The influence of the co-monomer ratio of poly[acrylonitrile- co -( N -vinylpyrrolidone)]s on primary human monocyte-deri
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The influence of the co-monomer ratio of poly[acrylonitrile-co-(N-vinylpyrrolidone)]s on primary human monocyte-derived dendritic cells Toralf Roch, Marc Behl, Michael Zierke, Benjamin F. Pierce, Karl Kratz, Thomas Weigel, Nan Ma, and Andreas Lendlein Institute of Biomaterial Science and Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Helmholtz-Zentrum Geesthacht, Kantstraße 55, 14513 Teltow, Germany ABSTRACT A major goal in the field of regenerative medicine is to improve our understanding of how biomaterial properties affect cells of the immune system. Systematic variation of defined chemical properties could help to understand which factors determine and modulate cellular responses. A series of copolymers poly[acrylonitrile-co-(N-vinylpyrrolidone)]s (P(AN-co-NVP)) served as model system, in which increasing hydrophilicity was adjusted by increasing the content related to the NVP based repeating units (nNVP) (0, 4.6, 11.8, 22.3, and 29.4 mol%). The influence of increasing nNVP contents on cellular response of human primary monocyte derived dendritic cells (DC), which play a key role in the initiation of immune responses, was investigated. It was shown using the LAL-Test as well as a macrophage-based assay, that the materials were free of endotoxins and other microbial contaminations, which could otherwise bias the readout of the DC experiments. The increasing nNVP content led to a slightly increased cell death of DC, whereas the activation status of DC was not systematically altered by the different P(AN-co-NVP)s as demonstrated by the expression of co-stimulatory molecule and cytokine secretion. Similarly, under inflammatory conditions mimicked by the addition of lipopolysaccharides (LPS), neither the expression of co-stimulatory molecules nor the release of cytokines was influenced by the different copolymers. Conclusively, our data showed that this class of copolymers does not substantially influence the viability and the activation status of DC. INTRODUCTION Antigens and microbial products can activate DC to initiate immune responses [1]. The manipulation of the DC response is of high therapeutic interest since DC can induce anti-tumor responses, enhance the efficacy of vaccines, and could suppress auto-immune reaction [2]. Biomaterial properties such as chemical composition or surface roughness were described to influence the phenotype and activation status of DC [3, 4]. However, it is still challenging to deduce, which material properties are the most important in affecting DC phenotype. Therefore investigations, in which distinct chemical and physical materials properties are systematically altered will shed light on DC-biomaterial interactions [5]. Therefore, P(AN-co-NVP) copolymers with increasing nNVP content (4.6, 11.8, 22.3, and 29.4 mol%) showing a systematic hydrophilicity, which was documented by decreasing contact angles and an increased water uptake, were prepared. In the following, abbreviated sample IDs were used, for example nNVP 4.6 mol% refers to as with nNVP4.6. Since the P(AN-c
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