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3D 生物打印和微流控芯片模型人类肝纤维化的物质世界。

The Material World of 3D-Bioprinted and Microfluidic-Chip Models of Human Liver Fibrosis.

机构信息

i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen 208, Porto, 4200-135, Portugal.

INEB - Instituto de Engenharia Biomédica, Universidade do Porto, Rua Alfredo Allen 208, Porto, 4200-135, Portugal.

出版信息

Adv Mater. 2024 Jan;36(2):e2307673. doi: 10.1002/adma.202307673. Epub 2023 Nov 22.

Abstract

Biomaterials are extensively used to mimic cell-matrix interactions, which are essential for cell growth, function, and differentiation. This is particularly relevant when developing in vitro disease models of organs rich in extracellular matrix, like the liver. Liver disease involves a chronic wound-healing response with formation of scar tissue known as fibrosis. At early stages, liver disease can be reverted, but as disease progresses, reversion is no longer possible, and there is no cure. Research for new therapies is hampered by the lack of adequate models that replicate the mechanical properties and biochemical stimuli present in the fibrotic liver. Fibrosis is associated with changes in the composition of the extracellular matrix that directly influence cell behavior. Biomaterials could play an essential role in better emulating the disease microenvironment. In this paper, the recent and cutting-edge biomaterials used for creating in vitro models of human liver fibrosis are revised, in combination with cells, bioprinting, and/or microfluidics. These technologies have been instrumental to replicate the intricate structure of the unhealthy tissue and promote medium perfusion that improves cell growth and function, respectively. A comprehensive analysis of the impact of material hints and cell-material interactions in a tridimensional context is provided.

摘要

生物材料被广泛用于模拟细胞-基质相互作用,这对于细胞的生长、功能和分化至关重要。在开发富含细胞外基质的器官的体外疾病模型时,这一点尤其重要,例如肝脏。肝脏疾病涉及慢性创伤愈合反应,形成称为纤维化的疤痕组织。在早期阶段,肝脏疾病可以逆转,但随着疾病的进展,逆转不再可能,并且没有治愈方法。由于缺乏能够复制纤维化肝脏中存在的机械性能和生化刺激的合适模型,新疗法的研究受到了阻碍。纤维化与细胞外基质组成的变化有关,这些变化直接影响细胞行为。生物材料在更好地模拟疾病微环境方面可以发挥重要作用。在本文中,我们回顾了最近用于创建人类肝纤维化体外模型的前沿生物材料,这些模型结合了细胞、生物打印和/或微流控技术。这些技术对于复制不健康组织的复杂结构以及促进改善细胞生长和功能的培养基灌注分别起到了关键作用。提供了对三维环境中材料提示和细胞-材料相互作用的影响的全面分析。

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