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Study of biocompatibility of nanostructured materials on in vitro and in vivo models

  • Autores: Anna Barbara Orlowska
  • Directores de la Tesis: Vladimir Baulin (dir. tes.)
  • Lectura: En la Universitat Rovira i Virgili ( España ) en 2022
  • Idioma: inglés
  • Número de páginas: 360
  • Tribunal Calificador de la Tesis: Mahvash Tavassoli (presid.), Javier Capilla Luque (secret.), Mohammad Al Kobaisi (voc.)
  • Programa de doctorado: Programa de Doctorado en Nanociencia, Materiales e Ingeniería Química por la Universidad Rovira i Virgili
  • Materias:
  • Enlaces
    • Tesis en acceso abierto en: TDX
  • Resumen
    • English

      Biomaterials play a substantial role in the health care industry. Each year, the number of medical devices used in humans is estimated to be around 1.5 million individual devices, according to the World Health Organization, with about 10 000 types of generic device groups available worldwide. As new devices emerge, the topic of the biocompatibility of these materials becomes more relevant.

      This thesis studies biocompatibility of biomaterials and their interaction with tissues and cells combining in vitro and in vivo models. The studied biomaterials are classified in synthetic (polymers, silicon, titanium and alloys) and nature-derived biomaterials, which in turn, classify in xenogenic, derived from natural materials but foreign for the organism and autologous biomaterials, derived from the tissues of the same organism.

      In the case of synthetic materials, it was shown how different functionalization strategies of surfaces (polystyrene, silicon and titanium) affect mammalian cell response. In particular, protein adsorption to black silicon (BSi), a silicon-based nanostructured surface, was investigated to determine the effect of the nanoscale topography on protein adsorption. Both albumin (Alb) and fibronectin (Fn) adsorb to a greater extent on a smooth surface than on the nanotopography of black silicon, however the adsorption profiles differ between them. At low concentrations (below 40 μg/ml), Alb tends to collect at the bottom of nanopillars, whereas at high concentrations deposition shifts to the top. In contrast, Fn preferentially adsorbed on the top of the nanopillars regardless of the concentration. The effects of protein coating to promote cell attachment and differentiation were also studied using PC12 cells, showing that by controlling the protein coating it is possible to improve cell attachment and differentiation. In vitro and in vivo studies showed BSi is biocompatible while displaying bactericidal properties. Similar surface topography has been applied to titanium, widely used as a biomaterial, showing an improvement of cellular response in regards to the flat one.

      Autologous biomaterials were represented by platelet rich fibrin (PRF). This is a naturally derived hydrogel obtained from the host peripheral blood. Its potential as implantable system was studied in-vitro and in-vivo. Different preparation methods by varying relative centrifugal force and centrifugation time were tested for growth factors storage capacity and release as well as cellular retention within the matrix. Moreover, an in vivo implantation model was employed to evaluate tissue reaction. Comparison of different solid PRF matrixes show that epidermal growth factor (EGF) release was highest in the initial 24 hours while also showing that preparations with lower centrifugation time are able to retain a larger amount of growth factors. Liquid PRF matrixes show an inverse correlation between the centrifugation force and the number of cells, as well as the concentration of growth factors. Furthermore in vivo studies show higher vascularisation rate in PRF preparations in lower centrifugation force. These studies indicate that modification of RCF can be used to acquire, as well as tailor matrices with special characteristic that can be used for specific applications, like guided bone formation or guided tissue regeneration.

      Xenogenic biomaterials were represented by collagen membranes. The goal of this study was to measure cellular permeation into the membrane and its liquid absorption by applying liquid PRF system. Furthermore, an in vivo implantation model was utilized to establish host tissue response, in particular, multinucleated giant cells (MNGCs) formation and their impact on neovascularization. Overall, this study shows that all tested collagen membranes are biocompatible and support cell adhesion and proliferation. Some of the membranes promoted foreign body reaction, described by MNGCs formation and collagen deposition around the materials. Interestingly, together with the gradual increase of a MNGCs within implantation bed over time, an increase in the number of blood vessels was noticed. This leads to the conclusion that moderate presence of MNGCs does not affect biocompatibility of a material in a harmful manner, but on the contrary might have a positive effect on neovascularization of the implant environment. Some of the membranes were also found to be non-permeable to the liquid PRF matrix (fibrin leukocytes and platelets), suggesting that they could be used as a barrier to prevent the ingrowth of undesired cells.

    • English

      Biomaterials play a substantial role in the health care industry. Each year, the number of medical devices used in humans is estimated to be around 1.5 million individual devices, according to the World Health Organization, with about 10 000 types of generic device groups available worldwide. As new devices emerge, the topic of the biocompatibility of these materials becomes more relevant. This thesis studies biocompatibility of biomaterials and their interaction with tissues and cells combining in vitro and in vivo models. The studied biomaterials are classified in synthetic (polymers, silicon, titanium and alloys) and nature-derived biomaterials, which in turn, classify in xenogenic, derived from natural materials but foreign for the organism and autologous biomaterials, derived from the tissues of the same organism. In the case of synthetic materials, it was shown how different functionalization strategies of surfaces (in particular, the effect of protein coating and surface topography) affect mammalian cell response. Autologous biomaterials were represented by platelet rich fibrin (PRF), derived from the blood of the patient. Their potential as implantable system was studied in vitro and in vivo.

    • català

      Els biomaterials tenen un paper important en la indústria de la salut. Cada any, s'estima que el nombre de dispositius mèdics utilitzats en humans és d'uns 1,5 milions de dispositius individuals, segons l'Organització Mundial de la Salut, amb uns 10.000 tipus de grups de dispositius genèrics disponibles a tot el món. A mesura que sorgeixen nous dispositius, el tema de la biocompatibilitat d'aquests materials es torna més rellevant. Aquesta tesi estudia la biocompatibilitat de biomaterials i la seva interacció amb teixits i cèl·lules combinant models in vitro i in vivo. Els biomaterials estudiats es classifiquen en biomaterials sintètics (polímers, silici, titani i aliatges) i biomaterials derivats de la naturalesa, que al seu torn, es classifiquen en xenogènics, derivats de materials naturals però estranys per a l'organisme i biomaterials autòlegs, derivats dels teixits dels mateixos. organisme. En el cas dels materials sintètics, es va demostrar com les diferents estratègies de funcionalització de les superfícies (en particular, l'efecte del recobriment de proteïnes i la topografia superficial) afecten la resposta de les cèl·lules de mamífer. Els biomaterials autòlegs estaven representats per fibrina rica en plaquetes (PRF), derivada de la sang del pacient.


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