Systematic Investigation of Polyurethane Biomaterial Surface Roughness on Human Immune Responses in vitro

Abstract

It has been widely shown that biomaterial surface topography can modulate host immune response, but a fundamental understanding of how different topographies contribute to pro-inflammatory or anti-inflammatory responses is still lacking. To investigate the impact of surface topography on immune response, we undertook a systematic approach by analyzing immune response to eight grades of medical grade polyurethane of increasing surface roughness in three in vitro models of the human immune system. Polyurethane specimens were produced with defined roughness values by injection molding according to the VDI 3400 industrial standard. Specimens ranged from 0.1 μm to 18 μm in average roughness (Ra), which was confirmed by confocal scanning microscopy. Immunological responses were assessed with THP-1-derived macrophages, human peripheral blood mononuclear cells (PBMCs), and whole blood following culture on polyurethane specimens. As shown by the release of pro-inflammatory and anti-inflammatory cytokines in all three models, a mild immune response to polyurethane was observed, however, this was not associated with the degree of surface roughness. Likewise, the cell morphology (cell spreading, circularity, and elongation) in THP-1-derived macrophages and the expression of CD molecules in the PBMC model on T cells (HLA-DR and CD16), NK cells (HLA-DR), and monocytes (HLA-DR, CD16, CD86, and CD163) showed no influence of surface roughness. In summary, this study shows that modifying surface roughness in the micrometer range on polyurethane has no impact on the pro-inflammatory immune response. Therefore, we propose that such modifications do not affect the immunocompatibility of polyurethane, thereby supporting the notion of polyurethane as a biocompatible material.

Dendritic cell biocompatibility of ether‐based urethane films

“…Altogether, these results provide evidence that the PU films are biocompatible and do not seem to be immunostimulatory to DCs. This conclusion agrees with a recent report indicating that surface roughness of polyurethane specimens had no impact on the immune response of macrophages in vitro (Segan et al, 2020). However, in a different study that used biodegradable PU nanoparticles, macrophage polarization from the M1 to M2 phenotype was inhibited, indicating that PU products may be tolerogenic in nature (Ampawong et al, 2016).…”

“…An interesting and widely studied class of polymer biomaterials is polyurethanes (PU) based on their wide structural tunability, biocompatibility, and chemical characteristics. (Huang, Hung, Hsieh, & Hsu, 2015; Segan et al, 2020).…”

The Impact of Biomaterial Cell Contact on the Immunopeptidome

“…The high failure rates with frequent rejection of implants in clinic might be decreased using in vitro immune assays to predict the outcome prior to in vivo applications (Oliveira and Mano, 2014;Kohli et al, 2018;Lock et al, 2019). There are in vitro biomaterial immunogenicity assays applied based on immature human cell lines and peripheral blood mononuclear cells (PBMCs) to assess material-induced cell viability, maturation, activation, chemotaxis, and protein secretion (Smith et al, 2009;Anderson and McNally, 2011;Franz et al, 2011;Yahyouche et al, 2011;Kou et al, 2012;Spiller et al, 2014;Sussman et al, 2014;Lock et al, 2019;Przekora, 2019;Segan et al, 2020). An increased number of HLA molecules on the cell surface is an established inflammatory marker (Park and Babensee, 2012;Musson et al, 2015), suggesting the next step, to find out which peptides are presented to T cells in higher numbers after contact with the biomaterial.…”

Curvature-induced defects on carbon-infiltrated carbon nanotube forests

“…For a blood ow application, such as mechanical heart valves or coronary stents, roughness can be directly correlated with thrombus formation; 30 however, despite roughness changes between R a ¼ 1.8 mm and 19.5 mm showing an effect on blood ow, 31 surface roughness changes in this range have shown no effect on thrombosis. 32 This may also be the case for other ow applications.…”