Fischer Sebastian, Mueller Wolf, Schulte Matthias, Kiefer Jurij, Hirche Christoph, Heimer Sina, Köllensperger Eva, Germann Günter, Reichenberger Matthias A
BG Trauma Centre Ludwigshafen, Clinic for Hand, Plastic and Reconstructive Surgery, Burn Centre, Hand and Plastic Surgery of the University of Heidelberg, Heidelberg, Germany.
University Hospital Leipzig, Department of Neuropathology, University of Leipzig, Leipzig, Germany.
Ultrasound Med Biol. 2015 Mar;41(3):781-9. doi: 10.1016/j.ultrasmedbio.2014.10.018. Epub 2015 Jan 22.
Capsular fibrosis is the most frequent long-term complication after insertion of silicone devices. Today, mainly direct immunostimulation and subclinical infection are held responsible for inducing and maintaining inflammatory reactions, which lead to overwhelming extracellular matrix formation. Extracorporeal shock waves (ESWs) are capable of inhibiting inflammatory processes and revealing antibacterial capacity. In our previous study, we observed decelerated capsule development after application of a single shock wave immediately after surgery. The purpose of this study was to evaluate the effects of multiple ESWT after insertion of silicone implants in the same rodent model. Therefore, silicone prostheses were inserted into a submuscular pocket in 12 additional male Lewis rats, and shock waves were administered over a 14-d interval. At 35 d (n = 6) and 100 d (n = 6) after insertion, silicone implants and surrounding capsule tissue were removed and prepared for histologic and immunohistochemical analysis, as well as polymerase chain reaction (Ccl2, CD68, transforming growth factor β1, matrix metalloproteinase 2). Compared with the control group, multiple ESWT had no effect on day 35, but resulted in a significantly thinner capsule on day 100 (825.8 ± 313.2 vs. 813.3 ± 47.9, p = 0.759, and 1062.3 ± 151.9 vs. 495.4 ± 220.4, p < 0.001, respectively). The capsule was even thinner than after a single shock wave application, which had been found to result in thinner capsules at every time point in our previous study. This active degradation of the fibrous envelope caused by multiple ESWs was accompanied by synergistic alterations in pro- and anti-fibrotic proteins (transforming growth factor β1 and matrix metalloproteinase 2, respectively). In conclusion, after insertion of silicone devices, single ESWT is capable of decelerating capsule formation in contrast to multiple ESWT, which degrades fibrotic tissue. These findings seem to be associated with inhibition of inflammation and beneficial effects on pro- and anti-fibrotic proteins.
包膜纤维化是硅胶装置植入后最常见的长期并发症。目前,主要认为直接免疫刺激和亚临床感染是引发和维持炎症反应的原因,而炎症反应会导致大量细胞外基质形成。体外冲击波(ESW)能够抑制炎症过程并展现抗菌能力。在我们之前的研究中,我们观察到术后立即施加单次冲击波后包膜形成减缓。本研究的目的是评估在同一啮齿动物模型中硅胶植入物植入后多次体外冲击波治疗(ESWT)的效果。因此,将硅胶假体植入另外12只雄性Lewis大鼠的肌下囊袋中,并在14天的间隔内施加冲击波。植入后35天(n = 6)和100天(n = 6),取出硅胶植入物和周围的包膜组织,准备进行组织学和免疫组织化学分析,以及聚合酶链反应(Ccl2、CD68、转化生长因子β1、基质金属蛋白酶2)。与对照组相比,多次ESWT在第35天没有效果,但在第100天导致包膜明显变薄(分别为825.8±313.2与813.3±47.9,p = 0.759,以及1062.3±151.9与495.4±220.4,p < 0.001)。包膜甚至比单次冲击波治疗后更薄,在我们之前的研究中发现单次冲击波治疗在每个时间点都会导致包膜变薄。多次ESW引起的纤维包膜的这种主动降解伴随着促纤维化蛋白和抗纤维化蛋白(分别为转化生长因子β1和基质金属蛋白酶2)的协同改变。总之,硅胶装置植入后,单次ESWT能够减缓包膜形成,而多次ESWT则会降解纤维化组织。这些发现似乎与炎症抑制以及对促纤维化蛋白和抗纤维化蛋白的有益作用有关。