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

• Autores: Maria del Carmen Echave Otaño
• Directores de la Tesis: Gorka Orive Arroyo (dir. tes.), José Luis Pedraz Muñoz (dir. tes.)
• Lectura: En la Universidad del País Vasco - Euskal Herriko Unibertsitatea ( España ) en 2019
• Idioma: inglés
• Títulos paralelos:
  • Gelatinan oinarritutako hiru dimentsiotako sistema egokituak hezur ehunen ingeniaritzarako
• Tribunal Calificador de la Tesis: Juan Manuel Irache Garreta (presid.), Arantxazu Isla Ruiz (secret.), Paul De Vos (voc.)
• Programa de doctorado: Programa de Doctorado en Investigación y Evaluación de Medicamentos. Aplicación de la Tecnología Farmacéutica al Desarrollo de Terapias Avanzadas por la Universidad del País Vasco/Euskal Herriko Unibertsitatea
• Materias:
  • Ciencias de la vida
    • Biología celular
      • Cultivo celular
  • Ciencias médicas
    • Farmacología
      • Evaluación de medicamentos
      • Preparación de medicamentos
• Enlaces
  • Tesis en acceso abierto en: ADDI
• Resumen

  • 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.