Clausthal, Techn. University, Diss., 2005.

Universiẗat, Diss., 2006--Giessen.

Zugl.: Giessen, Univ., Diss., 2006

Tierärztl. Hochsch., Diss., 2003--Hannover.

Universiẗat, Diss., 2007--Giessen.

Universiẗat, Diss., 2006--Giessen.

Universiẗat, Diss., 2001--Gießen.

Gegenstand der vorliegenden Arbeit war die Modifikation von Hydroxylapatit- und Bruschit-Zementen mit 1 % Silber. Ziel war es, den Zementen eine antibakterielle Wirksamkeit bei gleichzeitiger Biokompatibilität ohne Beeinträchtigung ihrer mechanischen Eigenschaften zu verleihen. Durch Mischung von silberdotiertem β-TCP mit Calcium-bis-dihydrogenphosphat Monohydrat (MCPM) bzw. von silberdotiertem α-TCP mit einer 2,5%-Na2HPO4-Lösung entstanden Zementformulierungen, deren Silberfreisetzung, Druckfestigkeit, Abbindezeit sowie Phasenzusammensetzung bestimmt wurde. Desweiteren wurden in vitro-Untersuchungen zur Evaluation der Zytotoxizität mittels Osteoblasten sowie der antibakteriellen Eigenschaften mittels Staph. aureus und Staph. epidermidis durchgeführt. Bei der massenspektrometrischen Analyse der Auslagerungsmedien legte Ag-Bruschit im LB-Medium mit kumulativ 184,5 µg nach 7 Tagen das höchste Freisetzungsverhalten im Vergleich zu Ag-Hydroxylapatit mit 36,8 µg an den Tag; außerdem konnte gezeigt werden, dass sich das molare Verhältnis von Ag+/Ca2+ von theoretisch 1 % bereits bei der Herstellung von Ag+-dotiertem α- bzw. β-TCP auf je 0,78 % reduziert hatte. Die Untersuchung der Phasenzusammensetzung der Zemente wies auf die für die Zemente charakteristischen Beugungsmuster hin. Peaks, die auf Silber hinweisen würden, konnten nicht nachgewiesen werden. Betrachtet man die Druckfestigkeit, konnte der silberdotierte Bruschit-Zement eine leichte Steigerung um 5,1 MPa auf 19,8 MPa erfahren, während der Ag-Hydroxylapatit-Zement nahezu eine Halbierung seiner Festigkeit um 18,5 MPa auf 22,7 MPa erfahren musste. Bei der Auswertung der Versuchsergebnisse wies Ag-Bruschit einen signifikanten bakteriziden Effekt auf, führte aber auch zu einer Reduktion der Osteoblasten auf dieser Oberfläche. Ag-Hydroxylapatit zeigte hingegen nur eine geringe Wirkung gegen die Bakterien, während die Verbindung in dieser in vitro-Studie eher biokompatibel auf die Zellen wirkte. Die in dieser Arbeit modifizierten Zemente sind aufgrund ihrer nicht einheitlichen Ergebnisse hinsichtlich der antibakteriellen Wirksamkeit sowie der wünschenswerten Biokompatibilität für den Einsatz als Knochenersatzmaterial noch nicht geeignet. Die von Ag-Bruschit freigesetzte bakterizide Silbermenge ist für eukaryotische Zellen zu hoch, sodass in weiterführenden Studien diese Freisetzung begrenzt werden müsste. / The present work was the modification of hydroxyapatite and brushite cements with 1% silver. The aim was to give the cement an anti-bacterial activity simultaneously with a biocompatibility without compromising their mechanical properties. Cement formulations, of which the release of silver ions, compressive strength, setting time and phase composition were determined, emerged by mixing silver-doped β-TCP with calcium bis-dihydrogen phosphate monohydrate (MCPM) or by silver-doped α-TCP with a 2.5% Na2HPO4 solution. Furthermore, in vitro- studies were performed to evaluate the cytotoxicity by osteoblasts, and the antibacterial properties using Staph. aureus and Staph. epidermidis. In the mass spectrometric analysis of the outsourcing media, Ag brushite in LB-medium with cumulative 184.5 µg after 7 days, demonstrated the highest release behavior as compared to Ag-hydroxyapatite with 36.8 µg; it also could be shown that the molar ratio of Ag+/ Ca2+ of theoretically 1% had already reduced to 0.78% in the production of Ag+-doped α- and β-TCP. The investigation of the phase composition of the cements showed the characteristic diffraction pattern for these cements. Peaks, which would indicate silver, could not be detected. Considering the compressive strength, the silver-doped brushite cement had shown a slight increase of 5.1 MPa to 19.8 MPa, while the Ag-hydroxyapatite cement had experienced a near halving of its strength of 18.5 MPa to 22.7 MPa. When evaluating the test results, Ag-brushite presented a significant bactericidal effect, but also led to a reduction of osteoblasts on the surface. Ag-hydroxyapatite offered a little effect against the bacteria, while the compound in this in vitro- study had more biocompatible to the cells. The modified cements in this study are, due to their non-uniform results in terms of antibacterial efficacy as well as the desirable biocompatibility, not suitable for the use as a bone substitute material. The release of Ag-brushite bactericidal amount of silver for eukaryotic cells is too high, so this release should be limited in further studies.

Techn. Hochsch., Diss., 2002--Aachen.

Abstract Objective Cranioplasty is routinely performed in neurosurgery. One of its underestimated problems is the high postoperative complication rate of up to 40%. Due to the lack of good prospective studies and the low number of patients (5–20 each year) receiving alloplastic materials, decisions in favor or against a certain material are based on subjective empirical or eco-nomic reasons. The main goal of this first prospective, randomized multicenter study in Germany of custom-made titanium and hydroxyapatite (HA) implants was to compare lo-cal and systemic infections related to the implant within the first six months after implanta-tion. Secondary objectives included comparing reoperation rates, the complication rate, clinical and neurological outcome, and health-related quality of life. Methods The study included patient screening and randomization 6–8 weeks before operation, pre-, intra and postoperative documentation until discharge, and postoperative follow-ups after one and six months. Approval for the study was obtained from the local ethics committee. The study design was published on www.clinicaltrials.gov. Results A total of 52 patients were included in the study. The rate of local, implant associated wound infection in the HA group was 2 out of 26 (7.7%) patients and 5 out of 24 (20.8%) patients in the titanium group (p=0.407 n.s.). Systemic inflammation within six months after operation affected none of the patients in the HA group and 4 out of 24 (37.5%) pa-tients in the titanium group (p=0.107 n.s.). In both groups, 7 patients had to be reoperated after the six-month follow-up (26.9% in the HA group and 29.2% in the titanium group; n.s.). Re-surgery with explantation was necessary in 3 patients in each group (11.5% in the HA group and 12.5% in the titanium group; n.s.). The results demonstrated a significantly higher number of epidural hematomas in the HA group compared to none in the titanium group. Altogether, 46 AE were measured in 27 patients (54%). An improvement of the neurologi-cal outcome after six months was experienced by 43% of the patients in the HA group and 26.3% in the titanium group (p=0.709 n.s.). Conclusion The study emphasizes that cranioplasty is a high-risk intervention. Compared to tita-nium, HA shows a benefit in the infection rate and the neurological outcome, but has at the same time a higher postoperative risk for epidural hematoma. Depending on the individual conditions both materials have their place in future therapy of cranioplasty.