title: Biostability and macrophage-mediated foreign body reaction of silicone-modified polyurethanes.
abstract: In this study, the effect of soft segment chemistry on the phase morphology and in vivo response of commercial-grade poly(ether urethane) (PEU), silicone-modified PEU (PEU-S), poly(carbonate urethane) (PCU), and silicone-modified PCU (PCU-S) elastomers were examined. Silicone-modified polyurethanes were developed to combine the biostability of silicone with the mechanical properties of PEUs. Results from the infrared spectroscopy confirmed the presence of silicone at the surface of the PEU-S and PCU-S films. Atomic force microscopy phase imaging indicated that the overall two-phase morphology of PEUs, necessary for its thermoplastic elastomeric properties, was not disrupted by the silicone modification. After material characterization, the in vivo foreign body response and biostability of the polyurethanes were studied using a subcutaneous cage implant protocol. The results from the cage implant study indicated that monocytes adhere, differentiate to macrophages which fuse to form foreign body giant cells on all of the polyurethanes. However, the silicone-modified surfaces promoted apoptosis of adherent macrophages at 4 days and high levels of macrophage fusion after 21 days. These results confirm that the surface of a biomaterial may influence the induction of apoptosis of adherent macrophages in vivo and are consistent with previous cell culture studies of these materials. This study validates the use of our standard cell culture protocol to predict in vivo behavior and further supports the hypothesis that interleukin-4 is the primary mediator of macrophage fusion and foreign body giant cell formation in vivo. The impact of these findings on the biostability of polyurethanes is the subject of current investigations. Attenuated total reflectance-Fourier transform infrared analysis of explanted specimens provided evidence of chain scission and crosslinking at the surface of all of the polyurethanes. The silicone modification did not fully inhibit the oxidative biodegradation of the polyether or polycarbonate soft segments; however, the rate of chain scission of PEU-S and PCU-S seemed to be slower than the control polyurethanes. To verify this finding and to quantify the rate of chain scission in order to predict long-term biostability, an in vitro environment that simulated the microenvironment at the adherent cell-material interface was used to accelerate the biodegradation of the polyurethanes. Polyurethane films were treated in vitro for up to 36 days in 20% hydrogen peroxide/0.1M cobalt chloride solution at 37 degrees Celsius. Characterization with attenuated total reflectance-Fourier transform infrared and scanning electron microscopy showed soft segment and hard segment degradation consistent with the chemical changes observed after long-term in vivo treatment. The biostability ranking of these four materials based on rate of chain scission and surface pitting was as follows: PEU < PEU-S PCU < PCU-S. The silicone modification increased the biostability of the PEU and PCU elastomers while maintaining the thermoplastic elastomeric properties.
authors.affiliation: Center for Applied Polymer Research, Case Western Reserve University, Cleveland, Ohio 44106, USA.
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Christenson
authors.forename: Mahrokh
authors.initials: M
authors.lastname: Dadsetan
authors.forename: Anne
authors.initials: A
authors.lastname: Hiltner
mesh_terms: D001672:Biocompatible Materials; D001673:Biodegradation, Environmental; D002448:Cell Adhesion; D002478:Cells, Cultured; D005549:Foreign-Body Reaction / Q000139:chemically induced* / Q000473:pathology; D008264:Macrophages / Q000166:cytology / Q000276:immunology*; D008855:Microscopy, Electron, Scanning; D011140:Polyurethanes / Q000009:adverse effects*; D012828:Silicones / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D001672:Biocompatible Materials; D011140:Polyurethanes; D012828:Silicones