Woitschach Franziska, Kloss Marlen, Kischkel Sabine, Macháček Tomáš, Reinholdt Cindy, Senz Volkmar, Schlodder Karsten, Löbermann Micha, Grabow Niels, Reisinger Emil C, Sombetzki Martina
Division of Tropical Medicine and Infectious Diseases, Center of Internal Medicine II, University Medical Center, Rostock, Germany.
Institute for Biomedical Engineering, University Medical Center Rostock, Rostock-Warnemünde, Germany.
Front Bioeng Biotechnol. 2024 Apr 26;12:1367366. doi: 10.3389/fbioe.2024.1367366. eCollection 2024.
The biocompatibility of an implanted material strongly determines the subsequent host immune response. After insertion into the body, each medical device causes tissue reactions. How intense and long-lasting these are is defined by the material properties. The so-called foreign body reaction is a reaction leading to the inflammation and wound healing process after implantation. The constantly expanding field of implant technology and the growing areas of application make optimization and adaptation of the materials used inevitable. In this study, modified liquid silicone rubber (LSR) and two of the most commonly used thermoplastic polyurethanes (TPU) were compared in terms of induced inflammatory response in the body. We evaluated the production of inflammatory cytokines, infiltration of inflammatory cells and encapsulation of foreign bodies in a subcutaneous air-pouch model in mice. In this model, the material is applied in a minimally invasive procedure via a cannula and in one piece, which allows material testing without destroying or crushing the material and thus studying an intact implant surface. The study design includes short-term (6 h) and long-term (10 days) analysis of the host response to the implanted materials. Air-pouch-infiltrating cells were determined by flow cytometry after 6 h and 10 days. Inflammation, fibrosis and angiogenesis markers were analyzed in the capsular tissue by qPCR after 10 days. The foreign body reaction was investigated by macroscopic evaluation and scanning electron microscopy (SEM). Increased leukocyte infiltration was observed in the air-pouch after 6 h, but it markedly diminished after 10 days. After 10 days, capsule formations were observed around the materials without visible inflammatory cells. For biocompatibility testing materials are often implanted in muscle tissue. These test methods are not sufficiently conclusive, especially for materials that are intended to come into contact with blood. Our study primarily shows that the presented model is a highly adaptable and minimally invasive test system to test the inflammatory potential of and foreign body reaction to candidate materials and offers more precise analysis options by means of flow cytometry.
植入材料的生物相容性在很大程度上决定了随后的宿主免疫反应。将医疗设备植入体内后，每种设备都会引发组织反应。反应的强度和持续时间取决于材料特性。所谓的异物反应是植入后导致炎症和伤口愈合过程的一种反应。植入技术领域的不断扩大以及应用领域的不断增加，使得对所用材料进行优化和调整成为必然。在本研究中，对改性液态硅橡胶（LSR）和两种最常用的热塑性聚氨酯（TPU）在体内引发的炎症反应进行了比较。我们在小鼠皮下气囊模型中评估了炎性细胞因子的产生、炎性细胞的浸润以及异物的包囊情况。在该模型中，通过套管以微创方式一次性应用材料，这样可以在不破坏或挤压材料的情况下进行材料测试，从而研究完整的植入物表面。研究设计包括对宿主对植入材料反应的短期（6小时）和长期（10天）分析。在6小时和10天后，通过流式细胞术测定气囊浸润细胞。10天后，通过qPCR分析囊膜组织中的炎症、纤维化和血管生成标志物。通过宏观评估和扫描电子显微镜（SEM）研究异物反应。6小时后在气囊中观察到白细胞浸润增加，但10天后明显减少。10天后，在材料周围观察到有囊膜形成，且未见炎性细胞。对于生物相容性测试，材料通常植入肌肉组织中。这些测试方法的结论性不够充分，特别是对于那些旨在与血液接触的材料。我们的研究主要表明，所提出的模型是一种高度适应性强且微创的测试系统，可用于测试候选材料的炎症潜力和异物反应，并通过流式细胞术提供更精确的分析选项。
