Papers by Christine Knabe
Clinical Oral Implants Research, 2004
Using biodegradable bone substitutes in alveolar ridge augmentation avoids second-site surgery fo... more Using biodegradable bone substitutes in alveolar ridge augmentation avoids second-site surgery for autograft harvesting. Considerable efforts have been undertaken to develop rapidly resorbable bone substitute materials with a higher degree of biodegradability than tricalcium phosphate (TCP). This study examines the effect of novel biodegradable glass ceramics on the expression of bone-related genes and proteins by human bone-derived cells (HBDC) and compares this behavior with that of TCP. Test materials used were alpha-TCP, a surface-treated glass ceramic GB9N with crystalline phase Ca(2)KNa(PO(4))(2) and a small amount of amorphous silica phosphate; AP40 - a glass ceramic based on crystalline phases of apatite and wollastonite; and a glass ceramic Mg5 composed of 20.6% CaO, 58.5% P(2)O(5), 14.4% Na(2)O, 4.1% MgO and 2.4% CaF(2) (wt%). HBDC were grown on the substrata for 3, 5, 7, 14 and 21 days, counted and probed for various bone-related mRNAs and proteins (type I collagen (Col I), osteocalcin (OC), osteopontin (OP), osteonectin (ON), alkaline phosphatase (ALP) and bone sialoprotein (BSP)). The substrata supported continuous cellular growth for 21 days. By day 21, GB9N had the highest number of HBDC. GB9N induced significantly enhanced expression of Col I, ALP, OP, OC and ON mRNA at 3 days; of OP, OC and ON mRNA and protein at 7 and 14 days; and of ALP, OP and OC mRNA and Col I, ALP, BSP, ON and OP protein at 21 days. Since all novel glass ceramics supported cellular proliferation together with expression of bone-related genes and proteins at least as much as TCP, these ceramics can be regarded as potential bone substitutes. GB9N had the most effect on osteoblastic differentiation, thus suggesting that this material may possess a higher potency to enhance osteogenesis than TCP.
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International Journal of Urology, 2015
To develop an economic, practical and readily available animal model for preclinical testing of u... more To develop an economic, practical and readily available animal model for preclinical testing of urethral bulking therapies, as well as to establish feasible experimental methods that allow for complete analysis of hard microparticle bulking agents. Alumina ceramic beads suspended in hyaluronic acid were injected into the proximal urethra of 15 female rats under an operating microscope. We assessed overall lower urinary tract function, bulking material intraurethral integrity and local host tissue response over time. Microphotographs were taken during injection and again 6 months postoperatively, before urethral harvest. Urinary flow rate and voiding frequency were assessed before and after injection. At 6 months, the urethra was removed and embedded in resin. Hard tissue sections were cut using a sawing microtome, and processed for histological analysis using scanning electron microscopy, light microscopy and immunohistochemistry. Microphotographs of the urethra showed complete volume retention of the bulking agent at 6 months. There was no significant difference between average urinary frequency and mean urinary flow rate at 1 and 3 months postinjection as compared with baseline. Scanning electron microscopy proved suitable for evaluation of microparticle size and integrity, as well as local tissue remodeling. Light microscopy and immunohistochemistry allowed for evaluation of an inflammatory host tissue reaction to the bulking agent. The microsurgical injection technique, in vivo physiology and novel hard tissue processing for histology, described in the present study, will allow for future comprehensive preclinical testing of urethral bulking therapy agents containing microparticles made of a hard material.
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Key Engineering Materials, Jan 6, 2015
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Key Engineering Materials, 2007
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Biomaterials, 2015
Risk of infection is considerable in open fractures, especially when fracture fixation devices ar... more Risk of infection is considerable in open fractures, especially when fracture fixation devices are used to stabilize the fractured bones. Overall deep infection rates of 16.2% have been reported. The infection rate is even greater, up to 32.2%, with external fixation of femoral fractures. The use of percutaneous implants for certain clinical applications, such as percutaneous implants for external fracture fixation, still represents a challenge today. Currently, bone infections are very difficult to treat. Very potent antibiotics are needed, which creates the risk of irreversible damage to other organs, when the antibiotics are administered systemically. As such, controlled, local release is being pursued, but no such treatments are in clinical use. Herein, the use of bactericidal micron-thin sol-gel films on metallic fracture fixation pins is reported. The data demonstrates that triclosan (2,4,4'-trichloro-2'-hydroxydiphenylether), an antimicrobial agent, can be successfull...
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Key Engineering Materials, 2003
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Key Engineering Materials, 2008
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Developments in X-Ray Tomography VII, 2010
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Military Medicine, 2014
Orthopedic injuries constitute the majority of wounds sustained by U.S. soldiers in recent confli... more Orthopedic injuries constitute the majority of wounds sustained by U.S. soldiers in recent conflicts. The risk of infection is considerable with fracture fixation devices. In this pilot study, we examined the use of unique bactericidal micron-thin sol-gel films on fracture fixation devices and their ability to prevent and eradicate infections. External fixation was studied with micron-thin sol-gel coated percutaneous pins releasing triclosan and inserted medially into rabbit tibiae. A total of 11 rabbits received percutaneous pins that were either uncoated or sol-gel/triclosan coated. Internal fracture fixation was also studied using sol-gel coated intramedullary (IM) nails releasing vancomycin in the intramedullary tibiae. Six sheep received IM nails that were coated with a sol-gel film that either contained vancomycin or did not contain vancomycin. All animals were challenged with Staphylococcus aureus around the implant. Animals were euthanized at 1 month postoperative. Rabbits receiving triclosan/sol-gel coated percutaneous pins did not show signs of infection. Uncoated percutaneous pins had a significantly higher infection rate. In the sheep study, there were no radiographic signs of osteomyelitis with vancomycin/sol-gel coated IM nails, in contrast to the observations in the control cohort. Hence, the nanostructured sol-gel controlled release technology offers the promise of a reliable and continuous delivery system of bactericidals from orthopedic devices to prevent and treat infection.
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Key Engineering Materials, 2014
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Comprehensive Biomaterials, 2011
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Key Engineering Materials, 2011
ABSTRACT The thrust of the investigations presented here is to point out the degradation behaviou... more ABSTRACT The thrust of the investigations presented here is to point out the degradation behaviour in vitro and the ingrowth behaviour in vivo of four different calcium alkaline phosphate cements. Two of the figuline and mouldable composites consist of the crystalline phase Ca2KNa(PO4)2 and two of the crystalline phase Ca10[K/Na](PO4)2 each containing 2wt% medium gel strength porcine gelatin. Furthermore Α-TCP was added to both Ca10[K/Na](PO4)2 cements as a hardening supporting reactant. The testing material groups differ in small amorphous portions containing either silica phosphate (GB9), magnesium potassium phosphate (GB14) or diphosphates (401545 and 401545(70)). The respective composites show a monomodal particle size distribution (d50~7µm; span~4) and an average total porosity around 28vol%.For the solubility studies cylindrical samples (d=6mm; h=12mm) were stored in a 0.1mol TRIS buffer solution and incubated at 37°C for maximum 50 weeks. The storage solution was analysed and renewed every week. The results are plotted cumulative. For the in vivo studies critical size defects were dissected to mandibles in a sheep model in which a 1cm3 area of the bottom of the mandibles was surgically resected and replaced with the figuline cements whereas the mouldability allows the reconstruction of the original outer contour without draining off even when replacing upside down.
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Key Engineering Materials, 2014
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Key Engineering Materials, 2003
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Materialwissenschaft und Werkstofftechnik, 2010
ABSTRACT In this study, two novel bioactive bone-bonding cements based on the crystalline phase C... more ABSTRACT In this study, two novel bioactive bone-bonding cements based on the crystalline phase Ca2KNa(PO4)2 were studied in vivo in order to characterize their bone regenerative capacities as well as their biodegradability. The implantation site was located underneath the patellar sliding plane of the distal femur of rabbits in an area which is almost free of bony trabeculae. Highly porous β-TCP granules and empty defects served as controls. In order to obtain information especially regarding the remodeling properties time periods of up to 48 weeks were chosen. When used as bulk material, both cements showed bone formation rates which were comparable to those of the TCP granules in combination with a favorable biodegradability, which however was lower than that of TCP granules due to the considerably lower porosity. Taken together, a guided bone regeneration in conjunction with biomaterials degradation was observed with all three materials. The empty defects (negative control) did not show comparable bone formation rates. Based on this study, both cements can be considered as valuable materials for percutaneous treatment of bone defects in traumatology, for example. Zwei neue bioaktive knochenbindende Zemente wurden in einem Tiermodel getestet. Die kristalline Hauptphase war Ca2KNa(PO4)2. Untersucht werden sollten die Knochenregeneration und Degradation. Die Materialien wurden hinter dem Patellagleitlager von Kaninchen implantiert. Hier besteht ein Areal, was physiologischer Weise arm an Knochentrabekeln ist. Als Kontrollen dienten ein TCP-Granulat und Leerdefekte. Um Informationen besonders über den Remodelingprozess zu erhalten, wurden Zeitpunkte von bis zu 48 Wochen gewählt. Beide Zemente füllten die Defekte vollständig. Sie zeigten vergleichbare Raten der Knochenneubildung wie TCP-Partikel, wobei die Degradation geringer bzw. langsamer als die der TCP Partikel war aufgrund der geringeren Porosität der Zemente. Die Degradation erreichte nach 48 Wochen jedoch fast den gesamten Defekt, so dass bei gleichzeitiger Knochenbildung von einer gerichteten Knochenregeneration im Defekt gesprochen werden kann. Leerdefekte blieben ohne wesentliche Knochenneubildung. Beide Zemente stellen daher geeignete Materialien zur perkutanen Auffüllung z.B. in der unfallchirurgischen operativen Praxis dar.
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Journal of Cranio-Maxillofacial Surgery, 2005
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Journal of Biomedical Materials Research, 2004
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Journal of Biomedical Materials Research, 2002
Poor cell adhesion to orthopaedic and dental implants may result in implant failure. Cellular adh... more Poor cell adhesion to orthopaedic and dental implants may result in implant failure. Cellular adhesion to biomaterial surfaces primarily is mediated by integrins, which act as signal transduction and adhesion proteins. Because integrin function depends on divalent cations, we investigated the effect of magnesium ions modified bioceramic substrata (Al(2)O(3)-Mg(2+)) on human bone-derived cell (HBDC) adhesion, integrin expression, and activation of intracellular signalling molecules. Immunohistochemistry, flow cytometry, cell adhesion, cell adhesion blocking, and Western blotting assays were used. Our findings demonstrated that adhesion of HBDC to Al(2)O(3)-Mg(2+) was increased compared to on the Mg(2+)-free Al(2)O(3). Furthermore, HBDC adhesion decreased significantly when the fibronectin receptor alpha5beta1- and beta1-integrins were blocked by functional blocking antibodies. HBDC grown on the Mg(2+)-modified bioceramic expressed significantly enhanced levels of beta1-, alpha5beta1-, and alpha3beta1-integrins receptors compared to those grown on the native unmodified Al(2)O(3). Tyrosine phosphorylation of intracellular integrin-dependent signalling proteins as well as the expression of key signalling protein Shc isoforms (p46, p52, p66), focal adhesion kinase, and extracellular matrix protein collagen type I were significantly enhanced when HBDC were grown on Al(2)O(3)-Mg(2+) compared to the native Al(2)O(3). We conclude that cell adhesion to biomaterial surfaces is probably mediated by alpha5beta1- and beta1-integrin. Cation-promoted cell adhesion depends on 5beta1- and beta1-integrins associated signal transduction pathways involving the key signalling protein Shc and results also in enhanced gene expression of extracellular matrix proteins. Therefore, Mg(2+) supplementation of bioceramic substrata may be a promising way to improve integration of implants in orthopaedic and dental surgery.
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Journal of Biomedical Materials Research, 2004
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Papers by Christine Knabe