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						| R.U. PROF. ADRIANA BIGI - University of Bologna 
 The scientific activity of the research unit of Prof. 
						Bigi is addressed to investigate the chemical and 
						structural aspects of the biomineralization processes, 
						which can be regarded as model systems for the design 
						and development of new composite materials with possible 
						applications as biomaterials. Indeed, the 
						organic/inorganic composites synthesized by living 
						organisms often display unique and desirable 
						morphological, structural and mechanical properties, and 
						represent informative models for the design and 
						synthesis of complex functional materials.
 
 Present research interests:
 
 - Synthesis and characterization of nano- and 
						microcrystalline inorganic phases through biomimetic 
						approach
 
 - Hybrid materials constituted of calcium phosphates and 
						biological active molecules
 
 - Oriented growth of inorganic phases on functionalized 
						polymeric and metallic matrices
 
 Design and development of new biomaterials for 
						applications in the orthopaedic, dental and 
						cardiovascular surgery fields, including calcium 
						phosphate bone cements, calcium phosphate- polymers 
						composites, coatings of metallic substrates.
 
 R.U. PROF. ELISABETTA WEBER - University of 
						Siena
 
 The main topic of research of the unit of Prof. 
						Elisabetta Weber is the study of lymphatic endothelium 
						in tissue sections and in culture.
 
 The interactions of endothelial cells with the 
						extracellular matrix have been evaluated on the basis of 
						fibrillin deposition in relation to the expression of 
						Microfibril Associated Glycoprotein-1 (MAGP-1).
 
 In blood endothelial cells fibrillin deposition and 
						MAGP-1 expression correlate, whereas in lymphatic 
						endothelial cells MAGP-1 is expressed later than 
						fibrillin and in negligible amount. Since fibrillin 
						forms the scaffold for elastin deposition, a different 
						pattern of fibrillin deposition may determine the 
						specificity of elastic fibres in relation to the 
						different functional requirements of lymphatic versus 
						blood vessels.
 
 Fibrillin, produced by endothelial cells and deposited 
						in the extracellular matrix, contains an RGD group that 
						may bind integrins. These molecules, with their 
						cytoplasmic tail, trigger the activation of a cascade of 
						molecules inside the cell, including the phosphorylation 
						of FAK (Focal Adhesion Kinase), that induces the 
						reorganization of cytoskeletal b-actin and hence the 
						adaptation of cell shape to the substrate.
 
 In collaboration with Prof.R.Barbucci, director of 
						C.R.I.S.M.A., we have evaluated the interactions of 
						lymphatic endothelial cells with microstructured 
						surfaces with alternating stripes of hyaluronic acid 
						(Hyal) and aminosilanized glass obtained by the method 
						of photoimmobilization. Cells grew only on glass, 
						avoiding Hyal stripes, aligned along the stripes and 
						expressed integrins, indicating that their adhesion to 
						the substrate was integrin-mediated.
 
 In collaboration with Prof.Barbucci, we have also 
						evaluated the role of the Hyal-Cu complex on the 
						behaviour of blood and lymphatic endothelial cells on 
						striped micropatterns obtained by the 
						photoimmobilization of Hyal-Cu on aminosilanized glass. 
						Blood endothelial cells tended to migrate from glass to 
						Hyal-Cu stripes, whereas lymphatic endothelial cells did 
						not migrate on Hyal-Cu and remained on glass.
 
 R.U. PROF. MARINA ZICHE - University of Siena
 
 The laboratory of Prof. Marina Ziche focuses on research 
						of the endothelium with particular emphasis on 
						angiogenesis, one of the principal functions of this 
						tissue. Angiogenesis, a process which leads to the 
						formation of new vessels, has a relevant physiological 
						role during development and in adult life. The 
						involvement of angiogenesis in pathologies, particularly 
						cancer, but also cardiovascular and neurodegenerative 
						diseases, has sparked an intense research interest in 
						this phenomenon.
 
 The involvement of angiogenesis is crucial during tissue 
						repair and in the integration of synthetic biomaterials 
						and medical devices used for surgical and reparative 
						surgery.
 
 Since the group participated together with other CRISMA 
						groups to the FIRB 2001 project (“Technologies for the 
						nanometric manipulation of biomaterials and their 
						biomedical application”, coordinated by Prof. Barbucci), 
						the Ziche Unit studied and is studying the behaviour of 
						endothelial cells on different biomaterials provided the 
						chemist units within the project.
 
 In particular microvascular endothelial cells are used, 
						since microcirculation is the site for vascular 
						remodelling and angiogenesis. The parameters under 
						investigation are cell survival at short and long time, 
						evaluated by biochemical assays and SEM analysis, 
						parameters linked to morphology, adhesion and 
						organization of the cytoskeleton (beta-actin, tubulin, 
						integrins and extracellular matrix proteins), parameters 
						of endothelial functions (expression and activity of 
						constitutive nitric oxide synthase), parameters of 
						inflammation (inducible cycloxygenase-2). Other 
						parameters specifically associated with angiogenesis are 
						the answer to specific angiogenic factors as VEGF 
						(vascular endothelial growth factor), the transcription 
						and release of FGF-2 (fibroblast growth factor-2) and 
						matrix metalloproteinases.
 
 The Unit is completing the characterization of 
						endothelial cell behaviour on micro and nanostructured 
						surfaces (PET, glass) with different coatings to allow 
						the adhesion and growth of endothelial cells, or, on the 
						contrary, of surfaces which do not allow endothelial 
						adhesion.
 
 Other biomaterials which have been characterized by the 
						Unit and are designed for a potential use in mineralized 
						tissue (bone) repair and substitution are hydroxyapatite 
						nanocrystals and titanium alloys. Both materials have 
						been demonstrated to show a good biocompatibility for 
						endothelial cells which maintain their biological 
						functions, not acquiring proinflammatory 
						characteristics, but on the contrary a well controlled 
						proangiogenic phenotype.
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