Tesis doctoral de Aitor Aguirre Cano
The work of this thesis owes to the necessity of developing new strategies in tissue engineering and regenerative medicine to face current challenges. Biomaterial implants for tissue repair typically fail due to poor tissue integration. This in turn is provoked by lack of vascularization, a problem that leads to accumulation of waste products, hypoxia and necrosis in the affected area. To solve this problem several different approaches are possible, but all of them agree on the basic solution, which relies on improving vascularization of the affected area. In vivo, tissues are highly vascularized -with few exceptions, such as cartilage-. The blood supply takes care of the homeostasis of the tissue, providing oxygen, nutrients, biochemical signals and removing waste products. In a sense, it would be fair to say that the vascular system and its dynamic rearrangement (vascularization, neovascularization or angiogenesis) is the solution nature found to the problem we are currently facing in regenerative medicine. to improve vascular supply to implants we must first need to understand two basic but highly sophisticated processes: 1) how cells involved in vascularization behave, their biology (and this belongs mostly to field of stem cell biology) and 2) understand how these cells interact with biomaterials, so we can tailor and modify them to obtain the best cellular response in the body, -that is to obtain the most adequate vascularizing response to the situation- (and that would belong to the fields of biomaterials science and tissue engineering). These kind of biomaterials already exist to a certain extent and are popularly known as third generation biomaterials or smart biomaterials. in the present work, we obtained endothelial progenitor cells from the bone marrow (bm-epcs) -cells which regenerate the vascular tree in adults- and studied some of their biological properties to uncover properties that could later be exploited in biomaterials design. We found out that calcium, a well-known bioactive ion, worked through a cell surface receptor to modulate these cells proangiogenic development. Furthermore, we investigated how bm-epcs intercted with other cell commonly used in regenerative strategies, mesenchymal stem cells (mscs). We found out that a complex regulation took place, affecting gene expression and tube formation, with some positive effects over angiogenesis. Later, we explored the interaction of bm-epcs with two different composite biomaterials with bioactive potential composed of poly-lactic acid, calcium phosphate glass and hyaff -a hyaluronic acid derivative-. One of these compositions was found to be proangiogenic. We characterized its effects over bm-epcs and found out that induced endothelial differentiation, chemotaxis and vascular tree formation. Further on, we studied the mechanism activated by the biomaterial that drove this effects and found out that two independet but interacting pathways were responsible. On one hand, biochemical components, such as bioactive calcium, activated signals mediating vegf production. On the other hand, mechanical signals transmitted through matrix stiffness regulated the process of vegf production and vegfr2 synthesis. Both pathways participated synergistically promoting angiogenesis. in the future, the lessons obtained from this study can be applied to biomaterials design to develop modifications better suited to promote vascularization.
Datos académicos de la tesis doctoral «Principles of vascularization in tissue engineering using endothelial progenitors and bioactive composite biomaterials«
- Título de la tesis: Principles of vascularization in tissue engineering using endothelial progenitors and bioactive composite biomaterials
- Autor: Aitor Aguirre Cano
- Universidad: Politécnica de catalunya
- Fecha de lectura de la tesis: 20/12/2010
Dirección y tribunal
- Director de la tesis
- Elisabet Engel López
- Tribunal
- Presidente del tribunal: josep antoni Planell estany
- joí«lle Vilamitjana amedee (vocal)
- (vocal)
- (vocal)