In-vivo Quantifikation der Gentamicinfreisetzung aus einer Implantatbeschichtung im Rattenmodell

Beschreibung

"In-vivo quantification of gentamicin released from an implant coating" The intramedullary osteosynthesis of the tibia with a mark nail is a frequently used method for the stabilization of fractures in accident surgery. However, any material implanted in the body presents an increased risk of bacterial surface colonization (Gristina et al., 1988). This promotes the development of deep wound infections (Jansen & Peters, 1993). Implantassociated infections are still one of the most serious complications in fracture care. Using a biodegradable implant coating, active substances can be incorporated into a polymer carrier material for controlled release (Wildemann et al., 2004). The implant can thus function as a so called "drug delivery system" (Fuchs et al., 2011). By means of these systems, a local antimicrobial effect in the fracture area can be achieved, thus reducing the risk of bacterial colonization (Lucke et al., 2003). In addition, adverse drug effects of a systemic drug administration can be limited by using a local antibiotic therapy. The present work comprises detailed in-vitro and in-vivo analysis of the drug release and enrichment of the antibiotic agent gentamicin incorporated into the polymer coating poly(D, L- lactide). In the in-vivo study, gentamicin coated titanium wires were implanted in the tibiae of rats and removed at various time points for a period up to 42 days post implantation. For investigation of the in-vivo release kinetics, the gentamicin concentration was quantified on the explanted wires, in the bone, in the endosteum, in the kidney and in the serum of the rats. Furthermore, radiographic, histological and immunohistological analyses were performed, enabling to gain further information about the distribution and accumulation of gentamicin in the above mentioned tissues. The release kinetics of the locally administered antimicrobial agent gentamicin in the in-vitro and in-vivo studies were comparable. In-vitro as well as in-vivo, an initial increase in the release of gentamicin could be observed. The highest gentamicin concentrations could be measured at the time point "one hour" after implantation of the titanium wires in all analysed tissues and on the titanium wires. During the entire period from one hour to 42 days post implantation, the agent gentamicin could be detected in the endosteum. At the time point "four hours" after implantation of the titanium wires, an antimicrobial effective gentamicin concentration could be detected. No signs of destructive alterations in the bone tissue due to the implant or its coating could be observed by means of radiological investigation of the tibia, indicating a good bio-integrity of implant and polymer coating. Immunohistochemical staining using the avidin- biotin complex method revealed an accumulation of gentamicin in the area of the renal cortex, presumably due to the renal elimination of the drug. The histological investigation of the kidney tissue, performed to exclude a toxic effect of the released gentamicin, did not show any signs of inflammatory or necrotic processes. Since the renal excretion rate has not been determined in the present work, the absolute amount of the invivo released gentamicin could not be calculated. The combination of the different methods for the quantification and visualization of gentamicin in the tissues used in this work, allows to gain information about the accumulation and the activity of the locally released antimicrobial agent during the entire study period. Due to the risk of bacterial infection in open tibia fractures and following fracture stabilization, a local antibiotic activity as soon as possible is necessary. The results of this study show that the use of poly(D, L-lactide) coated titanium wires with the incorporated agent gentamicin enables the establishment of antimicrobial effective gentamicin concentrations at the operation site within the first four hours after implantation. Furthermore, no signs of adverse effects of the gentamicin in the examined tissues could be observed by means of the applied radiological and histological methods. Poly (D,L- actide) and gentamicin coated osteosynthesis materials may thus be suitable for perioperative antibiotic prophylaxis, if necessary in addition to a systemic antibiotic therapy.

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Sophie Nast

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Gentamycin Immunhistochemie Implantation Infektionen Knochenbrüche Tiermodelle animal models fracture fixation fractures gentamicin immunohistochemistry infections international (MeSH) poly (lactide) (MeSH) protective coatings

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