Fuchs Benedikt, Mert Sinan, Kuhlmann Constanze, Birt Alexandra, Hofmann Daniel, Wiggenhauser Paul Severin, Giunta Riccardo E, Chavez Myra N, Nickelsen Jörg, Schenck Thilo Ludwig, Moellhoff Nicholas
Division of Hand, Plastic and Aesthetic Surgery, LMU University Hospital, LMU Munich, 80336 Munich, Germany.
Institute of Anatomy, University of Bern, 3012 Bern, Switzerland.
J Funct Biomater. 2024 Oct 3;15(10):295. doi: 10.3390/jfb15100295.
Cyanobacteria, commonly known as blue-green algae, are prevalent in freshwater systems and have gained interest for their potential in medical applications, particularly in skin regeneration. Among these, sp. strain PCC 7002 stands out because of its rapid proliferation and capacity to be genetically modified to produce growth factors. This study investigates the safety of sp. PCC 7002 when used in scaffolds for skin regeneration, focusing on systemic inflammatory responses in a murine model. We evaluated the following three groups: scaffolds colonized with genetically engineered bacteria producing hyaluronic acid, scaffolds with wild-type bacteria, and control scaffolds without bacteria. After seven days, we assessed systemic inflammation by measuring changes in cytokine profiles and lymphatic organ sizes. The results showed no significant differences in spleen, thymus, and lymph node weights, indicating a lack of overt systemic toxicity. Blood cytokine analysis revealed elevated levels of IL-6 and IL-1β in scaffolds with bacteria, suggesting a systemic inflammatory response, while TNF-α levels remained unaffected. Proteome profiling identified distinct cytokine patterns associated with bacterial colonization, including elevated inflammatory proteins and products, indicative of acute inflammation. Conversely, control scaffolds exhibited protein profiles suggestive of a rejection response, characterized by increased levels of cytokines involved in T and B cell activation. Our findings suggest that sp. PCC 7002 does not appear to cause significant systemic toxicity, supporting its potential use in biomedical applications. Further research is necessary to explore the long-term effects and clinical implications of these responses.
蓝藻细菌，通常被称为蓝绿藻，在淡水系统中普遍存在，因其在医学应用中的潜力，特别是在皮肤再生方面的潜力而受到关注。其中，sp. 菌株PCC 7002因其快速增殖以及能够通过基因改造产生生长因子而脱颖而出。本研究调查了sp. PCC 7002用于皮肤再生支架时的安全性，重点关注小鼠模型中的全身炎症反应。我们评估了以下三组：接种产生透明质酸的基因工程菌的支架、接种野生型细菌的支架以及无细菌的对照支架。七天后，我们通过测量细胞因子谱变化和淋巴器官大小来评估全身炎症。结果显示脾脏、胸腺和淋巴结重量无显著差异，表明没有明显的全身毒性。血液细胞因子分析显示，有细菌的支架中IL-6和IL-1β水平升高，表明存在全身炎症反应，而TNF-α水平未受影响。蛋白质组分析确定了与细菌定植相关的不同细胞因子模式，包括炎症蛋白和产物水平升高，表明存在急性炎症。相反，对照支架显示出提示排斥反应的蛋白质谱，其特征是参与T和B细胞活化的细胞因子水平升高。我们的研究结果表明，sp. PCC 7002似乎不会引起明显的全身毒性，支持其在生物医学应用中的潜在用途。有必要进一步研究这些反应的长期影响和临床意义。
