PhD defence E. (Enrique) Andrés Sastre

Dissertation in short:

Mobility is crucial for quality of life. However, after a traumatic injury or the resection of bone tumours, patients might be left with injured bones unable to heal. During skeletal development and during the repair of bone fractures, our bodies generate transient cartilage structures to direct bone formation. By replicating those cartilage structures, new bone graft substitutes with improved properties can be designed. However, the composition of the transient cartilage and the role of its individual elements is not fully understood. Gaining more knowledge about the components of cartilage is thus, necessary to determine which ones may be useful to promote bone healing. In the first three chapters of my dissertation I studied the role that two cartilage components: Thrombospondin-4 (TSP-4) and Thrombospondin-5 (TSP-5), play in skeletal development, disease, and repair. I observed that TSP-4 and TSP-5 play slightly different roles in those processes. While the two cartilage components studied contribute to the maintenance of the cartilage, TSP-4 production naturally precedes bone formation and appears to direct bone vascularisation; this, suggest a potential use of TSP-4 for bone repair. In addition, I hypothesise that in contrast to TSP-5, the production of TSP-4 in joints affected by osteoarthritic disease might aggravate the disease in the long term. In the fourth chapter, I present a more efficient methodology for the screening of new bone grafts that could potentially reduce the number of animals used in research while also improving their welfare.