International Center For Studies And Research In Biomedicine Icb


International Center For Studies And Research In Biomedicine Icb

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Grandi S.,University of Pavia | Cassinelli V.,University of Pavia | Bini M.,University of Pavia | Saino E.,University of Pavia | And 9 more authors.
International Journal of Artificial Organs | Year: 2011

Bioglasses are of wide interest since they spontaneously bond and integrate with living bone in the body. By varying the glass chemistry and/or by adding some dopants, it is possible to improve their clinical applications. Gold nanoparticles (Au NPs) are a well-known antibacterial agent, as well as a unique probe for sensing and imaging applications. We report on the synthesis of a 58S bioglass doped with Au NPs at two doping levels: 0.1% wt. and 1% wt. Antibacterial properties were observed on the Gram-positive Staphylococcus aureus, whereas no significant effects were found on the Gram-negative Escherichia coli. A possible mechanism of action of Au NPs towards bacteria has been described. © 2011 Wichtig Editore.

Giordano C.,Polytechnic of Milan | Saino E.,University of Pavia | Rimondini L.,University of Piemonte Orientale | Pedeferri M.P.,Polytechnic of Milan | And 5 more authors.
Colloids and Surfaces B: Biointerfaces | Year: 2011

Bacterial contamination of implanted devices is a common cause of their failure. The aim of the present study was to assess the capability of electrochemical procedures to: (a) promote the formation of anatase on the surface of commercially pure Grade 2 Ti and Ti Grade 5 (Ti6Al4V) alloy; (b) inhibit in vitro biofilm formation of Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus mutans and Porphyromonas gingivalis and oral plaque in vivo, (c) preserve favorable response of osteoblasts and fibroblasts to materials surfaces. Ti Grade 2 and Ti Grade 5 were respectively anodized at two different voltages: 90 and 130 V for pure titanium; 100 and 120 V for Ti6Al4V alloy. Surface characterization was performed by scanning electron microscopy (SEM) equipped with EDS probe, laser profilometry and X-ray diffractometry. Bacterial adhesion characterization was performed either in vitro and in vivo in patients. Osteoblast and fibroblast response was evaluated by metabolic activity assessment. The higher voltage applied in the anodization treatment of pure titanium (130 V) and Ti6Al4V alloy (120 V) surfaces, compared to the untreated pure titanium and Ti6Al4V and to lower voltage treatments, resulted in a greater decrease in bacterial attachment and biofilm formation in both in vitro and in vivo experiments. In contrast, the high voltage treatments were found to promote osteoblasts and fibroblasts proliferation. The observations indicated that the experimented high voltage anodization treatments may contribute to preserve the tissue integration and reduce bacteria colonization of titanium and titanium alloy for implantable applications. © 2011 Elsevier B.V.

Montanaro L.,Rizzoli Orthopaedic Institute | Montanaro L.,University of Bologna | Poggi A.,Rizzoli Orthopaedic Institute | Poggi A.,University of Modena and Reggio Emilia | And 8 more authors.
International Journal of Artificial Organs | Year: 2011

Extracellular DNA (eDNA) is an important biofilm component that was recently discovered. Its presence has been initially observed in biofilms of Pseudomonas aeruginosa, Streptococcus intermedius, Streptococcus mutans, then Enterococcus faecalis and staphylococci. Autolysis is the common mechanism by which eDNA is released. In P. aeruginosa eDNA is generated by lysis of a bacterial subpopulation, under control of quorum sensing system. In E. faecalis autolysis proceeds in a fratricide mode, resulting from a process similar to necrosis of eukaryotic cells. In Staphylococcus aureus autolysis originates by an altruistic suicide, i.e., a programmed cell death similar to apoptosis of eukaryotic cells. In S. aureus autolysis is mediated by murein hydrolase, while in S. epidermidis by the autolysin protein AtlE. In P. aeruginosa eDNA is located primarily in the stalks of mushroom-shaped multicellular structures. In S. aureus the crucial role of eDNA in stabilizing biofilm is highlighted by the disgregating effect of DNase I. eDNA represents an important mechanism for horizontal gene transfer in bacteria. eDNA and other microbial structural motifs are recognized by the innate immune system via the TLR family of pattern recognition receptors (PRRs). © 2011 Wichtig Editore.

Arciola C.R.,Rizzoli Orthopaedic Institute | Arciola C.R.,University of Bologna | Visai L.,University of Pavia | Visai L.,International Center For Studies And Research In Biomedicine Icb | And 6 more authors.
International Journal of Artificial Organs | Year: 2011

Staphylococcus aureus is the leading cause of infection in orthopedic implants and of osteomyelitis consequent to it. Here we focus on the wide array of virulence factors that endow S. aureus with its abilities to colonize peri-prosthesis tissues and to attack and damage them. Following an infective strategy orchestrated by agr locus, Staphylococcus aureus first deploys virulence factors for adhesion to the prosthesis and peri-prosthesis tissues and then launches its attack by delivering destructive factors. © 2011 Wichtig Editore.

Montanaro L.,Rizzoli Orthopaedic Institute | Montanaro L.,University of Bologna | Testoni F.,Rizzoli Orthopaedic Institute | Poggi A.,Rizzoli Orthopaedic Institute | And 6 more authors.
International Journal of Artificial Organs | Year: 2011

Implant-related osteomyelitis is a severe and deep infection of bone that arises and develops all around an implant. Staphylococcus aureus is the first cause of osteomyelitis, whether implant-related or not. Bone is an optimal substratum for S. aureus, since this bacterium expresses various adhesins by which can adhere to bone proteins and to the biomaterial surfaces coated with the proteins of the host extracellular matrix. S. aureus is able not only to colonize bone tissues, but also to invade and disrupt them by entering bone cells and inducing cell death and osteolysis. Here we illustrate the pathogenetic mechanisms that can explain how the osteomyelitis sets in and develops around an implant. © 2011 The Authors.

Testoni F.,Rizzoli Orthopaedic Institute | Montanaro L.,Rizzoli Orthopaedic Institute | Montanaro L.,University of Bologna | Poggi A.,Rizzoli Orthopaedic Institute | And 6 more authors.
International Journal of Artificial Organs | Year: 2011

Staphylococcus aureus is the leading etiologic agent of implant orthopedic infections. Until recently S. aureus was considered a mere extracellular pathogen; it then turned out to be able to invade eukaryotic cells. Adhesion of S. aureus to peri-prosthesis tissues represents the starting of the infection pathogenesis and the first step of the subsequent internalization of S. aureus by host cells. In the present work the experimental observations on two epidemic clinical strains differing in their adhesion pattern demonstrate the crucial role of the fibronectin-binding protein A in the internalization process and suggest that CNA and Bbp adhesins can play a synergistic role by acting in the initial adhesion of S. aureus to osteoblasts, thus favoring the subsequent FnBPA-mediated internalization. © 2011 Wichtig Editore.

Montagna M.,Foundation IRCCS Policlinico San Matteo | Montillo M.,Niguarda Hospital | Avanzini M.A.,Pediatric Hematology Oncology Unit | Tinelli C.,Clinical Epidemiology and Biometric Unit | And 8 more authors.
Haematologica | Year: 2011

Alemtuzumab serum levels and clinical response after subcutaneous administration (10 mg 3 times/week for six weeks) have been explored in 29 chronic lymphocytic leukemia patients receiving the monoclonal antibody as consolidation. Serum concentrations after each administration gradually increased during the first week and more markedly during weeks 2 and 3, approaching the steady-state at week 6. Absorption continued slowly through the tissues for about 2- 3 weeks after the last administration, starting to decrease thereafter. Difference between Responders and Non-responders was statistically significant: maximal concentration (Cmax) was 1.69 μg/mL vs. 0.44 μg/mL; concentration before subcutaneous administration (Cpre-dose) on day 15 was 0.7 vs. 0.21 μg/mL, area under curve (AUC0-12h) was 11.09 vs. 2.26 μg x h/mL for Responders and Non-responders, respectively. Higher systemic exposure to alemtuzumab correlated with a better clinical response and minimal residual disease. Results suggest that an adjusted schedule according to serum level could improve clinical outcome of patients receiving subcutaneous alemtuzumab. © 2011 Ferrata Storti Foundation.

Fortunati E.,University of Perugia | Armentano I.,University of Perugia | Iannoni A.,University of Perugia | Barbale M.,Novamont S.p.A. | And 7 more authors.
Journal of Applied Polymer Science | Year: 2012

The aim of this work was to study the effect of the innovative combination of microcrystalline cellulose (MCC) and silver nanoparticles (Ag) on the poly (lactide acid) (PLA) composite properties, to modulate the PLA mechanical response and induce an antibacterial effect. The preparation and characterization of PLA-based composites with MCC and Ag nanoparticles by twin-screw extrusion followed by injection molding is reported. A film procedure was also performed to obtain PLA and PLA composite films with a thickness ranged between 20 and 60 Î. The analysis of disintegrability in composting conditions by means of visual, morphological, thermal, and chemical investigations was done to gain insights into the post-use degradation processes. Tensile test demonstrated the MCC reinforcing effect, while a bactericidal activity of silver-based composites against a Gram-negative bacteria (Escherichia coli) and a Gram-positive bacteria (Staphylococcus aureus) was detected at any time points and temperatures analyzed. Moreover, the disintegrability in composting showed that MCC is able to promote the degradation process. The combination of MCC and Ag nanoparticles in PLA polymer matrix offers promising perspectives to realize multifunctional ternary composites with good mechanical response and antibacterial effect, maintaining the optical transparency and the disintegrability, hence suitable for packaging applications. © 2011 Wiley Periodicals, Inc.

Pre D.,University of Pavia | Ceccarelli G.,University of Pavia | Gastaldi G.,University of Pavia | Asti A.,University of Pavia | And 7 more authors.
Bone | Year: 2011

Several studies have demonstrated that tissue culture conditions influence the differentiation of human adipose-derived stem cells (hASCs). Recently, studies performed on SAOS-2 and bone marrow stromal cells (BMSCs) have shown the effectiveness of high frequency vibration treatment on cell differentiation to osteoblasts. The aim of this study was to evaluate the effects of low amplitude, high frequency vibrations on the differentiation of hASCs toward bone tissue. In view of this goal, hASCs were cultured in proliferative or osteogenic media and stimulated daily at 30. Hz for 45. min for 28. days. The state of calcification of the extracellular matrix was determined using the alizarin assay, while the expression of extracellular matrix and associated mRNA was determined by ELISA assays and quantitative RT-PCR (qRT-PCR). The results showed the osteogenic effect of high frequency vibration treatment in the early stages of hASC differentiation (after 14 and 21. days). On the contrary, no additional significant differences were observed after 28. days cell culture. Transmission Electron Microscopy (TEM) images performed on 21. day samples showed evidence of structured collagen fibers in the treated samples.All together, these results demonstrate the effectiveness of high frequency vibration treatment on hASC differentiation toward osteoblasts. © 2011 Elsevier Inc.

D'Angelo F.,University of Perugia | Armentano I.,University of Perugia | Cacciotti I.,University of Rome Tor Vergata | Tiribuzi R.,University of Perugia | And 16 more authors.
Biomacromolecules | Year: 2012

In this study, we investigated whether multipotent (human-bone-marrow- derived mesenchymal stem cells [hBM-MSCs]) and pluripotent stem cells (murine-induced pluripotent stem cells [iPSCs] and murine embryonic stem cells [ESCs]) respond to nanocomposite fibrous mats of poly(l-lactic acid) (PLLA) loaded with 1 or 8 wt % of calcium-deficient nanohydroxyapatite (d-HAp). Remarkably, the dispersion of different amounts of d-HAp to PLLA produced a set of materials (PLLA/d-HAp) with similar architectures and tunable mechanical properties. After 3 weeks of culture in the absence of soluble osteogenic factors, we observed the expression of osteogenic markers, including the deposition of bone matrix proteins, in multi/pluripotent cells only grown on PLLA/d-HAp nanocomposites, whereas the osteogenic differentiation was absent on stem-cell-neat PLLA cultures. Interestingly, this phenomenon was confined only in hBM-MSCs, murine iPSCs, and ESCs grown on direct contact with the PLLA/d-HAp mats. Altogether, these results indicate that the osteogenic differentiation effect of these electrospun PLLA/d-HAp nanocomposites was independent of the stem cell type and highlight the direct interaction of stem cell-polymeric nanocomposite and the mechanical properties acquired by the PLLA/d-HAp nanocomposites as key steps for the differentiation process. © 2012 American Chemical Society.

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