• low intensity pulsed ultrasound
• endothelial progenitor cells
• barium titanate
• small vascular grafts

This thesis focused on the development of small caliber vascular grafts. This represents an important challenge to face cardiovascular diseases, which are the leading causes of death or impaired quality of life for millions of subjects. Existing solutions are still limited by a sub-optimal biomaterial response and a rather poor re- endothelialization, once the prosthesis is implanted in vivo. The main idea behind this thesis is to pursue a new re-endothelialization strategy based on the combination of piezoelectric smart materials and ultrasound simulation. A novel small diameter (< 6 mm) elastomeric vascular graft made of poly(ether)urethane–polydimethylsiloxane doped with (0.2% w/v) barium titanate nanoparticles (BTNPs, diameter: 300 nm) was developed. The graft was fabricated through a spray, phase-inversion technique that allowed to obtain two different layers: an internal one, about 100 μm thick and featured by a high porosity and an external one, about 400 μm thick and featured by low porosity. Doped and non-doped materials were then both qualitatively and quantitatively characterized. Mechanical traction tests were performed together with Piezoelectric Force Microscopy (PFM) and atomic force microscopy (AFM). In addition, macroscopic and microscopic images of the graft surface were acquired through Scanning Electron Microscopy (SEM) and Digital Microscope Hirox. Energy Dispersive X-ray (EDX) analysis allowed to demonstrate the presence of nanoparticles within the doped material. Fibronectin and fibrin coatings were evaluated on the graft and the best solution guaranteeing optimal cell vitality was found. The cells used to this purpose were endothelial progenitor cells (EPCs), isolated from the peripheral blood of human volunteers and subsequently seeded onto the grafts. Finally, the EPC-seeded scaffolds were assembled in a custom set-up able to stimulate cells with a precisely controlled dose of low intensity pulse ultrasound stimulation (LIPUS). Future experiments will be conducted to verify by immune fluorescence and gene analysis if the EPC differentiation process can be fastened/enhanced by piezoelectric nanoparticles and LIPUS.