Multidisciplinary strategies for total and partial tendon rupture repair: Hydrogel design and scaffold fabrication through 3D bioprinting and electrospinning techniques

• Autores: Sandra Ruiz Alonso
• Directores de la Tesis: José Luis Pedraz Muñoz (codir. tes.), Laura Saenz del Burgo Martínez (codir. tes.)
• Lectura: En la Universidad del País Vasco - Euskal Herriko Unibertsitatea ( España ) en 2024
• Idioma: inglés
• Número de páginas: 253
• Enlaces
  • Tesis en acceso abierto en: ADDI
• Resumen

  • Tendon injuries are a significant global health problem. Traditional treatments are often inadequate for effective rehabilitation. Therefore, there has been a shift towards the use of tissue engineering for tendon regeneration. The aim of this thesis was to develop advanced therapy products by combining hydrogels, 3D bioprinting, electrospinning, cell therapy and growth factor therapy to enhance tendon regeneration. Five specific objectives were outlined: (i) to develop a biomimetic hydrogel for tendon regeneration, (ii) to fabricate 3D bioprinted scaffolds with embedded cells and growth factors for the treatment of partial tendon injuries and (iii) to evaluate cell behavior, the release profiles of growth factors, and the activity of these released growth factors in vitro, (iv) to fabricate hierarchical composite scaffolds for the treatment of total tendon injuries and (v) to evaluate their mechanical properties and assess their ability to retain cells, as well as to investigate cell behavior including proliferation, gene expression activity, and other cellular responses within the scaffold. The methodology involved a literature review for the design of a biomimetic hydrogel mimicking tendon properties. This hydrogel was characterized for various applications such as 3D bioprinting and injection. Tenocyte loaded scaffolds and growth factor loaded scaffolds were 3D bioprinted using the developed hydrogel as bioink. Cell performance, release kineticsand efficacy of the released growth factors were evaluated for tendon partial rupture regeneration. Complex hierarchical scaffolds were fabricated using electrospinning and hydrogel injection. The mechanical properties and cell behavior of the embedded tenocytes were thoroughly evaluated. The results showed promising outcomes: the developed biomimetic hydrogel successfully mimicked native tendon matrix properties, the 3D printed scaffolds exhibited suitable properties for treating partial tendon injuries, biocompatibility evaluations showed good viability and activity of the embedded tenocytes and the released growth factors facilitated vascularization and cell proliferation. Composite hierarchical scaffolds exhibited enhanced biomimetic properties and improved cell behavior, providing a structure that closely resembles native tendons and providing favorable conditions for cell growth and tissue regeneration. The integration of hydrogel and electrospun fibers resulted in scaffolds with superior mechanical properties and improved elasticity, which are critical for effective tendon repair. In conclusion, this work represents a significant advancement in tendon tissue engineering, providing insights and methods to effectively treat tendon injuries and potentially improve clinical outcomes.