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Titel: Bone regeneration by tuning the drug release from the calcium phosphate scaffolds
Verfasser: Khurana, Kanupriya
Sprache: Englisch
Erscheinungsjahr: 2017
DDC-Sachgruppe: 570 Biowissenschaften, Biologie
Dokumentart : Dissertation
Kurzfassung: Bone is among the most transplanted tissues with more than a million surgical procedures annually in Europe, and around two million worldwide. The regeneration of bone defects, caused by trauma, congenital deformities, age-related bone loss or bone infections represents an urgent challenge for today’s healthcare system. This has fueled the demand of more efficient synthetic bone substitutes. Due to their similar characteristics to the mineral phase of bone, calcium phosphates (CaPs) have raised a lot of interest. Some properties of calcium phosphates, like biodegradability, biocompatibility, bioactivity and osteoconduction represent a great potential for this application. Among them, calcium phosphate cements (CPCs) have additional advantages like injectability and insitu hardening ability. Moreover, the possibility to tune the porosity of CaPs in general and of CPCs in particularmakes them suitablevehicles for local delivery of drugs. Loading CaPs with drugs allows conferring additional functionalities to the synthetic bone grafts, which is of great interest. The main aim of this thesis is to explore CaP bioceramics as vehicles for local delivery of drugs, covering both low temperature biomimetic ceramics, like calcium deficient hydroxyapatite (CDHA), and high temperature sintered ceramics, like beta tricalcium phosphate (β-TCP), in the form of microporous and macroporous substrates. The physic-chemical nature of these bioceramics, their porosity and textural properties plays an essential role in their drug delivery properties. In order to be able to tailor the drug release kinetics of the bioceramics beyond their intrinsic properties, plasma polymerization has been investigated. Plasma is a particular state of a gas, electrically neutral, which is formed by ions, electrons, radicals, metastables, UV and visible radiation and can be employed in different applications. Although plasma polymerization has been widely studied for biomedical applications, its combination with bioceramics is rather unexplored. To select a suitabledrug for bone regeneration, an extensive literature review was done on statins, and more particularly on simvastatin as a potential osteogenic and angiogenic promoter (Chapter 2). This drug was evaluated within macroporous scaffolds of either CDHA or β-TCP as drug delivery vehicles. The drug-loaded materials were plasma-coated with polycaprolactone:poly ethylene glycol (PCL:PEG) co-polymers. The coating covered xvithe micro and nanopores of the CaPs surface and produced complex geometries presenting a nano and micro rough morphology which led to low wettability despite the hydrophilicity of the copolymer. Plasma coating with PCL-co-PEG on scaffolds loaded with simvastatin acid allowed delaying and modulating the drug release from the bone scaffolds depending on the thickness of the layer deposited, which, in turn depended on the initial specific surface area of the CaP (Chapter 3).To further investigate the fundamentals of plasma polymerization on bioceramics, PEG-like polymer coatings of different thickness were deposited on microporous β-TCP loaded with antibiotics. The rough β-TCP surface was associated to strong hydrophobic surface properties, which nevertheless retained their suitablebiological behavior with regard to human osteoblast cells. The microbiological activity of the antibiotics was preserved, and the coatings reduced the total amount of drug released as a function of the increasing plasma treatment time (Chapter 4). In another approach, a statin that had never before been employed in combination withCaPs, Pitavastatin (PITA), was investigated as potentially osteogenic and angiogenic promoter through in vitro studies which revealed dose-dependent enhancement of mineralization and vascularization. The incorporation of PITA to the liquid phase of an injectableCDHA foam allowed obtaining injectablelocal drug delivery scaffolds, without altering their macroporosity or textural properties. The drug release kinetics was affected by the evolving microstructure of the setting of the macroporous cement. Overall the results obtained proved that PITA seems to be a suitablenovel candidate to enhance the osteogenic potential of synthetic bone grafts and identified the required doses to obtain the desired biological effects (Chapter 5).
Knochen gehört zu den am meisten transplantierten Geweben mit mehr als einer Million chirurgischen Verfahren jährlich in Europa und rund zwei Millionen weltweit. Die Regeneration von Knochenfehlern verursacht durch Trauma, angeborene Deformitäten, altersbedingter Knochenverlust oder Knocheninfektionen, stellt eine dringende Herausforderung für das heutige Gesundheitssystem dar. Aufgrund ihrer ähnlichen Eigenschaften zu der Mineralphase des Knochens haben Calciumphosphate (CaPs) ein großes Potenzial für diese Anwendung. Unter ihnen haben Calciumphosphat-Zemente (CPCs) zusätzliche Vorteile wie Injektionsfähigkeit und in situ Härtungsfähigkeit. Darüber hinaus erlaubt die Steuerung der Porosität, CaPs als geeignete Träger für die lokale Wirkstoffabgabe zu nutzen. Das Laden von CaPs mit Medikamenten erlaubt es, den synthetischen Knochentransplantaten zusätzliche Funktionalitäten zu verleihen. Das Hauptziel dieser Arbeit ist es, CaP-Biokeramiken als Träger für die lokale Wirkstoffabgabe zu erforschen. Biomimetisch Tieftemperatur-Keramiken wie Kalzium-defiziente Hydroxyapatite (CDHA) und hochtemperaturgesinterte Keramiken wie Beta-Tricalciumphosphat (β-TCP) in Form von mikroporösen und makroporösen Substraten werden untersucht. Pitavastatin (PITA) wurde als potentiell osteogener und angiogenetischer Promotor eingesetzt. Um die Kinetik der Wirkstoffabgabe der Biokeramiken anzupassen, wurde die Plasmapolymerisation untersucht.
Link zu diesem Datensatz: urn:nbn:de:bsz:291-scidok-ds-273810
hdl:20.500.11880/27214
http://dx.doi.org/10.22028/D291-27381
Erstgutachter: Mücklich, Frank
Tag der mündlichen Prüfung: 10-Nov-2017
SciDok-Publikation: 14-Nov-2018
Fakultät: NT - Naturwissenschaftlich- Technische Fakultät
Fachrichtung: NT - Materialwissenschaft und Werkstofftechnik
Fakultät / Institution:NT - Naturwissenschaftlich- Technische Fakultät

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