Tuning the biological performance of calcium phosphates through microstructural and chemical modifications
Bone is the most transplanted tissue after blood. As pointed out by the World Health Organization, musculoskeletal diseases can potentially rise as the fourth largest cause of disability within the next years. Unfortunately, despite the natural ability of bone to self-heal it cannot bridge large bon...
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| Tipo de recurso: | tesis doctoral |
| Estado: | Versión publicada |
| Fecha de publicación: | 2017 |
| País: | España |
| Institución: | CBUC, CESCA |
| Repositorio: | TDR. Tesis Doctorales en Red |
| OAI Identifier: | oai:www.tdx.cat:10803/620730 |
| Acceso en línea: | http://hdl.handle.net/10803/620730 https://dx.doi.org/10.5821/dissertation-2117-121021 |
| Access Level: | acceso abierto |
| Palabra clave: | Àrees temàtiques de la UPC::Enginyeria dels materials 615 616.7 620 |
| Sumario: | Bone is the most transplanted tissue after blood. As pointed out by the World Health Organization, musculoskeletal diseases can potentially rise as the fourth largest cause of disability within the next years. Unfortunately, despite the natural ability of bone to self-heal it cannot bridge large bone defects without the help of a material. Still today the gold standard to restore bone function remains the use of natural bone grafts. However, they have several limitations that need to be overcome to accommodate the high demands of a global ageing population. Calcium phosphate (CaP) bone grafts have been known since the 1970s and stand as excellent synthetic candidates due to their composition, similar to the mineral phase of bone which consists of approximately 70 wt% of hydroxyapatite (HA). CaPs, and in particular HA, possess outstanding intrinsic properties such as biocompatibility, bioactivity and the ability to support bone growth. However, HA is too stable and once implanted it hardly degrades. Ideal synthetic bone grafts should integrate in the bone remodelling cycle, balancing implant resorption with its progressive replacement by new bone. This can be achieved either by modulating the material¿s physicochemical properties, or by combining the substrate with biological molecules capable of adequately orchestrating the various cells involved in the bone healing process. The present thesis seeks to explore, on the one hand, the feasibility of modulating the physicochemical properties of CaPs towards improving its degradation behavior, and, on the other hand, to investigate the potential CaP functionalization with heparin as a strategy to improve their biological performance at the various stages of bone healing: during the initial phase of inflammation, and during the stages of bone resorption and bone growth. The first part of the present thesis deals with the in vitro degradation of CaPs in a solution mimicking the osteoclastic environment, focusing specifically on the effect of some properties like porosity, specific surface area, microstructure and composition. The interrelation of all these parameters sometimes masks the relative importance of textural over compositional features, making difficult the prediction of their degradation behavior. Additionally, part of the work explores different strategies to incorporate carbonate ions in the crystal structure of HA as a route to obtain materials that more closely mimic natural bone. To further mimic the biological environment of bone, the second part of the thesis is focused on grafting heparin, a highly sulfated glycosaminoglycan present in the bone extracellular matrix, to CaPs. The affinity of heparin for growth factors (GF) makes this molecule an excellent candidate to capture endogenous GF bringing many benefits in the regulation of cell behavior. It is hypothesized that heparin, given its anti-inflammatory role, together with the known involvement in osteoblasts differentiation (bone forming cells) and osteoclastogenesis (bone resorbing cells formation) could enhance the biological performance of synthetic bone grafts. To this aim, CaPs were heparinized and their biological performance was assessed using human immune system cells, bone forming cells and bone resorbing cells, in an attempt to elucidate the synergies of both immune cells and cells of the skeletal system. |
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