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辅助性 T 淋巴细胞的机械生物学模拟评估细胞-生物材料相互作用。

Mechanobiological Mimicry of Helper T Lymphocytes to Evaluate Cell-Biomaterials Crosstalk.

机构信息

Department of Chemistry and Biochemistry, University of California, Los Angeles, 607 Charles E. Young Drive South, Los Angeles, CA, 90095-1569, USA.

California NanoSystems Institute, University of California, Los Angeles, 570 Westwood Plaza, Los Angeles, CA, 90095-7227, USA.

出版信息

Adv Mater. 2018 Jun;30(23):e1706780. doi: 10.1002/adma.201706780. Epub 2018 Apr 23.

Abstract

The unique properties of immune cells have inspired many efforts in engineering advanced biomaterials capable of mimicking their behaviors. However, an inclusive model capable of mimicking immune cells in different situations remains lacking. Such models can provide invaluable data for understanding immune-biomaterial crosstalk. Inspired by CD4+ T cells, polymeric microparticles with physicochemical properties similar to naïve and active T cells are engineered. A lipid coating is applied to enhance their resemblance and provide a platform for conjugation of desired antibodies. A novel dual gelation approach is used to tune the elastic modulus and flexibility of particles, which also leads to elongated circulation times. Furthermore, the model is enriched with magnetic particles so that magnetotaxis resembles the chemotaxis of cells. Also, interleukin-2, a proliferation booster, and interferon-γ cytokines are loaded into the particles to manipulate the fates of killer T cells and mesenchymal stem cells, respectively. The penetration of these particles into 3D environments is studied to provide in vitro models of immune-biomaterials crosstalk. This biomimicry model enables optimization of design parameters required for engineering more efficient drug carriers and serves as a potent replica for understanding the mechanical behavior of immune cells.

摘要

免疫细胞的独特特性激发了许多工程先进生物材料的努力,这些材料能够模拟它们的行为。然而,仍然缺乏一种能够在不同情况下模拟免疫细胞的综合模型。这种模型可以为理解免疫-生物材料相互作用提供非常有价值的数据。受 CD4+T 细胞的启发,工程设计了具有类似于幼稚和活性 T 细胞的物理化学特性的聚合物微球。应用脂质涂层来增强它们的相似性,并提供连接所需抗体的平台。采用一种新颖的双凝胶化方法来调整颗粒的弹性模量和柔韧性,这也导致了循环时间的延长。此外,该模型中还富集了磁性颗粒,使磁趋化性类似于细胞的趋化性。此外,将白细胞介素 2(一种增殖促进剂)和干扰素-γ细胞因子加载到颗粒中,分别操纵杀伤性 T 细胞和间充质干细胞的命运。研究了这些颗粒进入 3D 环境的渗透情况,以提供免疫-生物材料相互作用的体外模型。这种仿生模型能够优化工程更有效药物载体所需的设计参数,并作为理解免疫细胞力学行为的有力复制品。

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