PubMed Health⌕ Search

Biomedical subjects

R S Labow

Publications and source records attributed to R S Labow.

At least 19 recordsLinked to original sources

Understanding the biodegradation of polyurethanes: from classical implants to tissue engineering materials.

After almost half a century of use in the health field, polyurethanes (PUs) remain one of the most popular group of biomaterials applied for medical devices. Their popularity has been sustained as a direct result of their segmented block copolymeric character, which endows them with a wide range of versatility in terms of tailoring their physical properties, blood and tissue compatibility, and more recently their biodegradation character. While they became recognized in the 1970s and 1980s as the blood contacting material of choice in a wide range of cardiovascular devices their application in long-term implants fell under scrutiny with the failure of pacemaker leads and breast implant coatings containing PUs in the late 1980s. During the next decade PUs became extensively researched for their relative sensitivity to biodegradation and the desire to further understand the biological mechanisms for in vivo biodegradation. The advent of molecular biology into mainstream biomedical engineering permitted the probing of molecular pathways leading to the biodegradation of these materials. Knowledge gained throughout the 1990s has not only yielded novel PUs that contribute to the enhancement of biostability for in vivo long-term applications, but has also been translated to form a new class of bioresorbable materials with all the versatility of PUs in terms of physical properties but now with a more integrative nature in terms of biocompatibility. The current review will briefly survey the literature, which initially identified the problem of PU degradation in vivo and the subsequent studies that have led to the field's further understanding of the biological processes mediating the breakdown. An overview of research emerging on PUs sought for use in combination (drug + polymer) products and tissue regeneration applications will then be presented.

Absorbable Implants↗

The influence of protein adsorption and surface modifying macromolecules on the hydrolytic degradation of a poly(ether-urethane) by cholesterol esterase.

Previous investigations have demonstrated that the inflammatory cell derived enzyme, cholesterol esterase (CE) could degrade polyurethanes (PUs) by hydrolyzing ester and urethane bonds. Studies that have investigated the development of protective coatings for PUs have reported that the polymer degradation of polyester-urethanes (PESUs) can be reduced with the use of fluorine containing surface modifying macromolecules (SMMs). Since these latter studies were carried out in the presence of relatively pure enzyme, it has not been shown if SMMs would still provide an enhanced inhibitory effect if surfaces were pre-exposed to plasma proteins. This would be more representative of the in vivo scenario since protein adsorption would occur before the appearance of monocyte-derived macrophages which would be a primary source of esterase activities. The current investigation has focused on studying the influence of fibrinogen (Fg) as a simple model of protein adsorption in order to assess the effect of CE in combination with protein on polyether-urethane (PEU) surfaces. The materials were prepared with and without SMMs, and were pre-coated with Fg prior to carrying out biodegradation studies. The pre-adsorption of Fg onto the modified and non-modified surfaces provided a significant delay in the hydrolytic action of CE onto the PEU substrates. However, the effect was gone by 70 days and by the 126th day of incubation, both Fg coated and non-Fg coated groups had the same level of degradation. The difference between Fg coated and non-coated substrates was much smaller for materials containing SMMs. In addition, the pre-adsorption of Fg did not alter the SMMs' ability to provide a more biostable surface over the 4 month incubation period.

Adsorption↗

Enzyme induced biodegradation of polycarbonate-polyurethanes: dose dependence effect of cholesterol esterase.

The current study has investigated the influence of esterase activity (80-400units/ml) on the biodegradation of polycarbonate-urethanes (PCNUs) by cholesterol esterase (CE), with a particular interest in studying the influence of different hard segment structures and their contribution to sensitizing the polymer towards enzyme catalyzed hydrolysis. Polycarbonate based polyurethanes were synthesized with varying hard segment content as well as hard segment chemistry based on three different diisocyanates, 1,6-hexane diisocyanate (HDI), 4,4'-methylene bisphenyl diisocyanate (MDI) and 4,4-methylene biscyclohexyl diisocyanate (HMDI). The effect of different chemistry on surface contact angle was measured in order to define the relative chemical nature of the surfaces. The enzyme dose response was found to be lower when hard segment content in the polymer was high. There was a very strong dependence on enzyme concentration for polyurethanes with different hard segment chemistry, despite the fact that the nature of the hydrolysable polycarbonate segment remained the same. The PCNU which showed the most dramatic dependence on enzyme concentration was synthesized with HMDI. At low enzyme concentration (80units/ml) this material was the most stable of the polymers while at elevated CE concentration (400units/ml) the polymer underwent a catastrophic breakdown. The findings suggested that protein binding on the surfaces was saturated even though enzyme degradation did not achieve saturation on any of the surfaces. The role of protein binding in modulating the hydrolytic action of the enzymes at different activity levels highlights a need for further study in this area.

Cyanates↗

Isolation of methylene dianiline and aqueous-soluble biodegradation products from polycarbonate-polyurethanes.

Polycarbonate-polyurethanes (PCNUs) have provided the medical device industry with practical alternatives to oxidation-sensitive polyether-urethanes (PEUs). To date, many studies have focused on PCNUs synthesized with 4,4'-methylene diphenyl-diisocyanate (MDI). The relative hydrolytic stability of this class of polyurethanes is actually quite surprising given the inherent hydrolytic potential of the aliphatic carbonate group. Yet, there has been little information reporting on the rationale for the material's demonstrated hydrolytic stability. Recent work has shown that PCNU materials have a strong sensitivity towards hydrolysis when changes are made to their hard segment content and/or chemistry. However, knowledge is specifically lacking in regards of the identification of cleavage sites and the specific nature of the biodegradation products. Using high-performance liquid chromatography, radiolabel tracers and mass spectrometry, the current study provides insight into the distribution of biodegradation products from the enzyme-catalyzed hydrolysis of five different PCNUs. The hydrolytic sensitivity of the materials is shown to be related to the distribution of products, which itself is a direct consequence of unique micro-structures formed within the different materials. While an MDI-based polymer was shown to be the most hydrolytically stable material, it was the only PCNU that produced its diamine analog, in this case 4,4'-methylene dianiline (MDA), as a degradation product. Given the concern over aromatic diamine toxicity, this finding is important and highlights the fact that relative biostability is a distinct issue from that of degradation product toxicity, and that both must be considered separately when assessing the impact of biodegradation on biomaterial in vivo compatibility.

Aniline Compounds↗

Surface modification of a polycarbonate-urethane using a vitamin-E-derivatized fluoroalkyl surface modifier.

Fluorinated surface-modifying macromolecules (SMMs) have been previously reported on and shown to limit the hydrolytic degradation of polyurethanes. The SMM molecules achieve this effect by allowing for the selective migration of terminal fluorinated groups to the polymer's surface, which may then shield more hydrolytically-sensitive groups in the base polyurethane backbone. A further extension of the SMM concept would be to utilize the migration of the fluorine tails to simultaneously deliver biologically active moieties to the surface. This study explored the synthesis and characterization of a vitamin-E (natural anti-oxidant) coupled surface modifier, as a model for the bioactive SMM concept. The SMM was synthesized using lysine diisocyanate (LDI), polycarbonate diol (PCN), and a fluoroalcohol. By derivatizing the LDI pendant ester, vitamin E was coupled to the SMM. The vitamin-E SMM was physically characterized using gel-permeation chromatography (GPC) and its anti-oxidant activity was assessed in the presence of 0.1 mM NaOCl. Polymer degradation experiments were carried out using 10 mM NaOCl incubation solutions, and the relative material breakdown was assessed using GPC and scanning electron microscopy (SEM). The results indicate that while the fluoro-component reduced damage of the PU, the bioactive component achieved a further deactivating effect. A similar action may also be effective against superoxide anions generated by human macrophages.

Biocompatible Materials↗

The effect of polyethylene particle phagocytosis on the viability of mature human macrophages.

Macrophages are the major cell type observed in the inflammatory membrane retrieved at implant revision surgery. In this study, mature human monocyte-derived macrophages (MDM) were adapted to a previously established in vitro model to examine the influence of high-density polyethylene (HDPE) particulate (4-10 microm) on MDM viability. HDPE particles were suspended in soluble type I collagen, which subsequently was solidified on glass coverslips. Mature human macrophages, derived from differentiating peripheral blood monocytes on polystyrene for 10 days, were incubated in culture media on collagen controls and collagen-particle substrata for 31 days. Histologic analysis demonstrated that MDMs were in contact with the particles at 2 h. The majority of the particles were associated with the cells within 24 h. Based on electron microscopy, those cells associated with the particles appeared to be morphologically activated rather than necrotic or apoptotic. Assessment of cell viability revealed no differences among the groups at 24 h, but at 31 days significantly more viable cells and higher DNA values were found associated with the particle groups versus the collagen controls. The histologic results validate human mature MDMs as a clinically relevant cell type for study of the role of polyethylene particulate in aseptic loosening. The cell viability results indicate that phagocytosis of HDPE is not toxic to MDMs but in fact prolongs MDM survival. The long-lived MDMs may play a role in perpetuating chronic inflammation surrounding implants.

Cell Separation↗

Differential response to chemically altered polyethylene by activated mature human monocyte-derived macrophages.

Macrophages and polyethylene (PE) particulate are currently recognized as being the two common denominators in the development of chronic inflammation, periprosthetic osteolysis, and subsequent implant failure. In this study, the effect of PE particulate surface chemistry on mature human monocyte-derived macrophage (MDM) function was investigated. Virgin high-density PE (HDPE: 4-10 microm) and HDPE oxidized by irradiation, thermal and chemical treatment were characterized by FT-IR and suspended in soluble type I collagen, which was subsequently solidified on glass coverslips. Human MDMs, derived from differentiating monocytes on polystyrene for 14 days, were trypsinized and cultured on collagen-particle substrata and collagen controls for 31 days. Analysis of conditioned media collected at 24h incubation showed a significantly higher level of IL-1beta secretion in virgin HDPE over oxidized HDPE or collagen controls, and a significant inhibition of IL-6 secretion in both virgin and oxidized samples. Esterase activity was increased in the medium at a significantly higher level in the virgin HDPE versus controls with the highest activity observed in oxidized HDPE at 31 days. These results illustrate the effect of PE particle surface chemistry (oxidation) on MDM cytokine secretion and esterase activity, and highlight the need to further investigate the potential of PE surface chemistry on modulating MDM function.

Biocompatible Materials↗

Influence of surface morphology and chemistry on the enzyme catalyzed biodegradation of polycarbonate-urethanes.

Polycarbonate based polyurethanes were synthesized with varying hard segment content as well as hard segment chemistry based on three different diisocyanates,1,6-hexane diisocyanate (HDI), 4.4'-methylene bisphenyl diisocyanate (MDI) and 4,4-methylene biscyclohexyl diisocyanate (HMDI). The surface chemistry and morphology were characterized using X-ray photoelectron spectroscopy (XPS) and atomic force microscopy (AFM). The polymers were incubated with cholesterol esterase (CE) in a phosphate buffer solution at 37 degrees C over 10 weeks. XPS results showed that the surface chemistry changed as the size and chemistry of the hard segment varied within the materials. AFM images exhibited distinctive surface morphologies for all polymers, and this was particularly apparent with changes in the hard segment chemistry. The results showed that the surface of HDI polymers consisted of relatively stiff rod-like structures, which corresponded to the soft segment domains. Polymers with a higher HDI content exhibited a dense top layer containing a relatively higher hard segment component, covering the sub-surface matrix of rod like structures. The MDI based polyurethane had large aggregates on its top surface, which corresponded to the aggregation of harder components. The HMDI based polycarbonate-urethane presented a relatively homogeneous surface where no phase separation could be detected. The relative differences in hard and soft segment content in their surface structure was supported by XPS findings. The analysis of the biodegradation results, concluded that enzyme catalyzed biodegradation within these materials was initiated in amorphous soft segment regions located in the region of the interface between hard and soft segments. A higher hard segment content at the surface contributed significantly to an increase in biostability. The findings provided an enhanced understanding for the role of surface molecular structure in the enzyme catalyzed biodegradation of polyurethanes.

Biocompatible Materials↗

Enzyme-induced biodegradation of polycarbonate-polyurethanes: dependence on hard-segment chemistry.

Polycarbonate urethanes (PCNUs) have been used as a replacement for traditional biomedical polyether-urethanes due to their reported resistance to oxidative biodegradation. However, relatively little is known about their hydrolytic stability in the presence of inflammatory derived enzymes. This has in part motivated the current study relating to the effect of hard segment chemistry and the microdomain structures generated by such chemistry, on the cholesterol esterase (CE) catalyzed hydrolysis of PCNUs. The bulk structures of the studied materials were characterized using gel permeation chromatography (GPC), differential scanning calorimetry (DSC), small-angle X-ray scattering (SAXS), Fourier transform infrared spectroscopy (FTIR) for their bulk structures, and attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) for their subsurface structures. 14C-labeled PCNUs were incubated with CE (400 units/mL), for a period of 10 weeks (pH 7.0 at 37 degrees C), and radiolabel release was used to monitor the degradation. The results showed that all of the polymers synthesized in this study were susceptible to CE-catalyzed hydrolytic degradation, and that the extent of degradation was highly dependent on the nature of hard segment interactions within the polymer and at the surface. More specifically, the degree of phase separation and soft segment crystallinity were found to be less important in comparison to the hydrogen bonding among the carbonate and urethane linkages. The rank of the different chemical groups' susceptibility to hydrolysis was as follows: nonhydrogen bonded carbonate > nonhydrogen bonded urethane > hydrogen bonded carbonate > hydrogen bonded urethane. The findings suggest that the degree of hydrogen bonding, when processed into a polyurethane material could be an important parameter to consider in the design of new biostable polyurethane products.

Biocompatible Materials↗

Enzyme-induced biodegradation of polycarbonate polyurethanes: dependence on hard-segment concentration.

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.

Biocompatible Materials↗

Model systems to assess the destructive potential of human neutrophils and monocyte-derived macrophages during the acute and chronic phases of inflammation.

Isolated cell systems of human neutrophils (PMNs) and monocyte-derived macrophages (MDMs) were used to compare the destructive potential of these cells during the acute and chronic phases of inflammation, respectively. The contrast in the damage to poly(urethane)s (PUs) was monitored by measuring radiolabel release elicited from a (14)C-polyester-urea-urethane (PEUU) during incubation with both cell types. Human PMN were seeded onto polymer-coated glass slips and both radiolabel release as well as serine protease activity [assayed with N-benzyloxycarbonyl lysine thiobenzyl ester (BLT)] were measured 18 h later. Human monocytes were cultured on polystyrene tissue culture plates for 14 days, trypsinized, and seeded onto the polymer-coated glass slips; then, radiolabel release and esterase activity [assayed with p-nitrophenylbutyrate (PNB)] were measured after 18 h. Coverslips with MDM were also incubated for an additional 2 weeks. At 18 h postincubation with the PEUU, MDM elicited 25 times more radiolabel release per 10(6) cells than PMN at 18 h and continued to increase more than sevenfold over the 18-h value during the subsequent 14-day period. The BLT activity in PMN did not increase significantly during the 18-h incubation period, whereas the PNB activity in MDM increased more than fourfold. The MDM, but not the PMN elicited radiolabel release, was inhibited by the protein synthesis inhibitor cycloheximide, as was the increase in PNB activity. The data provide evidence for a hydrolytic role for MDM and, to a lesser extent PMN, in the biodegradation of implanted materials. The full implication of the release of polymer-derived chemical agents from this hydrolytic cleavage of the implanted biomaterials, on the propagation of the inflammatory response, remains to be elucidated.

Biocompatible Materials↗

Neutrophil-mediated biodegradation of medical implant materials.

During the acute inflammatory response to implanted medical devices, human neutrophils (PMN) release oxidative and hydrolytic activities which may ultimately contribute to the degradation of the biomaterial. In this study, the biological activities secreted by live PMNs which may contribute to biodegradation were investigated using a 14C label in the monomer unit of a poly(ester-urea-urethane) (PEUU) substrate. By using specific inhibitors, it was possible to propose a mechanism for PMN-mediated biodegradation. PMN, labeled with 3H-arachidonic acid, released significantly more 3H when adherent to PEUU than when adherent to tissue culture grade polystyrene (P<0.05). The phospholipase A2 (PLA2) inhibitors, aristolochic acid (ARIST) and quinacrine (QUIN), decreased the release of 3H and inhibited PEUU biodegradation (>50%, P<0.05). ARIST had no effect on cell viability, whereas QUIN significantly decreased it. The serine protease inhibitor, phenylmethylsulfonylfluoride inhibited biodegradation, but did not decrease cell survival. There is evidence to suggest that activation via the PLA2 pathway caused the release of hydrolytic activities which were able to elicit 14C release from PEUU. The role of oxidative compounds which were released via activation by phorbol myristate acetate (PMA), was not apparent, since PMA inhibited biodegradation and cell survival (>40%, P<0.05). This study has shown that it is possible to find out the differences in PMN activation through the PLA2 pathway when exposed to different material surfaces, making this a model system worthy of further investigation.

Aristolochic Acids↗

Hydrolytic degradation of poly(carbonate)-urethanes by monocyte-derived macrophages.

Polycarbonate (PCN)-based polyurethanes (PCNU) are rapidly becoming the chosen polyurethane (PU) for long-term implantation since they have shown decreased susceptibility to oxidation. However, monocyte-derived macrophages (MDM), the cell implicated in biodegradation, also contain hydrolytic activities. Hence, in this study, an activated human MDM cell system was used to assess the biostability of a PCNU, synthesized with 14C-hexane diisocyanate (HDI) and butanediol (BD), previously shown to be susceptible to hydrolysis by cholesterol esterase (CE). Monocytes, isolated from whole blood and cultured for 14 days on polystyrene (PS) to mature MDM, were gently trypsinized and seeded onto 14C-PCNU. Radiolabel release and esterase activity, as measured with p-nitrophenylbutyrate, increased for almost 2 weeks. At 1 week, the increase in radiolabel release and esterase activity were diminished by more than 50% when the protein synthesis inhibitor, cycloheximide, or the serine esterase/protease inhibitor, phenylmethylsulfonylfluoride was added to the medium. This strongly suggests that in part, it was MDM esterase activity which contributed to the PU degradation. In an effort to simulate the potential combination of oxidative and hydrolytic activities of inflammatory cells. 14C-PCNU was exposed to HOCl and then CE. Interestingly, the release of radiolabeled products by CE was significantly inhibited by the pre-treatment of PCNU with HOCl. The results of this study show that while the co-existing roles of oxidation and hydrolysis in the biodegradation of PCNUs remains to be elucidated, a clear relationship is drawn for PCNU degradation to the hydrolytic degradative activities which increase in MDM during differentiation from monocytes, and during activation in the chronic phase of the inflammatory response.

Biocompatible Materials↗

The effect of polyethylene particle chemistry on human monocyte-macrophage function in vitro.

Osteolysis remains the most important problem in orthopedic implant failure. Wear debris from the implant contains polyethylene (PE) particulate which has been shown to activate monocyte-derived macrophages (MDM). Although the response of MDM has been shown to be influenced by the size, shape, and chemical type of PE, the effect of chemically altered PE on MDM has not been studied. In this study, human MDM were seeded onto glass coverslips coated with virgin high density (HD)PE and chemically modified HDPE (impregnated with ppm levels of CoCl(2) and oxidized by heat) mixed with type I collagen and cultured for 96 h. Light microscopic evaluation demonstrated consistent phagocytosis of the HDPE particulate that was confirmed by scanning electron and transmission electron microscopy with little evidence of cytotoxicity. Evaluation of pro-inflammatory mediator secretion by MDMs in response to the virgin and chemically modified HDPE revealed significant differences in interleukin (IL)-1, tumor necrosis factor (TNF)-alpha, and IL-6 secretion. A significant elevation of IL-1 secretion was observed after initial exposure to virgin HDPE particles compared with controls (p = 0.001). IL-1 secretion was also elevated in the low oxidized particle groups (p = 0.001), whereas the highly oxidized particles were not different than controls. Secretion of both IL-6 (p = 0.03) and TNF-alpha (p = 0.007) were significantly elevated by the low oxidized HDPE particles whereas the virgin and highly oxidized groups showed no difference. The different effects on MDM activation when HDPE surface chemistry was altered, highlight the importance of defining the particle properties when studying the role of MDM activation in in vitro systems and extrapolating these observations to the in vivo situation.

Biocompatible Materials↗

The role of the macrophage in periprosthetic bone loss.

Aseptic loosening after total joint replacement remains the most common reason for long-term implant failure. Macrophages activated by submicron wear particles of the polyethylene liner used in joint replacement have been shown to be the source of periprosthetic bone loss. Understanding the role of material chemistry in macrophage activation and the subsequent effects that macrophage-derived enzymes play in the degradation of implanted biomaterials is key to developing methods for prolonging the lifespan of implantable materials.

Arthroplasty, Replacement↗

Hematologic evaluation of cardiopulmonary bypass circuits prepared with a novel block copolymer.

BACKGROUND: To decrease the complications associated with cardiopulmonary bypass, novel biomaterials have been introduced that may be less thrombogenic than standard synthetic surfaces. METHODS: Thirty-four patients undergoing coronary artery bypass grafting were randomized to bypass using either a control circuit or a circuit prepared "tip-to-tip" with a triblock-copolymer (polycaprolactone-polydimethylsiloxane-polycaprolactone). RESULTS: There was a progressive increase in thrombin generation in the control group during bypass, which was not seen in the test group. The test surface decreased the release of tissue plasminogen activator and plasmin-alpha2-antiplasmin complex formation (p<0.005). There was also an increased platelet count and a decreased platelet activation in the test group, as detected by GMP-140 expression and beta-thromboglobulin release (p = 0.017). There was also significantly more debris that accumulated on the arterial filter in the control group, as confirmed by scanning electron microscopy. CONCLUSIONS: This clinical trial has demonstrated a significant difference in the hematologic effects of the test circuits, with evidence of platelet preservation, decreased fibrinolysis, and decreased thrombin generation. A larger trial would be necessary to establish the clinical relevance of these differences.

Antithrombin III↗

The biodegradation of poly(urethane)s by the esterolytic activity of serine proteases and oxidative enzyme systems.

Biodegradation of poly(urethane)s (PU)s using single enzymes in vitro was assessed by measuring radiolabel release from model poly(ester-urea-urethane) (PESU) and poly(ether-urea-urethane) (PETU) materials synthesized with 14C-labelled monomers. Cholesterol esterase (CE), an enzyme found in monocyte-derived macrophages (MDM), has been reported to cause a significant level of radiolabel release from both of these PUs. Previous work has shown that CE activity could be inhibited by the serine protease/esterase inhibitor, phenylmethylsulfonyl fluoride. Since many serine proteases are present in circulating blood and can be released by cells other than MDM, this study investigated the ability of serine proteases relative to that of CE to cause the degradation of PUs. In addition, the possible role of several oxidative enzymes in the breakdown of PUs was investigated. Proteinase K, chymotrypsin and thrombin, when incubated with PESU, coated on glass slips, caused significant radiolabel release, with proteinase K giving the highest values. However, the highest radiolabel release which proteinase K could elicit was ten times less than CE. Thrombin and then chymotrypsin were progressively worse in their biodegradative activity. Only CE, and not the serine proteases, could elicit a detectable radiolabel release from PETU. Although the release of reactive oxygen species and molecular oxygen occur around an implanted biomaterial, several oxidative systems (peroxidase, xanthine oxidase, catalase), known to produce one or more of these molecular species, were unable to induce radiolabel release from these PUs. The process of biodegradation as assessed by radiolabel release appears to be a specific hydrolytic process, while the role of oxidative enzymes remains less clear.

Biodegradation, Environmental↗

Synthesis of cholesterol esterase by monocyte-derived macrophages: a potential role in the biodegradation of poly(urethane)s.

Many studies have described the role of monocyte-derived macrophages (MDM) in inflammation leading to atherosclerosis, a process in which alterations in the metabolism of cholesterol esters is well established. On the other hand, the mechanism of MDM activation in response to biomaterial surfaces is still not well understood. Several studies have described the different degrees of activation of monocytes on poly(urethane) surfaces by measuring the release of early markers of differentiation, such as cytokines. It has been possible to decrease MDM activation in contact with materials by modifying the material surface with antioxidants. Therefore, it has been proposed that it is the reactive oxygen species provided by MDM which are responsible for deleterious effects observed in material-derived inflammation. A recent study has shown that one of the markers of the degree of differentiation of MDM is the synthesis of cholesterol esterase (CE), an enzyme demonstrated as causing biodegradation of polyester(urethane)s and more recently polyether- and polycarbonate-poly(urethane)s as well. In this review article, markers used to assess MDM differentiation on material surfaces will be described and related to the activation of MDM. In particular, the CE accumulation in MDM which is associated with atherosclerosis will be related to its degradative potential during chronic inflammation. How this may impact on the biostability of implanted poly(urethane) medical devices is discussed.

Biocompatible Materials↗