Chondrosia reniformis as source of compounds and inspiration for developing tissue engineering scaffolds

• Autores: Miguel Soares Rocha
• Directores de la Tesis: Tiago H. Silva (dir. tes.), Ángel Pérez Diz (dir. tes.)
• Lectura: En la Universidade do Minho ( Portugal ) en 2025
• Idioma: español
• Enlaces
  • Tesis en acceso abierto en: hdl.handle.net
• Resumen

  • Collagen’s properties make it an attractive material for Tissue Engineering and Regenerative Medicine. While mammalian-origin collagens remain the main industrial source, collagens derived from marine sources are gaining attention due to several advantages over their mammalian counterparts, e. g. avoidance of zoonotic risks. Chondrosia reniformis is a collagen-rich marine sponge which can be maricultured, making it a promising collagen source. In the context of blue biotechnology, this thesis aims to demonstrate the biomedical potential of C. reniformis collagen, particularly regarding the engineering of different human tissues. A first evaluation of collagen isolated from the sponge’s ectosome and choanosome revealed a cytotoxic effect of choanosome collagen on L929 cells, whereas ectosome collagen promoted cell metabolism and proliferation. Inspired by these results, the future use of ectosome-derived collagen in biomedical applications was evaluated, namely by fabricating freeze-dried and 3D-printed scaffolds. The freeze-dried genipin-crosslinked collagen scaffolds enhanced cell metabolism and proliferation of ATDC5, BJ and EA.hy926 cells, and supported ASCs’ early chondrogenic differentiation, even in basal conditions. The 3D-printed scaffolds, using inks of collagen and alginate incorporating calcium phosphates doped with strontium, presented adequate mechanical properties for bone tissue engineering and improved Saos-2 cells viability and proliferation. Envisioning the contribution for the development of an innovative collagen enzymatic crosslinking system to engineer biomimetic collagen-based biomaterials, this thesis proposes a deeper understanding of the C. reniformis stiffening phenomenon, particularly regarding the underlying molecular mechanisms and aggregation factors. High-throughput transcriptomic and proteomic approaches revealed similarities to vertebrates’ actin-myosin-based muscle contraction, not only in the modulated genes and proteins but also concerning metabolic pathways, uncovered an apparent involvement of symbionts and established the absence of homologies with echinoderms’ stiffening factors. Aligned with the principles of the blue bioeconomy and in a sustainable development framework, the versatility of this collagen as building block of distinct biomedical applications was demonstrated and the groundwork for developing novel collagen enzymatic crosslinkers was established, presenting C. reniformis as a valuable model organism for biomedicine.