The human macrophage response during differentiation and biodegradation on polycarbonate-based polyurethanes: Dependence on hard segment chemistry

Human monocytes, isolated from whole blood, were seeded onto tissue culture grade polystyrene (PS) and three polycarbonate-based polyurethanes (PCNUs) (synthesized with either 1,6-hexane diisocyanate (HDI) or 4,4′-methylene bis-phenyl diisocyanate (MDI), poly(1,6-hexyl 1,2-ethyl carbonate) diol (PCN) and 1,4-butanediol (BD) in different stoichiometric ratios (HDI:PCN:BD 4:3:1 or 3:2:1 and MDI:PCN:BD 3:2:1) (referred to as HDI431, HDI321 and MDI321, respectively). Following their differentiation to monocyte-derived macrophages (MDMs) the cells were trypsinized and reseeded onto each of the PCNUs synthesized with either 14C-HDI or 14C-BD and degradation was measured by radiolabel release (RR). When the differentiation surface was MDI321, there was more RR from 14C-HDI431 than from any other surface (p<0.0001) whereas the amount of esterase (identified by immunoblotting) as well as the esterase activity was the greatest in MDM differentiated on PS, reseeded on 14C-HDI431 (p<0.0001). The effect of potential degradation products (methylene dianiline (MDA) and BD) from the PCNUs was carried out to determine possible links between products and substrate-induced activation of MDM. MDA was found to inhibit RR 60% from MDM seeded on 14C-MDI321B (p<0.0001), 20% from 14C-HDI431 (p=0.002) and no effect from 14C-HDI321B. MDA inhibited esterase activity 30% from MDM only on 14C-MDI321B (p=0.003), but no effect on esterase activity was observed for the other two polymers. BD had no inhibitory effect on RR from any PCNU, but did inhibit esterase activity in MDM on 14C-HDI431 (p=0.025). This study indicates that the degradation of a specific material is a multi-factorial process, dictated by its susceptibility to hydrolysis, the effect of specific products generated during this course of action, and perhaps not as well appreciated, the materialʹs inherent ability to influence enzyme synthesis and release.