Tailored gelatin-based three-dimensional sysems for bone tissue engineering

Résumé

The current Doctoral Thesis is focused on the development of three-dimensional systems for bone tissue engineering purposes. Gelatin was chosen as the main material to manufacture scaffolds capable for serving as both growth factors delivery carrier and cell-therapy support. The main physic-chemical and biological properties of this natural origin polymer, together with the recent advances in gelatin-based approaches for bone tissue engineering are presented in the Introduction part. In the first experimental work, enzymatic crosslinking of gelatin with microbial transglutaminase enzyme has been optimized and in vitro release of VEGF and BMP-2 were characterized. Biological performance of those formulations was evaluated after cell seeding. In the following study, we reinforced the gelatin-based scaffolds with hydroxyapatite and calcium sulfate. In vitro characterization and in vivo bone regeneration capacity was assessed with osteoporotic mice animal model. Reinforced gelatin systems loaded with BMP-2 promoted successful bone repair in the critical sized defects. Finally, we integrated mineralized gelatin composite and bioinspired anisotropic gelatin hydrogel in a single gradual 3D system, in order to emulate the dissimilar composition, architecture and cellular organization found in the musculoskeletal interfaces. The in vitro biological assessment was performed with human adipose-derived stem cell encapsulated within the 3D biphasic hydrogel. // The current Doctoral Thesis is focused on the development of three-dimensional systems for bone tissue engineering purposes. Gelatin was chosen as the main material to manufacture scaffolds capable for serving as both growth factors delivery carrier and cell-therapy support. The main physic-chemical and biological properties of this natural origin polymer, together with the recent advances in gelatin-based approaches for bone tissue engineering are presented in the Introduction part. In the first experimental work, enzymatic crosslinking of gelatin with microbial transglutaminase enzyme has been optimized and in vitro release of VEGF and BMP-2 were characterized. Biological performance of those formulations was evaluated after cell seeding. In the following study, we reinforced the gelatin-based scaffolds with hydroxyapatite and calcium sulfate. In vitro characterization and in vivo bone regeneration capacity was assessed with osteoporotic mice animal model. Reinforced gelatin systems loaded with BMP-2 promoted successful bone repair in the critical sized defects. Finally, we integrated mineralized gelatin composite and bioinspired anisotropic gelatin hydrogel in a single gradual 3D system, in order to emulate the dissimilar composition, architecture and cellular organization found in the musculoskeletal interfaces. The in vitro biological assessment was performed with human adipose-derived stem cell encapsulated within the 3D biphasic hydrogel.