Grid-like surface structures in thermoplastic polyurethane induce anti-inflammatory and anti-fibrotic processes in bone marrow-derived mesenchymal stem cells

热塑性聚氨酯中的网格状表面结构可诱导骨髓间充质干细胞的抗炎和抗纤维化过程

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作者:Yvonne Roger, Luisa Marilena Schäck, Anastasia Koroleva, Sandra Noack, Kestutis Kurselis, Christian Krettek, Boris Chichkov, Thomas Lenarz, Athanasia Warnecke, Andrea Hoffmann

Abstract

The use of autologous cells for the coating of implant surfaces presents a promising tool to attenuate foreign body reaction and inflammation. However, insertion forces that occur especially during implantation of electrodes into the narrow cochlea may strip off cells from the surface. Thus, implant surfaces should be ideally structured in a way that protects the cell coating from mechanical removal during implantation. The structuring of implant surfaces may also direct cells towards desired functions to further enhance their performance and clinical suitability. In this study, grid-like square cavities were generated on thermoplastic polyurethane (TPU) surfaces using a combination of femtosecond laser ablation and replication methods. Afterwards, they were tested as potential scaffolds for human bone marrow-derived mesenchymal stem cells (MSCs) in order to use it on neural prostheses. Structured and non-structured TPU allowed proper adhesion and survival of MSCs. Surface structuring resulted in regulation of over 500 genes. Many of the upregulated genes are known to be involved in anti-inflammatory, anti-fibrotic and wound healing processes whereas genes relevant for mesenchymal differentiation programs were downregulated. The enhanced secretion of two representative factors (prostaglandin E2 and interleukin-1 receptor antagonist, respectively) was confirmed by ELISA and the downregulation of other genes involved in adipogenic and osteogenic differentiation were confirmed by gene expression analysis for a cultivation period of up to 21 days. In addition, mRNA of the surface antigens CD24 and ENDOGLIN (CD105) as representative factors for stemness did not show notable variation between cultivation on structured versus non-structured TPU or between 7 versus 21days of cultivation. Thus, surface topography of TPU seems to be a powerful tool to protect cells from mechanical forces during insertion and to influence cell behaviour.

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