Bioactive scaffolds for controlling stem cell differentiation: application in myocardial tissue engineering

The aim of this PhD thesis was to prepare bioactive scaffolds to support and guide the cardiac tissue formation from dissociated stem cells. The first step of the work was the preparation and characterization of new polymeric biomaterials for application in myocardial tissue engineering. Bioartificial polymers, blends of natural polymers and synthesised biodegradable polymers were studied. Moreover, a novel thermosensitive and bioresorbable PNIPAAm-based copolymer, to be used as injectable scaffold, was synthesized. The materials selected in the previous phase were functionalized in order to furnish bioactive scaffolds able to guide and control stem cell proliferation and differentiation, using two different approaches: surface modification of polymers using signalling peptides and Molecular Imprinting technology. Moreover, microparticles of biomimetic materials were prepared and tested as release systems of bioactive agents. Then, the scaffolds were fabricated as three-dimensional highly porous structures, through freeze-drying, and as injectable systems. Innovative scaffolds with a complex three-dimensional architecture, resembling that of cardiac extracellular matrix, were also prepared using microfabrication techniques. Finally, the results obtained during the three years of PhD course, in terms of polymeric materials preparation, functionalization strategies and scaffold fabrication techniques, were converged in the development of scaffolds with multifunctional properties for guiding stem cell plasticity for myocardial regeneration. Bioactive highly porous scaffolds with specific sites for adhesion as well as for guided differentiation were prepared. In vitro cell culture tests were performed to verify their effective capacity of guiding stem cells fate.