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骨髓基质细胞与RGD修饰的三维多孔聚己内酯支架之间的相互作用。

The interaction between bone marrow stromal cells and RGD-modified three-dimensional porous polycaprolactone scaffolds.

作者信息

Zhang Huina, Lin Chia-Ying, Hollister Scott J

机构信息

Scaffold Tissue Engineering Group, Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA.

出版信息

Biomaterials. 2009 Sep;30(25):4063-9. doi: 10.1016/j.biomaterials.2009.04.015. Epub 2009 May 31.

Abstract

We previously established a simple method to immobilize the Arg-Gly-Asp (RGD) peptide on polycaprolactone (PCL) two-dimensional film surfaces that significantly improved bone marrow stromal cell (BMSC) adhesion to these films. The current work extends this modification strategy to three-dimensional (3D) PCL scaffolds to investigate BMSC attachment, cellular distribution and cellularity, signal transduction and survival on the modified PCL scaffold compared to those on the untreated ones. The results demonstrated that treatment of 3D PCL scaffold surfaces with 1,6-hexanediamine introduced the amino functional groups onto the porous PCL scaffold homogenously as detected by a ninhydrin staining method. Followed by the cross-linking reaction, RGDC peptide was successfully immobilized on the surface of PCL scaffold. Although the static seeding method used in this study caused heterogeneous cell distribution, the RGD-modified PCL scaffold still demonstrated the improved BMSC attachment and cellular distribution in the scaffold. More importantly, the integrin-mediated signal transduction FAK-PI3K-Akt pathway was significantly up-regulated by RGD modification and a subsequent increase in cell survival and growth was found in the modified scaffold. The present study introduces an easy method to immobilize RGD peptide on the 3D porous PCL scaffold and provides further evidence that modification of 3D PCL scaffolds with RGD peptides elicits specific cellular responses and improves the final cell-biomaterial interaction.

摘要

我们之前建立了一种简单的方法,可将精氨酸-甘氨酸-天冬氨酸(RGD)肽固定在聚己内酯(PCL)二维薄膜表面,这显著改善了骨髓基质细胞(BMSC)对这些薄膜的黏附。当前工作将这种修饰策略扩展到三维(3D)PCL支架,以研究与未处理的PCL支架相比,修饰后的PCL支架上BMSC的附着、细胞分布和细胞数量、信号转导及细胞存活情况。结果表明,通过茚三酮染色法检测发现,用1,6-己二胺处理3D PCL支架表面可将氨基官能团均匀引入到多孔PCL支架上。经过交联反应后,RGDC肽成功固定在PCL支架表面。尽管本研究中使用的静态接种方法导致细胞分布不均,但RGD修饰的PCL支架在支架内仍表现出改善的BMSC附着和细胞分布。更重要的是,RGD修饰显著上调了整合素介导的信号转导FAK-PI3K-Akt通路,并且在修饰后的支架中发现细胞存活和生长有所增加。本研究介绍了一种将RGD肽固定在3D多孔PCL支架上的简便方法,并进一步证明用RGD肽修饰3D PCL支架会引发特定的细胞反应并改善最终的细胞-生物材料相互作用。

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