Interaction of a block-co-polymeric biomaterial with immunoglobulin G modulates human monocytes towards a non-inflammatory phenotype

• Published in: Acta biomaterialia 2015-09, Vol.24, p.35-43
• Main Authors: Battiston, K.G., Ouyang, B., Honarparvar, E., Qian, J., Labow, R.S., Simmons, C.A., Santerre, J.P.
• Format: Article
• Language: English
• Subjects: Biodegradable Plastics - chemistry; Biomaterials; Biomedical materials; Cell Adhesion - immunology; Coated Materials, Biocompatible - chemistry; Degradation; Exposure; Female; Foreign-Body Reaction - immunology; Humans; Immunoglobulin; Immunoglobulin Fab Fragments - chemistry; Immunoglobulin G - chemistry; Male; Monocyte; Monocytes - cytology; Monocytes - immunology; Polyurethane; Polyurethane resins; Polyurethanes - chemistry; Protein adsorption; Surface chemistry; Surgical implants; TCP (protocol)
• ISSN: 1742-7061; 1878-7568
• DOI: 10.1016/j.actbio.2015.06.003

[Display omitted] Monocyte interactions with implanted biomaterials can contribute significantly to the ability of a biomaterial to support tissue integration and wound healing, as opposed to a chronic pro-inflammatory foreign body reaction, provided the materials are designed to do so. However, there are few biomaterials available designed to regulate immune cell response with the intention of reducing the pro-inflammatory activation state. Material chemistry is a powerful tool for regulating protein and cell interactions that can be incorporated into surfaces while maintaining desired mechanical properties. The aspects of material chemistry that can support monocyte activation away from a pro-inflammatory state are still poorly understood. Protein adsorption is a key initial event that transforms the surface of a biomedical device into a biological substrate that will govern subsequent cellular interactions. In this study, the chemistry of degradable block polyurethanes, termed degradable polar hydrophobic ionic (D-PHI) polyurethanes, were studied for their unique interactions with bound immunoglobulin G (IgG), a pro-inflammatory protein that supports monocyte–biomaterial interactions. The specific immunological active sites of the polyurethane-adsorbed protein were compared with IgG’s adsorbed state on a homopolymeric material with surface chemistry conducive to cell interactions, e.g. tissue culture polystyrene (TCPS). IgG-coated TCPS supported sustained monocyte adhesion and enhanced monocyte spreading, effects not observed with IgG-coated PU. The degradable PU was subsequently shown to reduce the number of exposed IgG-Fab sites following pre-adsorption vs. IgG adsorbed to TCPS, with antibody inhibition experiments demonstrating that Fab-site exposure appears to dominate monocyte–biomaterial interactions. Minor changes in chemical segments within the PU molecular chains were subsequently investigated for their influence on directing IgG interactions towards reducing pro-inflammatory activity. A reduction in chemical heterogeneity within the PU, without significant differences in other material properties known to regulate monocyte response, was shown to increase Fab exposure and subsequently led to monocyte interactions similar to those observed for IgG-coated TCPS. These results infer that reduced IgG-Fab site exposure can be directed by material chemistry to attenuate pro-inflammatory monocyte interactions with biomaterial surfaces, and identify the