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Adhesion of fibroblast cells on thin films representing surfaces of polymeric scaffolds of human urethra rationalized by molecular models of integrin binding
Journal of Biotechnology ( IF 4.1 ) Pub Date : 2020-11-04 , DOI: 10.1016/j.jbiotec.2020.11.001
Simona Braccini 1 , Gianni Pecorini 1 , Federica Chiellini 1 , Dusan Bakos 2 , Stanislav Miertus 3 , Vladimir Frecer 4
Affiliation  

This work combines experimental and computational study of Balb/3T3 clone A31 mouse embryo fibroblasts cell line adhesion and proliferation on fourteen different polymeric surfaces prepared from poly(dioxanone) (PDO), poly(glycolic acid) (PGA), poly(hydroxybutyrate) (PHB), and poly(L-lactic acid) (PLA), and their 1:1 mixtures. The study was done with the aim to explore the attractive interactions between various synthetic biomaterials and simple model of the cell attachment mechanism involving the trans-membrane protein integrin. The considered polymeric biodegradable biomaterials can be used as scaffolds for tissue engineering and regenerative urology. During the growth of new tissue, the polymer scaffold is replaced by the extracellular matrix (ECM) synthetized by the proliferating cells. The adhesion and proliferation experiments were done on thin polymer films produced by solvent casting. The computational approach used 3D molecular models of two layers of ordered parallel polymeric fibres, which formed quasi-planar nanosized models of the scaffold surface. Experimental data showed that PGA based polymer films promote the cell adhesion. Cell proliferation testing, performed by incubating the fibroblast cells with the studied polymer films, disclosed that PLA, PHB/PLA and PHB/PGA systems are able to support proliferation of Balb/3T3 clone A31 cells equal to the plain glass. Relative interaction energies between 3D models of polymeric films and the α2 I domain of the cell adhesion receptor integrin α2β1 computed by molecular mechanics suggest that plain polymers PGA, PDO and mixtures PDO/PGA, PHB/PGA, and especially PGA/PLA display elevated affinity to the cell-attachment protein, which confirms the experimental observations. The combination of experimental and modelling approach can assist rational design of synthetic polymeric biomaterial for scaffolds of artificial human urethra that can be efficiently colonized by cells.



中文翻译:

成纤维细胞粘附在代表人尿道聚合物支架表面的薄膜上,通过整合素结合的分子模型合理化

这项工作结合了 Balb/3T3 克隆 A31 小鼠胚胎成纤维细胞细胞系在由聚二恶烷酮 (PDO)、聚乙醇酸 (PGA)、聚羟基丁酸酯 ( PHB), 和聚 ( L-乳酸)(PLA),以及它们的 1:1 混合物。该研究的目的是探索各种合成生物材料与涉及跨膜蛋白整合素的细胞附着机制的简单模型之间的有吸引力的相互作用。所考虑的聚合物可生物降解生物材料可用作组织工程和再生泌尿学的支架。在新组织的生长过程中,聚合物支架被增殖细胞合成的细胞外基质 (ECM) 取代。粘附和增殖实验是在通过溶剂浇铸生产的聚合物薄膜上进行的。计算方法使用两层有序平行聚合物纤维的 3D 分子模型,形成支架表面的准平面纳米尺寸模型。实验数据表明,基于 PGA 的聚合物薄膜促进细胞粘附。通过将成纤维细胞与所研究的聚合物膜一起孵育而进行的细胞增殖测试表明,PLA、PHB/PLA 和 PHB/PGA 系统能够支持与普通玻璃相同的 Balb/3T3 克隆 A31 细胞的增殖。聚合物薄膜 3D 模型与 α 之间的相对相互作用能通过分子力学计算的细胞粘附受体整联蛋白 α 2 β 1 的2 I 结构域表明,普通聚合物 PGA、PDO 和混合物 PDO/PGA、PHB/PGA,尤其是 PGA/PLA 显示出对细胞附着蛋白的高亲和力,这证实了实验观察。实验和建模方法的结合可以帮助合理设计合成聚合物生物材料,用于可以有效地被细胞定殖的人工人类尿道支架。

更新日期:2020-11-17
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