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定义用于生物医学应用的负载氧化石墨烯的 PLGA 支架的免疫相容性。

Defining the immunological compatibility of graphene oxide-loaded PLGA scaffolds for biomedical applications.

机构信息

Dipartimento di Scienze della Vita e Sanità Pubblica, Università Cattolica del Sacro Cuore, Largo Francesco Vito 1, 00168 Rome, Italy; Fondazione Policlinico Universitario A. Gemelli IRCSS, 00168 Rome, Italy.

Fondazione Policlinico Universitario A. Gemelli IRCSS, 00168 Rome, Italy; Dipartimento di Neuroscienze, Università Cattolica del Sacro Cuore, Largo Francesco Vito 1, 00168 Rome, Italy.

出版信息

Biomater Adv. 2024 Dec;165:214024. doi: 10.1016/j.bioadv.2024.214024. Epub 2024 Aug 31.

DOI:10.1016/j.bioadv.2024.214024
PMID:39232353
Abstract

Graphene oxide (GO), a carbon-based nanomaterial, presents significant potential across biomedical fields such as bioimaging, drug delivery, biosensors, and phototherapy. This study examines the effects of integrating GO into poly(lactic-co-glycolic acid) (PLGA) scaffolds on human immune cell function. Our results demonstrate that high concentrations of GO reduce the viability of peripheral blood mononuclear cells (PBMCs) following stimulation with anti-CD3 antibody. This reduction extends to T lymphocyte activation, evident from the diminished proliferative response to T cell receptor engagement and impaired differentiation into T helper subsets and regulatory T cells. Interestingly, although GO induces a minimal response in resting monocytes, but it significantly affects both the viability and the differentiation potential of monocytes induced to mature toward M1 pro-inflammatory and M2-like immunoregulatory macrophages. This study seeks to address a critical gap by investigating the in vitro immunomodulatory effects of PLGA scaffolds incorporating various concentrations of GO on primary immune cells, specifically PBMCs isolated from healthy donors. Our findings emphasize the need to optimize the GO to PLGA ratios and scaffold design to advance PLGA-GO-based biomedical applications. STATEMENT OF SIGNIFICANCE: Graphene oxide (GO) holds immense promise for biomedical applications due to its unique properties. However, concerns regarding its potential to trigger adverse immune responses remain. This study addresses this critical gap by investigating the in vitro immunomodulatory effects of PLGA scaffolds incorporating increasing GO concentrations on human peripheral blood mononuclear cells (PBMCs). By elucidating the impact on cell viability, T cell proliferation and differentiation, and the maturation/polarization of antigen-presenting cells, this work offers valuable insights for designing safe and immunologically compatible GO-based biomaterials for future clinical translation.

摘要

氧化石墨烯(GO)作为一种基于碳的纳米材料,在生物医学领域具有广泛的应用潜力,如生物成像、药物传递、生物传感器和光疗。本研究探讨了将 GO 整合到聚(乳酸-共-乙醇酸)(PLGA)支架中对人免疫细胞功能的影响。我们的结果表明,高浓度的 GO 会降低刺激抗 CD3 抗体后外周血单核细胞(PBMC)的活力。这种降低延伸到 T 淋巴细胞的激活,从 T 细胞受体结合后的增殖反应减弱和向 T 辅助细胞亚群和调节性 T 细胞分化受损可见一斑。有趣的是,尽管 GO 在静息单核细胞中引起的反应很小,但它显著影响诱导成熟为 M1 促炎和 M2 样免疫调节巨噬细胞的单核细胞的活力和分化潜能。本研究旨在通过研究含有不同浓度 GO 的 PLGA 支架对来自健康供体的 PBMC 等原代免疫细胞的体外免疫调节作用来填补这一空白。我们的研究结果强调需要优化 GO 与 PLGA 的比例和支架设计,以推进基于 PLGA-GO 的生物医学应用。

意义声明

由于其独特的性质,氧化石墨烯(GO)在生物医学应用中具有巨大的潜力。然而,人们仍然担心它有引发不良免疫反应的潜力。本研究通过研究含有不同浓度 GO 的 PLGA 支架对人外周血单核细胞(PBMC)的体外免疫调节作用,填补了这一空白。通过阐明对细胞活力、T 细胞增殖和分化以及抗原呈递细胞的成熟/极化的影响,这项工作为设计安全和免疫相容的基于 GO 的生物材料提供了有价值的见解,以便未来的临床转化。

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