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载磁纳米颗粒的海藻酸钠珠用于体外组织构建的局部微驱动

Magnetic nanoparticle-loaded alginate beads for local micro-actuation of in vitro tissue constructs.

机构信息

The Catholic University of America, Department of Biomedical Engineering, United States.

The Catholic University of America, Department of Physics, United States.

出版信息

Colloids Surf B Biointerfaces. 2017 Nov 1;159:945-955. doi: 10.1016/j.colsurfb.2017.08.062. Epub 2017 Sep 4.

Abstract

Magnetic nanoparticles (MNPs) self-align and transduce magnetic force, two properties which lead to promising applications in cell and tissue engineering. However, the toxicity of MNPs to cells which uptake them is a major impediment to applications in engineered tissue constructs. To address this problem, MNPs were embedded in millimeter-scale alginate beads, coated with glutaraldehyde cross-linked chitosan, and loaded in acellular and MDA-MB-231 cancer cell-seeded collagen hydrogels, providing local micro-actuation under an external magnetic field. Brightfield microscopy was used to assess nanoparticle diffusion from the bead. Phase contrast microscopy and digital image correlation were used to track collagen matrix displacement and estimate intratissue strain under magnetic actuation. Coating the magnetic alginate beads with glutaraldehyde-chitosan prevents bulk diffusion of nanoparticles into the surrounding microenvironment. Further, the beads exert force on the surrounding collagen gel and cells, resulting in intratissue strains of 0-10% tunable with bead dimensions, collagen density, and distance from the bead. Cells seeded adjacent to the embedded beads are subjected to strain gradients without loss of cell viability over two days culture. This study describes a simple way to fabricate crosslinked magnetic alginate beads to load in a collagen tissue construct without direct exposure of the construct to nanoparticles. The findings are significant to in vitro studies of mechanobiology in enabling precise control over dynamic mechanical loading of tissue constructs.

摘要

磁性纳米颗粒(MNPs)能够自对准并传递磁力,这两种特性使其在细胞和组织工程中有广泛的应用前景。然而,细胞摄取 MNPs 后的毒性是其在工程组织构建物中应用的主要障碍。为了解决这个问题,MNPs 被嵌入毫米级大小的海藻酸盐珠中,用戊二醛交联壳聚糖涂层,并加载在无细胞和 MDA-MB-231 癌细胞接种的胶原水凝胶中,在外磁场下提供局部微驱动。明场显微镜用于评估纳米颗粒从珠体中的扩散情况。相差显微镜和数字图像相关用于跟踪胶原基质的位移,并估计磁驱动下的组织内应变。用戊二醛-壳聚糖涂覆磁性海藻酸盐珠可防止纳米颗粒大量扩散到周围的微环境中。此外,这些珠体会对周围的胶原凝胶和细胞施加力,导致组织内应变在 0-10%之间可调,可调参数包括珠体尺寸、胶原密度和距珠体的距离。在培养两天的过程中,接种到嵌入珠体附近的细胞会受到应变梯度的影响,但不会失去细胞活力。本研究描述了一种简单的方法来制备交联磁性海藻酸盐珠,以便在胶原组织构建物中加载,而无需将构建物直接暴露于纳米颗粒。这一发现对于体外机械生物学研究具有重要意义,因为它能够精确控制组织构建物的动态机械加载。

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