Nicolussi Paola, Pilo Giovannantonio, Cancedda Maria Giovanna, Peng Guotao, Chau Ngoc Do Quyen, De la Cadena Alejandro, Vanna Renzo, Samad Yarjan Abdul, Ahmed Tanweer, Marcellino Jeremia, Tedde Giuseppe, Giro Linda, Ylmazer Acelya, Loi Federica, Carta Gavina, Secchi Loredana, Dei Giudici Silvia, Macciocu Simona, Polli Dario, Nishina Yuta, Ligios Ciriaco, Cerullo Giulio, Ferrari Andrea, Bianco Alberto, Fadeel Bengt, Franzoni Giulia, Delogu Lucia Gemma
Istituto Zooprofilattico Sperimentale della Sardegna, Sassari, 07100, Italy.
Institute of Environmental Medicine, Karolinska Institutet, Stockholm, 17177, Sweden.
Adv Healthc Mater. 2025 Apr;14(10):e2401783. doi: 10.1002/adhm.202401783. Epub 2024 Oct 10.
Graphene-based materials (GBMs) are of considerable interest for biomedical applications, and the pilot study on the toxicological and immunological impact of pristine graphene (GR) and graphene oxide (GO) using swine as a close-to-human provides valuable insights. First, ex vivo experiments are conducted on swine blood cells, then GBMs are injected intraperitoneally (i.p.) into swine. Hematological and biochemical analyses at various intervals indicate that neither GO nor GR cause systemic inflammation, pro-coagulant responses, or renal or hepatic dysfunction. Importantly, no systemic toxicity is observed. Analysis of a panel of 84 immune-related genes shows minimal impact of GO and GR. The animals are sacrificed 21 days post-injection, and transient absorption imaging and Raman mapping show the presence of GO and GR in the mesentery only. Histological evaluation reveals no signs of alterations in other organs. Thus, clusters of both materials are detected in the mesentery, and GO aggregates are surrounded only by macrophages with the formation of granulomas. In contrast, modest local reactions are observed around the GR clusters. Overall, these results reveal that i.p. injection of GBMs resulted in a modest local tissue reaction without systemic toxicity. This study, performed in swine, provides essential guidance for future biomedical applications of graphene.
基于石墨烯的材料（GBMs）在生物医学应用方面备受关注，而以猪作为与人类生理特征相近的实验对象，对原始石墨烯（GR）和氧化石墨烯（GO）的毒理学和免疫学影响进行的初步研究提供了有价值的见解。首先，对猪血细胞进行体外实验，然后将GBMs经腹腔注射（i.p.）到猪体内。不同时间间隔的血液学和生化分析表明，GO和GR均不会引起全身炎症、促凝血反应或肾或肝功能障碍。重要的是，未观察到全身毒性。对一组84个免疫相关基因的分析显示，GO和GR的影响极小。在注射后21天对动物实施安乐死，瞬态吸收成像和拉曼映射显示仅在肠系膜中存在GO和GR。组织学评估未发现其他器官有改变的迹象。因此，在肠系膜中检测到两种材料的聚集体，并且GO聚集体仅被巨噬细胞包围并形成肉芽肿。相比之下，在GR聚集体周围观察到适度的局部反应。总体而言，这些结果表明腹腔注射GBMs会导致适度的局部组织反应而无全身毒性。这项在猪身上进行的研究为石墨烯未来的生物医学应用提供了重要指导。
