3D-printed boNes and Tendon-inspired Hierarchical Electrospun Scaffolds strategies to enhance the Enthesis regeneration via Stem cells

3NTHESES will bring together innovative additive manufacturing (AM) and electrospinning (ES) biofabrication strategies, to produce a new generation of multi-layer hierarchical multi-material scaffolds (MLHMMS) able to faithfully mimic the multiscale morphology and the mechanical performances of the enthesis tissue. MLHMMS will be designed to drive the stem cells fate. Starting from the morphological study of an animal model, several imaging techniques will be used to acquire and measure all the morphological features of the tendon, the fibrocartilage and the bone tissue. The bone images will be used to produce bone-inspired AM mineralized scaffolds that will be directly printed on ES hierarchical nanofibrous tendon-inspired partially mineralized scaffolds, reproducing the whole enthesis. The mechanical performances of the MLHMMS will be compared with the natural tissue using mechanical tests matched with imaging strain analysis. The optimized MLHMMS, will be seeded with stem cells in comparative static and dynamic cultures in bioreactor following their proliferation, differentiation in tenocyte, fibrochondrocytes, osteocytes and the production of different biological markers, using imaging and biological characterizations. Finally, the cellularized constructs will be mechanically compared with the natural tissue using biomechanical tests. The applicant (Dr. Alberto Sensini) is a research fellow in biofabrication and biomechanics. He will apply the tendon-inspired ES hierarchical scaffold, developed during his Ph.D., and his imaging/biomechanical skills to enhance the biomimicry of these constructs. Moreover, thanks to the supervision, mentoring and training activities provided by the host organization (Maastricht University) on bone AM, stem cells cultures and biological characterizations, he will complete his interdisciplinary biofabrication expert profile.