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基于聚乳酸-羟基乙酸共聚物-聚乙二醇(PLGA-PEG)纤维杨氏模量的巨噬细胞力学性能及功能调节研究

A study of macrophage mechanical properties and functional modulation based on the Young's modulus of PLGA-PEG fibers.

作者信息

Zhang Bokai, Galluzzi Massimiliano, Zhou Guoqiao, Yu Haoyang

机构信息

DGENE (Dongjin) Bighealth (Shenzhen) Co., Ltd, P.R. China.

BenHealth Biopharmaceutical (Shenzhen) Co., Ltd, P.R. China.

出版信息

Biomater Sci. 2022 Dec 20;11(1):153-161. doi: 10.1039/d2bm01351g.

Abstract

The immune response of macrophages plays an important role in defending against viral infection, tumor deterioration and repairing of contused tissue. Macrophage functional differentiation induced by nanodrugs is the leading edge of current research, but nanodrugs have toxic side effects, and the influence of their physical properties on macrophages is not clear. Here we create an alternative way to modulate macrophage function through PLGA-PEG fibers' Young's modulus. Previously, we revealed that by controlling the Young's modulus of the fibers from kPa to MPa, all the fibers entered murine macrophage cells (RWA 264.7) in a similar manner, and based on that, we found that macrophages' mechanical properties were affected by the fibers' Young's modulus, that is, hard fibers with a Young's modulus of ∼1 MPa increased the cell average Young's modulus, but did not affect the cell shape, while soft fibers with a Young's modulus of ∼100 kPa decreased the cell average Young's modulus and modulated the cell shape to a more spherical one. On the other hand, only the soft fibers induced proinflammatory cytokine secretion, indicating an M1 macrophage functional modulation by low Young's modulus fibers. This study explored the mechanical properties of the interactions between PLGA-PEG fibers and cells, in particular, when guiding the direction of the modulation of macrophage function, which is of great significance for the applications of material biology in the biomedical field.

摘要

巨噬细胞的免疫反应在抵御病毒感染、肿瘤恶化以及挫伤组织修复中发挥着重要作用。纳米药物诱导的巨噬细胞功能分化是当前研究的前沿领域,但纳米药物具有毒副作用,其物理性质对巨噬细胞的影响尚不清楚。在此,我们创造了一种通过聚乳酸-羟基乙酸共聚物-聚乙二醇(PLGA-PEG)纤维的杨氏模量来调节巨噬细胞功能的替代方法。此前,我们发现通过将纤维的杨氏模量从千帕控制到兆帕,所有纤维均以相似的方式进入小鼠巨噬细胞(RWA 264.7),基于此,我们发现巨噬细胞的力学性能受纤维杨氏模量的影响,即杨氏模量约为1兆帕的硬纤维增加了细胞的平均杨氏模量,但不影响细胞形状,而杨氏模量约为100千帕的软纤维降低了细胞的平均杨氏模量并将细胞形状调节为更接近球形。另一方面,只有软纤维诱导促炎细胞因子分泌,表明低杨氏模量纤维对M1巨噬细胞功能有调节作用。本研究探索了PLGA-PEG纤维与细胞相互作用的力学性能,特别是在指导巨噬细胞功能调节方向方面,这对材料生物学在生物医学领域的应用具有重要意义。

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