Duda Franziska, Bradel Susanne, Bleich André, Abendroth Philipp, Heemeier Tanja, Ehlert Nina, Behrens Peter, Esser Karl-Heinz, Lenarz Thomas, Brandes Gudrun, Prenzler Nils K
ENT Department, Hannover Medical School, Hannover, Germany.
Institute for Laboratory Animal Science, Hannover Medical School, Hannover, Germany.
J Biomater Appl. 2015 Jul;30(1):17-29. doi: 10.1177/0885328215570103. Epub 2015 Feb 6.
For several centuries silver is known for its antibacterial effects. The middle ear is an interesting new scope for silver application since chronic inflammations combined with bacterial infection cause complete destruction of the fragile ossicle chain and tympanic membrane. The resulting conductive deafness requires tympanoplasty for reconstruction. Strategies to prevent bacterial growth on middle ear prostheses are highly recommended. In this study, rabbits were implanted with Bioverit® II middle ear prostheses functionalized with silver containing dense and nanoporous silica films which were compared with pure silica coatings as well as silver sulfadiazine cream applied on nanoporous silica coating. The health status of animals was continuously monitored; blood was examined before and after implantation. After 21 days, the middle ears were inspected; implants and mucosal samples were processed for electron microscopy. Autopsies were performed and systemic spreading of silver was chemically analyzed exemplarily in liver and kidneys. For verification of direct cytotoxicity, NIH 3T3 cells were cultured on similar silver containing silica coatings on glass up to 3 days. In vitro a reduced viability of fibroblasts adhering directly on the samples was detected compared to cells growing on the surrounding plastic of the same culture dish. In transmission electron microscopy, phagocytosed silver silica fragments, silver sulfadiazine cream as well as silver nanoparticles were noticed inside endosomes. In vivo, clinical and post mortem examinations were inconspicuous. Chemical analyses showed no increased silver content compared to controls. Mucosal coverages on almost all prostheses were found. But reduction of granulation tissue was only obvious around silver-coated implants. Single necroses and apoptosis in the mucosa were correlated by intracellular accumulation of metallic silver. For confirming supportive healing effects of middle ear implants, silver ion aggregates need to be tested in the future to optimize biocompatibility while assuring bactericidal effects in the middle ear.
几个世纪以来，银因其抗菌作用而闻名。中耳是银应用的一个有趣的新领域，因为慢性炎症与细菌感染相结合会导致脆弱的听小骨链和鼓膜完全破坏。由此产生的传导性耳聋需要进行鼓室成形术来重建。强烈推荐预防中耳假体上细菌生长的策略。在本研究中，给兔子植入了用含银的致密和纳米多孔二氧化硅膜功能化的Bioverit® II中耳假体，并将其与纯二氧化硅涂层以及应用于纳米多孔二氧化硅涂层的磺胺嘧啶银乳膏进行比较。持续监测动物的健康状况；在植入前后检查血液。21天后，检查中耳；对植入物和黏膜样本进行电子显微镜处理。进行尸检，并对肝脏和肾脏中的银的全身扩散进行化学分析。为了验证直接细胞毒性，将NIH 3T3细胞在玻璃上类似的含银二氧化硅涂层上培养长达3天。在体外，与在同一培养皿周围塑料上生长的细胞相比，检测到直接附着在样本上的成纤维细胞活力降低。在透射电子显微镜下，在内体中发现了吞噬的银二氧化硅碎片、磺胺嘧啶银乳膏以及银纳米颗粒。在体内，临床和尸检检查均未发现异常。化学分析表明，与对照组相比，银含量没有增加。几乎所有假体上都发现了黏膜覆盖。但仅在涂银植入物周围，肉芽组织的减少才明显。黏膜中的单个坏死和凋亡与金属银的细胞内积累相关。为了证实中耳植入物的支持性愈合效果，未来需要测试银离子聚集体，以优化生物相容性，同时确保中耳的杀菌效果。
