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.

Highlights

  • Biomaterials have become indispensable in the field of regenerative medicine, such as in the treatment of dysfunctional joints, atherosclerotic arteries, or decaying teeth

  • This study showed that only the rougher surface to result in increased macrophage inflammatory protein-1α (MIP-1α) and monocyte chemotactic protein-1 (MCP-1) [16]

  • For this study polyurethane samples were fabricated by injection molding from steel masters with eight different roughness grades according to the VDI 3400 industrial standard, ranging from VDI 0 (“flat” with no intentional surface roughness, referred to as P0) to VDI 45 (Table 1)

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Summary

Introduction

Biomaterials have become indispensable in the field of regenerative medicine, such as in the treatment of dysfunctional joints, atherosclerotic arteries, or decaying teeth. Hybrid implants with biomimetic activity or those containing biological additives such as drug-release devices have turned into pharmacological agents according to regulatory definition and have become the subject of BioMed Research International extensive clinical trials [2]. This is contributing to a revival of pure material-based solutions based on chemical composition and intelligent surfaces. Another example is given by the use of micropatterned surfaces to control human keratocyte alignment [6], while surface topographical features can influence endothelial cell adhesion and migration [7] Together, these studies demonstrate the potential of using biomaterial surface topography to control the cellular host response

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