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Mater Sci Eng C Mater Biol Appl. 2017 Apr 1;73:310-318. doi: 10.1016/j.msec.2016.12.087. Epub 2016 Dec 20.

Evaluation of cell-surface interaction using a 3D spheroid cell culture model on artificial extracellular matrices.

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Department of Trauma, Hand and Reconstructive Surgery, Saarland University, Building 57, 66421 Homburg, Germany. Electronic address:
Institute of Materials Science, Max Bergmann Center of Biomaterials, TU Dresden, Budapester Straße 27, 01069 Dresden, Germany.
Department of Trauma, Hand and Reconstructive Surgery, Saarland University, Building 57, 66421 Homburg, Germany.
Biomaterials Department, INNOVENT e. V., Prüssingstraße 27 B, 07745 Jena, Germany.


Since decades, cell-surface interactions are studied in 2D cell culture approaches, but cells organized in 3D (spheroids) reflect the normal situation of cells in tissues much better due to intense cell-cell-contacts. Accordingly, this study aimed to prove, if spheroids could be used to study cell-surface interaction. Spheroids consisting of fibroblasts and/or osteoblasts were seeded on artificial extracellular matrices. Here, non-sulfated hyaluronan as a biological relevant compound of the extracellular matrix was chemically sulfated to different extents and co-fibrillised with collagen. The changes of the spheroid diameters and the migration distance of outgrown cells after seeding on the matrices were used as parameters to evaluate cell-surface interaction quantitatively. Fibroblast-based spheroids reacted in the initial phase of adhesion with different spheroid sizes on the contact with the matrices. In contrast, the reaction of osteoblasts was more pronounced at later time points exhibiting a decrease of the size of the spheroids with increasing sulfation degree of the matrix. The migration of the cells was impaired by increasing sulfation degree, which might be caused by an increased expression of focal adhesion relevant proteins. In summary, spheroids can be used in cell-surface interaction studies and additional analytical tools could be implemented.


Cell-surface interaction; Glycosaminoglycans; Spheroid; Sulfated hyaluronan

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