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Authors: Schröder, Romina
Title: Vaterit als Biomaterial - Relevanz für die natürliche Knochenregeneration und die Apatit-Synthese
Online publication date: 19-Jan-2021
Language: german
Abstract: The present work investigates a promising alternative to conventional synthetic biomaterials for regeneration of small bone defects or bone diseases (e.g. osteoporosis). The studies were carried out on the least stable calcium carbonate polymorph vaterite. The aim of this thesis was to assess the biological and chemical properties of synthetically produced vaterite particles as a biomaterial for natural bone formation and thus for a potential application in bone regeneration.The first chapter of the thesis describes a simple and fast synthesis of sterile vaterite particles resulting in a nearly quantitative yield. The particles were obtained as phase-pure vaterite and showed an ellipsoidal shape with a diameter of 0.5 – 1.0 μm. In addition, extensive in vitro studies were performed with human cells, showing that the synthesized vaterite particles (i) did not exhibit any cytotoxic effects on the human cells (detection by MTS, LDH and crystal violet assay), (ii) were free of endotoxins, (iii) did not induce an inflammatory response in human endothelial cells, (iv) showed superior cell biocompatibility with primary human osteoblasts and endothelial cells and (v) stimulated the differentiation of osteoblasts (demonstrated by activity of the alkaline phosphatase).This thesis focusses on the study of the transformation of synthesized vaterite particles to a bonelike hydroxy apatite (HA). The second chapter deals with the incubation of vaterite particles in phosphate containing solutions (simulated body fluid, phosphate buffered saline and cell culture medium) at physiological pH and 37 °C up to 6 months. The transformation of vaterite to a HA species was quantified by using a combination of powder X-ray diffraction (XRD) and spectroscopic methods (FT-IR, 31P solid state NMR) and supplemented by microscopic methods (SEM, TEM). Based on these results, a direct synthesis of HA particles from vaterite particles is described in the third chapter. The reaction was controlled by potentiometric measurements and initial in vitro cell tests were performed. The following interesting and advantageous properties of the resulting HA species were determined. (i) Targeted and controllable crystallization of the HA species by in situ release of Ca2+ ions, (ii) formation of a specific HA species including foreign ions adapted to the reaction medium, (iii) HA crystallites with similar morphology and size to the biological HA crystallites, (iv) very good cell biocompatibility with human osteoblasts and (v) a physiological differentiation of osteoblasts occurred. In the final fourth chapter a hydrogel-based scaffold for a targeted and localized application of the vaterite particles is discussed. In contrast to free vaterite particles the transformation in a chemically and biologically inert PEG-based hydrogel scaffold proceeded significantly faster. Furthermore, the previously determined biological properties of vaterite particles were also detected in vitro within the hydrogel scaffold. It was shown that a combination of inorganic vaterite particles with an organic hydrogel scaffold is beneficial for use in bone regeneration application since (i) a targeted and individually adapted structure of a natural bone mineral occurred by the vaterite particles, (ii) no additional compounds promoting bone formation are necessary due to the osteoconduvtive and osteoinduktive effects of vaterite particles and (iii) in the long-term a natural bone regeneration without a foreign body should occur. In vivo, the vaterite particles should transform to a natural bone mineral and by using a degradable hydrogel scaffold no foreign components would remain in the body.
DDC: 540 Chemie
540 Chemistry and allied sciences
Institution: Johannes Gutenberg-Universität Mainz
Department: FB 09 Chemie, Pharmazie u. Geowissensch.
Place: Mainz
Version: Original work
Publication type: Dissertation
License: CC-BY-ND
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Extent: VIII, 252 Seiten
Appears in collections:JGU-Publikationen

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