Maja Charlotte Bohn, Hilke Oltmanns, Jessica Meißner
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引用次数: 0
Abstract
Periprosthetic joint infections (PJIs) are severe complications following surgical joint replacement and one of the main reasons for implant failure in human and veterinary medicine. Due to the global rise in antibiotic resistances and failure to prevent and treat PJIs, it is necessary to identify new antibacterial substances for the management of these infections. Methylglyoxal (MGO) is a dicarbonyl compound that has been identified as the main antibacterial component in Manuka honey. The aim of the study was to evaluate the suitability of MGO as an additive to polymethylmethacrylate bone cement in connection to PJIs. To test the antibacterial activity of pure MGO and MGO-containing bone cement against clinical isolates of Staphylococcus (S.) pseudintermedius, minimal inhibitory concentrations (MICs) were determined, growth of bacteria on bone cement was visualized, and the influence on infection of human osteosarcoma (HOS) cells was examined. Cytotoxicity of pure MGO and MGO-containing bone cement against HOS cells was analyzed with viability and proliferation assays, staining of cells on bone cement surface, and measurement of Interleukin-6 (IL-6) release. Activation of p38 MAP kinase was analyzed using Western blotting. MGO inhibited growth of S. pseudintermedius at 0.15 mg/mL, reduced bacterial colonization of bone cement at 25 mg per bone cement platelet, and reduced infection of HOS cells at 0.05 mg/mL. The IC50 of pure MGO for cell viability was 0.17 mg/mL. At higher concentrations, bone cement with MGO reduced viability and proliferation, but did not cause IL-6 release. Western blots revealed p38 activation following MGO treatment, indicating involvement of the p38 pathway in stress reactions due to the treatment. Taken together, effectiveness of MGO against PJI-relevant S. pseudintermedius could be shown but biocompatibility was limited and further research is necessary to enhance biocompatibility.
期刊介绍：
The translation of new discoveries in medicine to clinical routine has never been easy. During the second half of the last century, thanks to the progress in chemistry, biochemistry and pharmacology, we have seen the development and the application of a large number of drugs and devices aimed at the treatment of symptoms, blocking unwanted pathways and, in the case of infectious diseases, fighting the micro-organisms responsible. However, we are facing, today, a dramatic change in the therapeutic approach to pathologies and diseases. Indeed, the challenge of the present and the next decade is to fully restore the physiological status of the diseased organism and to completely regenerate tissue and organs when they are so seriously affected that treatments cannot be limited to the repression of symptoms or to the repair of damage. This is being made possible thanks to the major developments made in basic cell and molecular biology, including stem cell science, growth factor delivery, gene isolation and transfection, the advances in bioengineering and nanotechnology, including development of new biomaterials, biofabrication technologies and use of bioreactors, and the big improvements in diagnostic tools and imaging of cells, tissues and organs.
In today`s world, an enhancement of communication between multidisciplinary experts, together with the promotion of joint projects and close collaborations among scientists, engineers, industry people, regulatory agencies and physicians are absolute requirements for the success of any attempt to develop and clinically apply a new biological therapy or an innovative device involving the collective use of biomaterials, cells and/or bioactive molecules. “Frontiers in Bioengineering and Biotechnology” aspires to be a forum for all people involved in the process by bridging the gap too often existing between a discovery in the basic sciences and its clinical application.
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