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The biological and physical performance of high strength dicalcium phosphate cement in physiologically relevant modelsPujari-Palmer, Michael January 2017 (has links)
The chemical properties of calcium phosphate cements (CPCs) are very similar to the mineral phase of bone. CPCs are, consequently, very effective substrates (scaffolds) for tissue engineering; bone and stem cells attach readily, and can proliferate and differentiate to form new bone tissue. Unlike other CPCs that may remain largely unchanged in the body for years, such as hydroxyapatite, dicalcium phosphates are remodelled by the body and rapidly converted to new bone. Unfortunately, the dicalcium phosphates are also typically too weak to support load bearing in the human body. Our laboratory has recently developed a novel, high strength brushite CPC, (hsCPC), which can reach 10-50 fold higher failure strength than many commercially available CPCs. The aim of this thesis was to investigate the physical, chemical and biological performance of hsCPCs in physiologically relevant model of drug release, load bearing, osteoconductivity, and as a scaffold for bone tissue engineering. Multiple CPCs were compared in a model of screw augmentation to determine whether the physical properties of the cement, such as bulk strength and porosity, affected orthopedic screw holding strength. In an in vitro model of bone regeneration stem cells were grown on macroporous scaffolds that were fabricated from hsCPC. Drug releasing scaffolds were fabricated to examine whether the low porosity of hsCPC impeded drug release during a 4 week incubation period. The biological activity of an incorporated drug, Rebamipide, was examined after acute and chronic incubation periods. In the drug release study it was noted that the biological response to hsCPC was significantly better than tissue culture grade polystyrene, even in groups without drug. The mechanism underlying this biological response was further investigated by testing the effect of pyrophosphate, a common cement additive, on bone cell proliferation and differentiation. This thesis concludes that a high strength cement can produce significant improvement in screw augmentation strength, if there is sufficient cortical bone near the augmentation site. The hsCPC is also cytocompatible, and can support bone and stem cell proliferation and differentiation. hsCPC scaffolds stimulated osteogenic gene expression comparable to native bone scaffolds. hsCPC scaffolds are also capable of delivering drug for up to 4 weeks, in vitro. Finally, a cement additive, pyrophosphate, stimulated differentiation, but not proliferation of bone cells.
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Validierung des Knochenumbaus von Knochenersatzmaterialien in der Mund-, Kiefer- und GesichtschirurgieSoost, Frank 06 March 2001 (has links)
Die Behandlung entzündlicher, tumorbedingter, dysmorphischer oder posttraumatischer Defekte des menschlichen Skeletts hat besonders in den letzten drei Jahrzehnten neben dem Standard der Behandlung, der Übertragung von körpereigenen Hartgeweben und in konserviertem Zustand übertragenem Spendermaterial, auch Knochenersatzmittel in der Therapie etabliert und in Qualität und Quantität der Eingriffe an Bedeutung gewonnen. Die Diskussion über die Übertragbarkeit von Infektionskrankheiten durch Gewebe aus Knochenbanken hat den Einsatz von konserviertem Spenderknochen in den Hintergrund treten lassen. Aus diesem Grunde wird immer wieder nach geeigneten Knochenersatzmaterialien gesucht. Zahlreiche Implantate aus verschiedenen physikalisch und chemisch differenten Stoffgruppen wurden auf ihre Eignung zum Knochenersatz getestet. Ein ideales Material wurde bislang nicht gefunden. Im Tierversuchsmodell und in der klinischen Anwendung beim Menschen wurden verschiedene Knochenersatzmaterialien hinsichtlich der Dynamik der Knochenumbauprozesse mittels nuklearmedizinscher und röntgenologischer Verfahren evaluiert und im Ergebnis des knöchernen Substitues histologisch bezüglich ihrer Wertigkeit für den funktionellen Knochenersatz untersucht. Im Vergleich zum autogenen Knochentransplantat entstanden im Ergebnis der Implantation osteoinduktiver und osteokonduktiv wirkender Knochenersatzmaterialien Substitute, die ausnahmslos und vor allem bei den keramischen Implantaten als unvollständige Restitution zu werten waren. / Alongside the standard donor bone transfer, bone substitutes have established themselves, improved in quality and are being increasingly used in the surgical treatment of dysmorphic defects or defects following inflammation, tumor surgery or trauma, particularly in the last three decades. With the discussion about infectious disease transmission through tissue from bone banks, the use of donor bone has receded into the background. For this reason, suitable bone substitutes are being sought constantly. Implants of many different physical and chemical substance groups have been tested for their suitability as bone substitutes, but an ideal material has yet to be found. In animal experiment models and their clinical application in humans, various bone substitutes have been evaluated for the dynamic of the resulting bone formation using nuclear medical and radiological procedures and have been examined histologically for their value as functional bone substitutes. Compared to autogenous bone grafts, the bone substitutes which have emerged as the result of the implantation of osteoinductive and osteoconductive materials have, without exception and particularly in the case the ceramic implants, shown incomplete restitution.
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Histomorphometrische Evaluation der Knochenneubildung mit Hilfe eines osteoinduktiven Faktors bei der Sinusbodenaugmentation im Göttinger Minipig / Histomorphometric evaluation of new bone formation using an osteoinductive factor during sinus floor augmentation in Goettingen minipigsBrockmeyer, Phillipp 04 December 2013 (has links)
No description available.
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Reduced Burst Release of Bioactive rhBMP-2 from a Three-phase Composite ScaffoldGrant, David William 31 December 2010 (has links)
Recombinant human bone morphogenic proteins (rhBMPs) are extensively studied and employed clinically for treatment of various bone defects. Current clinical delivery vehicles suffer wasteful burst releases that mandate supra-physiological dosing driving concerns over safety and cost. It was therefore investigated whether a unique drug delivery vehicle sequestered within a composite scaffold could lower the burst release of rhBMP-2. PLGA-calcium phosphate tri-phasic composite scaffolds delivered model protein BSA with burst release of ~13% and sustained kinetics of 0.5-1.5% BSA/day up to 45 days. rhBMP-2 was delivered with zero burst release however at much lower levels, totaling 0.09% to 0.9 % release over 10 days, but had up to 6.3-fold greater bioactivity than fresh rhBMP-2 (p<0.05). In conclusion, the three-phase composite scaffold can deliver bioactive proteins with a reduced burst release and sustained secondary kinetics.
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Reduced Burst Release of Bioactive rhBMP-2 from a Three-phase Composite ScaffoldGrant, David William 31 December 2010 (has links)
Recombinant human bone morphogenic proteins (rhBMPs) are extensively studied and employed clinically for treatment of various bone defects. Current clinical delivery vehicles suffer wasteful burst releases that mandate supra-physiological dosing driving concerns over safety and cost. It was therefore investigated whether a unique drug delivery vehicle sequestered within a composite scaffold could lower the burst release of rhBMP-2. PLGA-calcium phosphate tri-phasic composite scaffolds delivered model protein BSA with burst release of ~13% and sustained kinetics of 0.5-1.5% BSA/day up to 45 days. rhBMP-2 was delivered with zero burst release however at much lower levels, totaling 0.09% to 0.9 % release over 10 days, but had up to 6.3-fold greater bioactivity than fresh rhBMP-2 (p<0.05). In conclusion, the three-phase composite scaffold can deliver bioactive proteins with a reduced burst release and sustained secondary kinetics.
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