Acta Biomaterialia | Year: 2014

Poly(amido-amine) (PAA) hydrogels containing the 2,2-bisacrylamidoacetic acid-4-amminobutyl guanidine monomeric unit have a known ability to enhance cellular adhesion by interacting with the arginin-glycin-aspartic acid (RGD)-binding αVβ3 integrin, expressed by a wide number of cell types. Scientific interest in this class of materials has traditionally been hampered by their poor mechanical properties and restricted range of degradation rate. Here we present the design of novel biocompatible, RGD-mimic PAA-based hydrogels with wide and tunable degradation rates as well as improved mechanical and biological properties for biomedical applications. This is achieved by radical polymerization of acrylamide-terminated PAA oligomers in both the presence and absence of 2-hydroxyethylmethacrylate. The degradation rate is found to be precisely tunable by adjusting the PAA oligomer molecular weight and acrylic co-monomer concentration in the starting reaction mixture. Cell adhesion and proliferation tests on Madin-Darby canine kidney epithelial cells show that PAA-based hydrogels have the capacity to promote cell adhesion up to 200% compared to the control. Mechanical tests show higher compressive strength of acrylic chain containing hydrogels compared to traditional PAA hydrogels. © 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Gerges I.,Fondazione Filarete | Gerges I.,Tensive s.r.l. | Tamplenizza M.,Fondazione Filarete | Tamplenizza M.,Tensive s.r.l. | And 10 more authors.
Macromolecular Bioscience | Year: 2016

This study presents a custom-made in situ gelling polymeric precursor for cell encapsulation. Composed of poly((2-hydroxyethyl)methacrylate-co-(3-aminopropyl)methacrylamide) (P(HEMA-co-APM) mother backbone and RGD-mimicking poly(amidoamine) (PAA) moiteis, the comb-like structured polymeric precursor is tailored to gather the advantages of the two families of synthetic polymers, i.e., the good mechanical integrity of PHEMA-based polymers and the biocompatibility and biodegradability of PAAs. The role of P(HEMA-co-APM) in the regulation of the chemico-physical properties of P(HEMA-co-APM)/PAA hydrogels is thoroughly investigated. On the basis of obtained results, namely the capability of maintaining vital NIH3T3 cell line in vitro for 2 d in a 3D cell culture, the in vivo biocompatibility in murine model for 16 d, and the ability of finely tuning mechanical properties and degradation kinetics, it can be assessed that P(HEMA-co-APM)/PAAs offer a cost-effective valid alternative to the so far studied natural polymer-based systems for cell encapsulation. (Figure presented.) . © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

Rossi E.,SEMM | Rossi E.,University of Basel | Rossi E.,University of Milan | Gerges I.,Filarete Foundation | And 12 more authors.
Biomaterials | Year: 2016

Despite clinical treatments for adipose tissue defects, in particular breast tissue reconstruction, have certain grades of efficacy, many drawbacks are still affecting the long-term survival of new formed fat tissue. To overcome this problem, in the last decades, several scaffolding materials have been investigated in the field of adipose tissue engineering. However, a strategy able to recapitulate a suitable environment for adipose tissue reconstruction and maintenance is still missing. To address this need, we adopted a biologically and mechanically driven design to fabricate an RGD-mimetic poly(amidoamine) oligomer macroporous foam (OPAAF) for adipose tissue reconstruction. The scaffold was designed to fulfil three fundamental criteria: capability to induce cell adhesion and proliferation, support of in vivo vascularization and match of native tissue mechanical properties. Poly(amidoamine) oligomers were formed into soft scaffolds with hierarchical porosity through a combined free radical polymerization and foaming reaction. OPAAF is characterized by a high water uptake capacity, progressive degradation kinetics and ideal mechanical properties for adipose tissue reconstruction. OPAAF's ability to support cell adhesion, proliferation and adipogenesis was assessed in vitro using epithelial, fibroblast and endothelial cells (MDCK, 3T3L1 and HUVEC respectively). In addition, in vivo subcutaneous implantation in murine model highlighted OPAAF potential to support both adipogenesis and vessels infiltration. Overall, the reported results support the use of OPAAF as a scaffold for engineered adipose tissue construct. © 2016 Elsevier Ltd

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