title: Interaction of a block-co-polymeric biomaterial with immunoglobulin G modulates human monocytes towards a non-inflammatory phenotype.
abstract: 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 chemical features of polymeric biomaterial design responsible for this process.
  
  
  CONCLUSIONS
  There is currently limited understanding of material design features that can regulate protein-material interactions in order to prevent adverse inflammatory responses to implanted biomaterials. In this paper, monocyte interactions with biomaterials (specifically a block co-polymeric degradable polyurethane [D-PHI] and tissue culture polystyrene [TCPS]) were investigated as a function of their interactions with adsorbed immunoglobulin G (IgG). D-PHI was shown to attenuate IgG-induced monocyte retention and spreading by reducing IgG-Fab site exposure upon adsorption relative to TCPS. Aspects of D-PHI chemistry important in regulating Fab site exposure were determined. This study thus identifies features of biomaterials, using D-PHI as a case study, which can contribute to the development of new immunomodulatory biomaterial design.
authors.affiliation: Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario M5S 3G9, Canada.
authors.forename: K G
authors.initials: KG
authors.lastname: Battiston
authors.affiliation: Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario M5S 3G9, Canada.
authors.forename: B
authors.initials: B
authors.lastname: Ouyang
authors.affiliation: Faculty of Dentistry, University of Toronto, Toronto, Ontario M5G 1G6, Canada.
authors.forename: E
authors.initials: E
authors.lastname: Honarparvar
authors.affiliation: Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario M5S 3G9, Canada.
authors.forename: J
authors.initials: J
authors.lastname: Qian
authors.affiliation: Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario K1H 8M5, Canada.
authors.forename: R S
authors.initials: RS
authors.lastname: Labow
authors.affiliation: Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario M5S 3G9, Canada; Faculty of Dentistry, University of Toronto, Toronto, Ontario M5G 1G6, Canada.
authors.forename: C A
authors.initials: CA
authors.lastname: Simmons
authors.affiliation: Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario M5S 3G9, Canada; Faculty of Dentistry, University of Toronto, Toronto, Ontario M5G 1G6, Canada. Electronic address: paul.santerre@dentistry.utoronto.ca.
authors.forename: J P
authors.initials: JP
authors.lastname: Santerre
mesh_terms: D063566:Biodegradable Plastics / Q000737:chemistry*; D002448:Cell Adhesion / Q000276:immunology; D020099:Coated Materials, Biocompatible / Q000737:chemistry*; D005260:Female; D005549:Foreign-Body Reaction / Q000276:immunology*; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000737:chemistry; D007074:Immunoglobulin G / Q000737:chemistry*; D008297:Male; D009000:Monocytes / Q000166:cytology / Q000276:immunology*; D011140:Polyurethanes / Q000737:chemistry*
chemical_list: D063566:Biodegradable Plastics; D020099:Coated Materials, Biocompatible; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D011140:Polyurethanes
keywords: Biomaterials; Immunoglobulin; Monocyte; Polyurethane; Protein adsorption