A Novel Antibacterial Silicone Implant Material with Short- and Long-Term Release of Copper Ions (2010)

Sir: Capsular contracture after silicone implants is still an unresolved and serious complication. The initial adhesion of specific skin bacteria to the implant surface is believed to be the major cause of early or late infection and may also be associated with capsular contracture.1 Studies of patients with breast implants have shown that many implant pockets are germ culture-positive. The predominant isolate germs are from the local skin flora (e.g., coagulase-negative staphylococci, Propionibacterium acnes, and Corynebacterium species). Preventing implant colonization by microorganisms and formation of bacterial biofilm could be effective in improving the outcome.1,2 Various investigations with different strategies with administration of systemic antibiotics and antiseptic irrigation of the implant pocket have been performed to reduce or prevent the bacterial contamination of silicone implants.2 An alternative approach consists of implant surface modification by antimicrobial agents. With all different methods, it is fundamental not to enforce antibacterial properties at the expense of biocompatibility. The toxic effect of metal ions on either tissue cells or bacteria is well known and has been reported in multiple studies.3 Silver (Ag+) has been widely used as an antimicrobial agent in different fields of medicine. The strong antibacterial effect of Ag+ is mainly enforced at the expense of cytocompatibility.3 Heidenau et al. demonstrated in growth inhibition tests with tissue cells and bacteria that, among Al3+, Co2+, Zn2+, Hg2+, Ag+, and Cu2+, the copper ions had by far the best compromise between antibacterial effectiveness and cytotoxicity.3 Consequently, we modified the surface of silicone sheets from implants with covalent linking of 20 chitosan layers dipped in a copper solution for 1 hour (Fig. 1). Chitosan is a linear biodegradable polysaccharide with high biocompatibility. The advantage of our modification technique with chitosan layers and copper ions is that it achieves a combination of short-term and long-term release of copper ions.4Fig. 1.: Scanning electron microscopic image of a silicone surface with chitosan coating and copper additives.For quantification of bacterial adherence and to determine the proportion of live and active bacteria and dead and inactive bacteria, the LIVE/DEAD BacLight bacterial viability kit (Molecular Probes, Eugene, Ore.) was used, which provides a two-color fluorescence assay of bacterial viability.5 The silicone specimens were incubated in a Staphylococcus epidermidis suspension isolated from the human skin for 120 minutes at 4°C. Subsequently, the bacterial suspension was extracted and the silicone sheets were washed with saline to remove nonadhering bacteria. The live or dead stain was prepared in recommended proportions, so that green fluorescent staining was achieved of bacteria with intact cell membranes and red fluorescent staining was achieved of bacteria with damaged membranes. Consequently, the ratio of green to red fluorescence intensities was measured as a quantitative index of bacterial viability. In our in vitro tests, we found a significantly lower amount of adhering bacteria and a higher percentage of dead S. epidermidis on our silicone sheets with copper additive than on our pure silicone sheets (Fig. 2). Despite these preliminary results, an animal study would still be needed to confirm the antibacterial effect of our implants in vivo. Possibly we can also reduce the development and progress of capsular fibrosis.Fig. 2.: Fluorescence microscopic images by live and dead staining. Vital (green) and dead (red) staphylococci on (left) pure silicone material and (right) silicone material with copper additives (original magnification, × 200). Display window, 150 × 188 μm.Lukas Prantl, M.D., Ph.D Ralf Bürgers, D.D.S., Ph.D. Stephan Schreml, M.D. Johannes Zellner, M.D. Department of Plastic and Reconstructive Surgery Martin Gosau, M.D., D.M.D. Department of Craniomaxillofacial Surgery University Medical Center Regensburg Regensburg, Germany DISCLOSURE Dr. Prantl is one of the inventors of the new implant material and is one of the applicants for a patent. Silicone was supplied by the Mentor Corporation (Irving, Texas). ACKNOWLEDGMENTS The authors thank the Friedrich-Baur-Research Institute for Biomaterials, University of Bayreuth, Germany, for the excellent work to modify silicone sheets with copper ions for antibacterial effect. They also thank Mentor Corporation (Irving, Texas) for their generous supply of silicone material.