低温集成肝组织工程生物芯片

L. Boulais, R. Jellali, U. Pereira, E. Leclerc, S. Bencherif, C. Legallais
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引用次数: 11

摘要

微流体系统和聚合物水凝胶在组织工程中得到了广泛的发展。然而,只有少数工具结合这两种方法,特别是体外肝脏模型,正在探索中。在这项研究中,设计了一种基于海藻酸盐的低温集成生物芯片,用于肝癌细胞系的三维动态培养。海藻酸盐低温凝胶在零下温度(T < 0°C)下在生物芯片中共价交联,形成具有高机械稳定性和相互连接的大孔网络的支架。通过改变海藻酸盐浓度和交联剂比例,低温凝胶的杨氏模量可以在1.5 ~ 29 kPa之间微调,对应肝脏不同生理状态下的刚度范围。我们证明HepG2/C3A细胞可以在该装置的动态条件下培养并维持存活长达6天。白蛋白合成和葡萄糖消耗随细胞培养天数的增加而增加。此外,在生物芯片的整个高度上观察到三维细胞结构,该生物芯片在海藻酸裂解酶处理后被保存下来,以去除低温支架。总之,这些结果证明了一种有趣的细胞培养技术的概念,应该进一步研究它来设计健康和肝硬化的肝脏模型。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Cryogel-Integrated Biochip for Liver Tissue Engineering
Microfluidic systems and polymer hydrogels have been widely developed for tissue engineering. Yet, only a few tools combining both approaches, especially for in vitro liver models, are being explored. In this study, an alginate-based cryogel-integrated biochip was engineered for dynamic hepatoma cell line culture in three dimensions (3D). The alginate cryogel was covalently cross-linked in the biochip at subzero temperatures (T < 0 °C) to create a scaffold with high mechanical stability and an interconnected macroporous network. By varying the alginate concentration and the cross-linker ratio, Young's modulus of the cryogel can be fine-tuned between 1.5 and 29 kPa, corresponding to the range of stiffness of the different physiological states of the liver. We demonstrated that HepG2/C3A cells can be cultured and maintained as viable under dynamic conditions in this device up to 6 days. Albumin synthesis and glucose consumption increased over the cell culture days. Moreover, a 3D cell structure was observed across the entire height of the biochip, which was preserved following alginate lyase treatment to remove the cryogel-based scaffold. In summary, these results represent a proof of concept of an interesting cell culture technology that should be further investigated to engineer healthy and cirrhotic liver models.
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