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首页> 外文期刊>RSC Advances >A 3D bioinspired highly porous polymeric scaffolding system for in vitro simulation of pancreatic ductal adenocarcinoma
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A 3D bioinspired highly porous polymeric scaffolding system for in vitro simulation of pancreatic ductal adenocarcinoma

机译：一种用于胰腺导管腺癌的体外模拟的3D Bioinspired高度多孔聚合物脚手架系统

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摘要

Pancreatic ductal adenocarcinoma is an aggressive disease with an extremely low survival rate. This is due to the (i) poor prognosis and (ii) high resistance of the disease to current treatment options. The latter is partly due to the very complex and dense tissue/tumour microenvironment of pancreatic cancer, which contributes to the disease's progression and the inhibition of apoptotic pathways. Over the last years, advances in tissue engineering and the development of three-dimensional (3D) culture systems have shed more light into cancer research by enabling a more realistic recapitulation of the niches and structure of the tumour microenvironment. Herein, for the first time, 3D porous polyurethane scaffolds were fabricated and coated with fibronectin to mimic features of the structure and extracellular matrix present in the pancreatic cancer tumour microenvironment. The developed 3D scaffold could support the proliferation of the pancreatic tumour cells, which was enhanced with the presence of fibronectin, for a month, which is a significantly prolonged in vitro culturing duration. Furthermore, in situ imaging of cellular and biomarker distribution showed the formation of dense cellular masses, the production of collagen-I by the cells and the formation of environmental stress gradients (e.g. HIF-1) with similar heterogeneity trends to the ones reported in in vivo studies. The results obtained in this study suggest that this bioinspired porous polyurethane based scaffold has great potential for in vitro high throughput studies of pancreatic cancer including drug and treatment screening.
机译：胰腺导管腺癌是一种具有极低存活率的侵略性疾病。这是由于（i）预后差和（ii）对当前治疗方案的高抗性。后者部分是由于胰腺癌的非常复杂和致密的组织/肿瘤微环境，这有助于疾病的进展和凋亡途径的抑制。在过去几年中，组织工程的进步和三维（3D）培养系统的发展通过使肿瘤微环境的核酸和结构更加现实的综合来阐述癌症研究。在此，首次制备3D多孔聚氨酯支架并涂覆有纤连蛋白的纤连蛋白，以模拟胰腺癌肿瘤微环境中存在的结构和细胞外基质的特征。开发的3D支架可以支持胰腺肿瘤细胞的增殖，该细胞增强了纤连蛋白的存在，一个月，这是一种显着延长的体外培养持续时间。此外，在细胞和生物标志物分布的原位成像显示致密细胞块的形成，细胞产生胶原蛋白-i，并形成具有与中报告的类似的异质性趋势的环境应激梯度（例如HIF-1）体内研究。本研究中获得的结果表明，这种生物悬浮的多孔聚氨酯基支架具有巨大的胰腺癌的高通量研究，包括药物和治疗筛查。

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  • 来源
    《RSC Advances》 |2018年第37期|共13页
  • 作者

    Totti Stella; Allenby Mark C.; Dos Santos Susana Brito; Mantalaris Athanasios; Velliou Eirini G.;

  • 作者单位

    Univ Surrey Dept Chem &

    Proc Engn Bioproc &

    Biochem Engn Grp BioProChem Guildford GU2 7XH Surrey England;

    Imperial Coll London Dept Chem Engn BSEL London SW7 2AZ England;

    Imperial Coll London Dept Chem Engn BSEL London SW7 2AZ England;

    Imperial Coll London Dept Chem Engn BSEL London SW7 2AZ England;

    Univ Surrey Dept Chem &

    Proc Engn Bioproc &

    Biochem Engn Grp BioProChem Guildford GU2 7XH Surrey England;

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  • 正文语种 eng
  • 中图分类 化学;
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