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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.