DESIGN OF VASCULARIZABLE SCAFFOLDS FOR LARGE TISSUE ENGINEERING

The emerging field of tissue engineering is dedicated to restore, maintain or improve the functions of damaged or lost human tissues. However, despite significant successes have been achieved over the last 20 years, several challenges still remain, preventing a pervasive clinical application of tissue engineering. One of the main challenges lies in the development of scaffolding materials able to mimic the complex organization of the in vivo milieu and provide tailored stimuli for tissue growth and maturation. A fundamental aspect of this problem resides in the design of scaffolds having three-dimensional vascular architecture, able to provide optimal nutrients diffusion, supporting and maintaining viable tissue in vitro, and capable to promote vascularization after implantation. The lack of proper vascularization is currently limiting the size of the engineered tissues to smaller than clinically relevant dimensions. The aim of this PhD work, merging the study of novel biomaterials and the development of original microfabrication methods, is to create enabling technologies towards the design of innovative scaffolds for large tissues engineering. For this purpose, a library of RGD-mimetic hydrogels with controlled chemical, mechanical and biological features has been developed. The obtained hydrogels have been combined with foaming and sacrificial molding techniques to engineer customizable scaffolds with hierarchical three-dimensional architectures. These novel hydrogel scaffolds supported optimal three-dimensional cell growth and promoted in vitro vascularization in large constructs. The reported results suggest that the presented approach could represent a viable solution to scale engineered tissue to clinically relevant dimensions releasing the full potential of regenerative medicine.