Chronic osteomyelitis remains as an important and daunting orthopedic and clinical problem. Conventional treatment using systematic antibiotics is often unsuccessful. High systemic levels of aminoglycoside antibiotics also imply the risk of organ toxicity such as hearing or kidney damages.
1)One management method utilizes surgical implantation of antibiotic-impregnated poly(methyl methacrylate) (PMMA) beads into dead space created by osteomyelitic tissue removal, for local delivery of antibiotics. [2][3][4] This method intends to reach high local drug levels while maintaining low systemic levels. Gentamicin sulphate (GS)-PMMA, antibiotic-impregnated or antibiotic-loaded acrylic cements have been used in surgery to prevent or treat osteomyelitis 5) since the 1970s. A great number of studies on the amount and rate of GS release from different commercial acrylic bone cements have been published, but an insight into the mechanism and kinetics of the release process is still lacking. [6][7][8][9][10][11][12] The main aspects on which the present work is based are as follows:(i) There Exist Some Significant Differences in Behavior among the Different Antibiotic Loaded Acrylic Cement: The antibiotic release from these cements has been the subject of numerous studies. Several factors such as trade name, amount and type of antibiotic incorporated, porosity of the system, its specific area, its surface characteristics 13) and some other factors, seem to influence very markedly this release. All these facts have been the reason that the main part of these studies have yield irreconcilable results, which are analyzed with difficulty, and, in some cases, quite selfcontradictory.14-16) These apparent discrepancies require explanation. Therefore we tried to perform a reproducible study from which conclusions about the release properties of bone cements and related devices could be extracted. This information may then be used to modify the formulation in order to improve its release characteristics.(ii) Non Effective Drug Levels: It has been shown in the "in vitro" experiments that much of the antibiotic may be retained within the PMMA matrix, sometimes as much as 90% of the load. 7,9,11,16) (iii) Mechanism and Kinetics for the Precise Control of the Release Process: Due to all the above mentioned, it has not been possible to establish the mechanism and the kinetics of the GS release from commercial acrylic surgical radio opaque bone cement very clearly so far. An essential feature of the acrylic bone cements is shown in experiments carried out in vivo and in vitro by Baker and Greenham,8) who proved that PMMA bone cement that has no defects is impervious to gentamicin. In addition the glass transition of PMMA is far away above room temperature, 17) and therefore from the temperature at which the delivery experiments are carried out. From this point of view the diffusion throughout the polymeric matrix seems to be almost unfeasible.In the present study, special attention has been paid to determine the influence of the amount of...