Biomimetic construction of peritoneum to imitate peritoneal metastasis using digital micromirror device-based optical projection lithography
Biomimetic construction of peritoneum to imitate peritoneal metastasis using digital micromirror device-based optical projection lithography
复制标题
使用基于数字微镜装置的光学投影光刻技术模拟腹膜转移的腹膜仿生结构
DOI：
10.1039/d0lc00361a
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发表时间：
2020
期刊：
影响因子：
6.1
通讯作者：
Lianqing Liu
中科院分区：
文献类型：
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作者：
Zhixing Ge;Junhua Zhao;Haibo Yu;Wenguang Yang;Peilin Zhou;Zhenning Wang;Lianqing Liu
目前，胃癌细胞腹膜转移的潜在机制和间皮细胞在此过程中的功能尚不清楚，主要是由于缺乏有效的体外腹膜模型。在本研究中，我们利用一个以数位微影装置为基础的光学投影微影系统，建构一个仿生腹膜模型。该模型能够模拟受损的腹膜，这允许将未受损的腹膜的特征（例如孔隙率、机械性能和表面形态）与受损的腹膜的特征进行比较。利用聚乙二醇二甲基丙烯酸酯水凝胶的生物惰性和可去除性来制造模拟受损人类腹膜的阵列式异质界面。腹膜的多孔结构是通过调节胶原蛋白I与甲基丙烯酰明胶的比例来实现的;腹膜的这种结构可能有助于其减震性能。原子力显微镜表征表明，模型腹膜和真实的腹膜的最外层在表面形态和力学性能上相似。此外，我们在体外复制了腹膜转移的过程。胃癌细胞在异质界面上粘附的数量不同，间皮细胞在腹膜转移中起重要作用。我们的研究结果表明，该模型可以用于临床前药物筛选和个性化治疗。
Currently, the mechanisms underlying the peritoneal metastasis of gastric cancer cells and the function of mesothelial cells during this process are unclear, primarily due to the absence of an effective in vitro peritoneal model. In this study, we constructed a biomimetic peritoneal model using a digital micromirror device-based optical projection lithography system. This model enabled the simulation of a damaged peritoneum, which allowed for a comparison of the characteristics of an undamaged peritoneum, such as porosity, mechanical properties, and surface morphology, with those of a damaged peritoneum. Biological inertness and removability of the polyethylene glycol dimethacrylate hydrogel were exploited to fabricate an arrayed heterogeneous interface that imitated a damaged human peritoneum. The porous structure of the peritoneum was achieved by adjusting the ratio of collagen I to gelatin methacryloyl; this structure of the peritoneum might contribute to its shock absorption property. Atomic force microscopy characterization showed that the outermost layers of the model peritoneum and real peritoneum were similar in surface morphology and mechanical properties. Furthermore, we reproduced the process of peritoneal metastasis in vitro. The numbers of gastric cancer cells that adhered to the heterogeneous interface were different, and mesothelial cells played an essential role in peritoneal metastasis. Our findings indicate that this model can be utilized in preclinical drug screening and personalized therapy.