New processing and applications of collagen containing calcium phosphate cements
- Autores: Román Pérez Antoñanzas
- Directores de la Tesis: Maria Pau Ginebra i Molins (dir. tes.)
- Lectura: En la Universitat Politècnica de Catalunya (UPC) ( España ) en 2011
- Idioma: inglés
- Tribunal Calificador de la Tesis: Francisco Javier Gil Mur (presid.), Cristina Canal Barnils (secret.), Nicholas Dunne Dunne (voc.), George Altankov (voc.), Jordi Franch Serracanta (voc.)
- Materias:
- Enlaces
- Tesis en acceso abierto en: TDX
- Resumen
When bone regeneration is needed, natural bone grafts are widely used. They are the best option since they present the same composition to that of bone, contain living cells with osteogenic potential, growth factors that induce cell differentiation into osteoblasts and extracellular matrix proteins that facilitate bone healing. However, this system presents some drawbacks, such as pain, morbidity, possible transmission of diseases in some cases, as well as limited availability. That is why synthetic bone grafts are one of the main objectives of the research in regenerative medicine and tissue engineering. This new discipline is based on the development of new biomaterials and on the comprehension of the interactions between the cells and the material in order to enhance the bone healing response. The present thesis is focused on calcium phosphate cements-based materials. CPC have the ability to transform an injectable paste made of calcium phosphates, into a phase similar to that of bone, hydroxyapatite. The CPC are well known for their osteoconductive properties. Nevertheless, these may be improved from a biological point of view and can be further processed to obtain materials with new morphologies and different applications. Therefore, the incorporation of collagen in these CPC was though as a way to enhance their biological performance. Furthermore, new processing approaches were studied, as well as their applications in new fields. The thesis is divided in three main parts: i) injectable composite cements; ii) composite macroporous scaffolds for tissue engineering and iii) composite microcarriers. In the first part, the fabrication of injectable composite cements is described as well their physico-chemical and morphological features. It is observed that the setting reaction is delayed in the presence of collagen during the initial minutes of reaction. Already after 1 hour the kinetics are similar in the presence and absence of collagen, without affecting the final product of reaction. The presence of collagen increases the injectability of the cements, whereas the mechanical properties decrease as the collagen concentration increases. From a biological point of view, the addition of collagen results in an increase in the initial cell adhesion as well as an increase in the cell proliferation rates. In the second part, macroporous scaffolds made of collagen and CPC are fabricated. These scaffolds are prepared through the freeze-drying of a collagen-CPC slurry. Different amounts of CPC are incorporated in the scaffolds. When mesenchymal stem cells are cultured on these scaffolds, it is observed that as the CPC content increases in the scaffolds, the cell differentiation increases, whereas the proliferation decreases. Further improvement of the scaffolds can be achieved though the incorporation of a BMP-7 gene into the scaffolds, in order to stimulate their osteoinductivity. The results show that as the gene incorporated in the scaffolds increases, there is an increase in the BMP-7 production, although this increase is associated with an increase in cell proliferation. In the third and final part, spherical microcarriers containing either gelatin or collagen are produced through the setting reaction of the CPC in a water in oil emulsion. The emulsion and CPC compositions can be adjusted in order to control the final features of the microcarriers. The in vitro characterization of the microcarriers reveals that under static and dynamic culturing conditions, microcarrieres are able to support cell attachment, proliferation and differentiation.
