Enzyme-induced liberation of components from seven different radiolabeled polyurethanes was monitored by radiolabel counting of the incubation solutions and product isolation by high performance liquid chromatography (HPLC). The polyurethanes were selected to reflect variations in the hard-segment chemistry, soft-segment chemistry, and polyurethane hydrophilicity resulting from combinations of hydrophobic/hydrophilic soft segments. All materials were characterized using electron spectroscopy for chemical analysis, differential scanning calorimetry, size exclusion chromatography, and Fourier transform infrared spectroscopy. The material surfaces were examined both before and after incubation with enzyme and control solutions using scanning electron microscopy. Biodegradation assays were carried out at 37 degrees C using cholesterol esterase (CE) and horseradish peroxidase (HRP) under optimal pH conditions for each enzyme. The hydrolytic enzyme (CE) was effective in releasing degradation products that contained hard-segment components from some of the polyurethanes. HPLC analysis of products for a polyesterurethane synthesized with toluene diisocyanate (TDI) suggested that the bulk of the incorporated radiolabeled TDI was still covalently bonded within the cleaved chain segments of the original polymer and was not released as pure toluene diamine (TDA). The data suggest that urethane linkages in the soft-segment domains of phase separated polyetherurea-urethanes may be more prone to cleavage by CE than are the urea/urethane groups in the hard-segment domains. This could be related to the nature of the hard-segment domain structures. The oxidative enzyme (HRP) was not able to induce liberation of radiolabeled segments from either the polyether or polyester-based polyurethanes.
SYNOPSISPolyurethanes are one of the most important classes of thermoplastic elastomers and have been widely used in medical-device manufacturing as well as in other applications. However, their function can be limited, particularly under environmental conditions that render them susceptible to hydrolysis. Using polymeric additives that are hydrolytically stable may be one approach to modifying the surface of polyurethanes for the purpose of improving their hydrolytic resistance without compromising their structural features. In this paper, the development of a series of novel fluorine-containing polyurethane surface modifying macromolecules (SMMs) is described and their synthesis conditions are investigated. The material structure and mixing properties of the synthesized SMMs with base polyurethanes was dependent on the reactant stoichiometry and concentration for the SMM components, as well as the reaction temperature and the amount of catalyst used in the SMM synthesis.This study describes the use of low surface energy components (fluorinated tails) which showed selective migration towards the surface when added to a polyester-urea-urethane. These novel macromolecules generated a nonwettable surface while not significantly altering the apparent bulk structure of the base polymer. The advancing and receding contact angle results indicated that the surface of these modified polyurethanes showed wettability characteristics similar to that of Teflon.TM The differential scanning calorimetry thermograms for the mixtures of the SMM with the polyurethane showed that, a t 5% w/w SMM in the base polyurethane, the thermal transitions were similar to that of the native base polyurethane, indicating that the additives had no detectable effect on the polyurethane structure.
Monocytes are recruited to the material surface of an implanted biomedical device recognizing it as a foreign body. Differentiation into macrophages subsequently occurs followed by fusion to form foreign body giant cells (FBGCs). Consequently, implants can become degraded, cause chronic inflammation or become isolated by fibrous encapsulation. In this study, a relationship between material surface chemistry and the FBGC response was demonstrated by seeding mature monocyte-derived macrophages (MDMs) on polycarbonate-based polyurethanes that differed in their chemical structures (synthesized with poly(1,6-hexyl 1,2-ethyl carbonate) diol, and either (14)C-hexane diisocyanate and butanediol (BD) (referred to as HDI) or 4,4'-methylene bisphenyl diisocyanate and (14)C-BD (referred to as MDI)) and material degradation assessed. At 48 h of cell-material interaction, the FBGC attached to HDI were more multinucleated (73%) compared to MDI or the polystyrene (PS) control (21 and 36%, respectively). There was a fivefold increase in the synthesis and secretion of a protein with an approximate molecular weight of 48 kDa and a pI of 6.1 (determined by two-dimensional gel electrophoresis) only from cells seeded on HDI. Immunoprecipitation confirmed that MSE and CE were synthesized and secreted de novo. Immunoblotting also showed an increase in secreted monocyte-specific esterase (MSE) and cholesterol esterase (CE) from cells seeded on HDI relative to PS and MDI. Significantly more radiolabel ((14)C) release and esterase activity were elicited by MDMs on HDI than MDI (P < 0.05). The material that was more degradable (HDI), elicited greater protein synthesis and esterase secretion as well as more multinucleated MDMs than MDI, suggesting that the material surface chemistry modulates the function of MDM at the site of an inflammatory response to an implanted device.
The prominent cell type found on implanted medical devices during the chronic inflammatory response is the monocyte-derived macrophage (MDM). Using an activated in vitro cell system, it was possible to show that MDMs possess esterolytic activities that may contribute to the degradation of polyurethanes. In the present study, the U937 cell line was paralleled to the MDM cell system in order to validate the use of a cell line that could expedite studies on biomaterial biocompatibility and biostability. Using 12-o-tetradecanoylphorbol 13-acetate (PMA), the optimum differentiation time for the U937 cells was 72 h based on biodegradation, degradative potential, and (35)S-methionine uptake. After activation of the cells by resuspending from tissue culture polystyrene plates and reseeding onto a (14)C-labeled polycarbonate-based polyurethane(PCNU), both U937 cells and the MDMs elicited comparable radiolabel release (measure of polymer breakdown) and esterase activity (measure of degradative potential) at 48 h. There was no difference in the effect on radiolabel release and esterase activity elicited by both cell types with inhibitors of protein synthesis, esterase activity, and phospholipase A(2). This established that both cell types likely used similar hydrolytic activities and signaling pathways to cause degradation of the PCNU. Immunoblotting demonstrated that both cell systems secreted monocyte-specific esterase and cholesterol esterase enzymes previously shown to degrade PCNUs. The U937 cell system is more convenient and reproducible than MDMs for pursuing possible biological pathways elucidating the mechanism of polyurethane biodegradation. Once established with U937s, the pathways can then be validated with the more physiologically relevant human MDM cell system.
Polycarbonate-based polyurethanes with varying hard segment contents were synthesized. The physical and chemical structures were characterized by using gel permeation chromatography, differential scanning calorimetry, water uptake testing, Fourier transform infrared, and attenuated total reflectance--Fourier transform infrared. The polymers were incubated with cholesterol esterase in a phosphate buffer solution at 37 degrees C over 10 weeks. A higher resistance to hydrolytic degradation was observed in polycarbonate-based urethanes with higher hard segment content. The analysis of the material structures revealed that the degradation of polycarbonate-based urethanes was preferentially initiated at non-hydrogen-bonded carbonates and urethanes. Although the crystallinity of the polycarbonate soft segment may contribute to reducing the hydrolytic degradation catalyzed by cholesterol esterase, it was found to be relatively minor in comparison to the importance of hydrogen bonding between the carbonate and urethane groups. These observations suggest that the biostability of polyurethanes and specifically polycarbonate-based polyurethanes can be improved by manipulating the degree of hydrogen bonding within the materials.
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