Polyelectrolyte microcapsules are among the most promising carriers of various sensing substances for their application inside the bloodstream of vertebrates. The long-term effects of biodegradable microcapsules in mammals are relatively well studied, but this is not the case for non-biodegradable microcapsules, which may be even more generally applicable for physiological measurements. In the current study, we introduced non-biodegradable polyelectrolyte microcapsules coated with polyethylene glycol (PMs-PEG) into the circulatory system of zebrafish to assess their long-term effects on fish internal organs with histopathologic analysis. Implantation of PMs-PEG was not associated with the formation of microclots or thrombi in thin capillaries; thus, the applied microcapsules had a low aggregation capacity. The progression of the immune response to the implant depended on the time and the abundance of microparticles in the tissues. We showed that inflammation originated from recognition and internalization of PMs-PEG by phagocytes. These microcapsule-filled immune cells have been found to migrate through the intestinal wall into the lumen, demonstrating a possible mechanism for partial microparticle elimination from fish. The observed tissue immune response to PMs-PEG was local, without a systemic effect on the fish morphology. The most pronounced chronic severe inflammatory reaction was observed near the injection site in renal parenchyma and within the abdominal cavity since PMs-PEG were administered with kidney injection. Blood clots and granulomatosis were noted at the injection site but were not found in the kidneys outside the injection site. Single microcapsules brought by blood into distal organs did not have a noticeable effect on the surrounding tissues. The severity of noted pathologies of the gills was insufficient to affect respiration. No statistically significant alterations in hepatic morphology were revealed after PMs-PEG introduction into fish body. Overall, our data demonstrate that despite they are immunogenic, non-biodegradable PMs-PEG have low potential to cause systemic effects if applied in the minimal amount necessary for detection of fluorescent signal from the microcapsules.

中文翻译：

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将不可生物降解的聚电解质微胶囊引入循环系统后，斑马鱼的组织病理学分析

聚电解质微胶囊是在脊椎动物血流中应用的各种传感物质中最有希望的载体之一。可生物降解的微囊在哺乳动物中的长期作用已得到相对较好的研究，但不可生物降解的微囊则并非如此，后者甚至更普遍地适用于生理测量。在本研究中，我们将涂有聚乙二醇（PMs-PEG）的不可生物降解的聚电解质微胶囊引入斑马鱼的循环系统，以通过组织病理学分析评估其对鱼类内部器官的长期影响。PMs-PEG的植入与薄毛细血管中微凝块或血栓的形成无关。因此，所施加的微胶囊具有低聚集能力。对植入物的免疫反应的进程取决于时间和组织中微粒的丰度。我们表明，炎症起源于吞噬细胞对PMs-PEG的识别和内在化。已经发现这些充满微胶囊的免疫细胞通过肠壁迁移到管腔中，证明了从鱼中去除部分微粒的可能机制。观察到的对PMs-PEG的组织免疫反应是局部的，对鱼类的形态没有全身性影响。由于将PMs-PEG与肾脏一起注射，因此在肾实质内注射部位附近和腹腔内观察到最明显的慢性严重炎症反应。在注射部位发现血块和肉芽肿，但在注射部位以外的肾脏中未发现。血液带入远端器官的单个微胶囊对周围组织没有明显影响。所指出的path病严重程度不足以影响呼吸。PMs-PEG引入鱼体内后，没有发现肝形态上的统计学显着变化。总的来说，我们的数据表明，尽管它们具有免疫原性，但如果以微囊中检测荧光信号所需的最小量应用，则不可生物降解的PMs-PEG具有产生全身效应的低潜力。PMs-PEG引入鱼体内后，没有发现肝形态上的统计学显着变化。总的来说，我们的数据表明，尽管它们具有免疫原性，但如果以微囊中检测荧光信号所需的最小量应用，则不可生物降解的PMs-PEG具有产生全身效应的低潜力。PMs-PEG引入鱼体内后，没有发现肝形态上的统计学显着变化。总的来说，我们的数据表明，尽管它们具有免疫原性，但如果以微囊中检测荧光信号所需的最小量应用，则不可生物降解的PMs-PEG具有产生全身效应的低潜力。