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Biomedical subjects

J M Anderson

Publications and source records attributed to J M Anderson.

At least 145 records · Page 8Linked to original sources

In vivo biocompatibility study of ABA triblock copolymers consisting of poly(L-lactic-co-glycolic acid) A blocks attached to central poly(oxyethylene) B blocks.

Films of three ABA-block copolymers composed of lactic-co-glycolic acid A blocks and poly(oxyethylene) (PEO) B blocks and one random lactic-co-glycolic acid copolymer (PLG) were studied to investigate the influence of different polymer compositions and molecular weights on the tissue reaction, appearance of toxic degradation products, and swelling behavior in the cage implant system in rats. The inflammatory tissue reaction was followed over a 21-day implantation period by monitoring the leukocyte concentration, the extracellular acid, and alkaline phosphatase activities in a quantitative manner. Size and density of adherent macrophages and foreign body giant cells on the film surfaces were determined. The ABA and PLG implants caused only a minimal inflammatory reaction, as characterized by a low concentration of leukocytes during the implantation period when compared to empty cage controls. The content of PEO had an influence on the density of the adherent cells on the surface of the polymer film. An increase in PEO content and molecular weight decreased the cellular density during the implantation period. As demonstrated by scanning electron microscopy, no degradation was observed for all polymers during the implantation period. Our results demonstrate that the ABA block copolymers and PLG copolymer, are equally well tolerated in the cage implant test system.

Alkaline Phosphatase↗

Complement-mediated leukocyte adhesion on poly(etherurethane ureas) under shear stress in vitro.

Blood-contacting biomaterials may activate the complement cascade, thus promoting leukocyte adhesion to the biomaterial surface. We hypothesize that the extent of complement activation is modulated by biomaterial formulation and the presence of fluid shear stress. To investigate this hypothesis, we tested base poly(etherurethane ureas) formulated with or without Santowhite antioxidant, a nucleophilic additive. We found that adherent leukocyte densities decreased with increasing shear stress. Moreover, leukocyte adhesion was decreased significantly further by Santowhite additive under shear stress but not under static conditions. Monocytes showed a higher propensity for adhesion than did neutrophils under shear and static conditions. Under static conditions, adherent cells on the Santowhite-containing polyurethane had a slightly more activated morphology than those on the base polyurethane. Cell adhesion under shear stress was significantly decreased when C3 or fibronectin was depleted from the suspension medium. Santowhite additive increased Factor B adsorption to the test surface while shear stress increased Factor H adsorption. The combination of Santowhite additive and shear stress increased the adsorption of both Factor B and Factor H and the serum protein S-terminal complement complex levels, but it did not further increase the state of activation of adherent cells. We conclude that leukocyte adhesion on poly(etherurethane urea) surfaces is sensitive to the levels of shear stress and that both C3 and fibronectin are required to maintain adhesion in the presence of shear stress. The low state of cellular activation and increased Factor H adsorption may explain the decreased adherent leukocyte density on the Santowhite-containing polyurethane.

Biocompatible Materials↗

Preparation of purified atactic polypropylene and polyvinyl methyl ether surfaces for thrombogenicity studies.

Commercial samples of atactic polypropylene (aPP) and polyvinyl methyl ether (PVME) were purified and spin-cast onto glass coverslips with a view to using these as model surfaces in thrombogenicity studies. These materials differ from polyvinyl alcohol (PVA) in a single functional group and are similarly amorphous: with the same backbone they have a hydroxyl, a methoxy, or a methyl group. The objective was to understand the role of the hydroxyl group in the platelet reactivity of PVA. Surface characterization showed that they were chemically pure (as determined by X-ray photoelectron spectroscopy) but not smooth (as determined by scanning electron microscopy or interferometry), presumably due to the difficulties of spin-casting optically clear films from hot solutions (aPP or polyethylene [PE]) or because of imperfect adhesion to the saline-treated substrate (PVME). PVME was also gamma-irradiated to insolubilize it. Fewer platelets adhered to PVA than to PVME or to aPP and PE, but roughness effects and limited data preclude definitive conclusions regarding the effect of functional groups. Less protein was found on PVA than on the hydrophobic surfaces, but the significance of this observation is unclear. Further studies with more sensitive protocols are called for to examine the extent of platelet activation and its relationship to surface chemistry.

Adsorption↗

Vitamin E as an antioxidant for poly(etherurethane urea): in vivo studies. Student Research Award in the Doctoral Degree Candidate Category, Fifth World Biomaterials Congress (22nd Annual Meeting of the Society for Biomaterials), Toronto, Canada, May 29-June 2, 1996.

Poly(etherurethane) elastomers are useful materials in medical devices because of their mechanical properties and biocompatibility. However, it is necessary to stabilize these elastomers against the oxidation of their ether soft segments. Synthetic antioxidants such as Santowhite and Irganox are often satisfactory; however, particularly for biomedical applications, it was of interest to test the natural antioxidant vitamin E in poly(etherurethane urea) (PEUU) elastomers in vivo. The alpha-tocopherol form of vitamin E was added to PEUU at 5% by weight. Biaxially strained PEUU specimens with and without vitamin E were tested in vivo in the cage implant system. The influence of vitamin E on PEUU biostability was analyzed by attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy and scanning electron microscopic (SEM) characterization of the PEUU surface. ATR-FTIR results showed that vitamin E prevented chemical degradation of the PEUU surface up to 5 weeks implantation, and at 10 weeks 82% of the ether remained. In contrast, without an antioxidant, only 18% of the ether remained after 10 weeks. No surface pitting or cracking was observed by SEM on PEUU with vitamin E; PEUU without antioxidant ruptured owing to extensive pitting and cracking. It was concluded that the antioxidant properties of vitamin E prevented oxidation of strained PEUU elastomers in vivo. The influence of vitamin E on PEUU biocompatibility was characterized by exudate leukocyte counts, density of leukocytes adherent to the PEUU, and morphology of adherent leukocytes. These results indicated decreased leukocyte counts in the exudate and less active adherent cells on the PEUU with vitamin E compared to PEUU without antioxidant. A proposed cell-polymer feedback system demonstrates how vitamin E improves both biostability and biocompatibility of PEUU elastomers in vivo.

Animals↗

Influence of milrinone and norepinephrine on blood flow in canine internal mammary artery grafts.

BACKGROUND: Vasoactive agents are frequently needed in patients undergoing myocardial revascularization. The purpose of this study was to examine blood flow in the internal mammary artery (IMA) during infusion of drugs that are commonly used after myocardial revascularization. METHODS: A canine right heart bypass preparation allowed precise control of cardiac output and blood pressure, which were maintained constant during drug infusion to isolate the effect of the drug on the IMA conduit. The IMA was anastomosed to a ligated left anterior descending coronary artery. Electromagnetic flow probes measured IMA graft flow. RESULTS: Norepinephrine (0.1 microgram.kg-1.min-1) alone and when combined with phentolamine (8:5 ratio) did not alter IMA flow. Milrinone increased IMA flow 33% +/- 9%, from 37 +/- 7 to 49 +/- 10 mL/min. All hemodynamic variables were unchanged. CONCLUSIONS: The results suggest that: (1) norepinephrine did not have a deleterious effect on IMA flow and (2) milrinone may be a useful drug in patients undergoing myocardial revascularization by increasing IMA blood flow.

Animals↗

Empowering patients: issues and strategies.

Over the past few decades perspectives derived from critical social theory and other critical perspectives have infused the discourse on health, illness and healing, and have heightened awareness of the ways in which social and economic inequities experienced by particular groups determine their health. The influence of these paradigms in the health sciences occurs, simultaneously, with other movements in health care services and delivery. There has been major overhauling of health care delivery systems in many western nations with concomitant call for greater public participation and individual responsibility for health and health care (self-care). As these movements have gained momentum, ideas that suggest how people will be enabled both to attain greater social equality and to take increased responsibility for their health have flourished, and patient/consumer empowerment has become a central concept in the discourse on health. Drawing on research data from multiple sources I begin to interrogate what the notion of empowerment might mean for patients living with a chronic illness, particularly women who have immigrated to Canada; I examine the multiple layers of contexts that organize their experiences of illness. Building on earlier research that explicated the unstated ideologies that underpin the self-care movement. I extend this analysis to examine the conceptual underpinnings of "empowerment". While not dismissing the idea of "consumer empowerment" I question whether unreflexive use of this notion within the "health care industry" might deflect our attention from the structures that perpetuate social inequities. I conclude by arguing for a perspective that will allow us to address issues pertaining to the notion of empowerment in the lives of patients, generally, as well as those who are marginalized and disadvantaged.

Canada↗

Does posterior sagittal anorectoplasty in patients with high imperforate anus provide superior fecal continence?

The posterior sagittal anorectoplasty (PSARP) has become the primary surgical procedure for patients with high imperforate anus. Very few careful long-term follow-up studies have established the superiority of the PSARP procedure over other surgical repair techniques. The authors' goal was to evaluate the operation and to identify the factors associated with improved continence. The medical records, operative reports, and radiographs of 53 patients (46 male, 7 female) who underwent PSARP for high imperforate anus at Children's Hospital and Medical Center (CHMC) between 1982 and 1990 were reviewed retrospectively. Subjective follow-up data were collected by telephone questionnaire, assessing habits indicative of stool continence, and a "fecal continence score" (FCS) was calculated for each patient. A prospective, 7-day diary assessing similar patterns of fecal continence was completed by each patient's family. The mean age of the patients studied was 8.0 years, and the mean follow-up period was 6.8 years. The telephone questionnaire was completed for 48 patients (94%). Toilet training for bowel continence was successful in 20 patients (42%) and occasionally successful in another 20 patients (42%), but 8 patients (16%) had no awareness of impending stool. Forty-five (94%) were physically active, but 16 (33%) reported social problems related to offending odor. The mean fecal continence score for all patients was 3.0 +/- 1.4 (5=excellent, completely continent), which was nearly identical to published scores for the other types of surgical repair. The FCS did not improve with age. The parents' responses to the telephone questionnaire matched the results obtained from the prospectively collected continence diary data. The authors' results for PSARP in patients with high imperforate anus do not differ substantially from those achieved by other repair techniques. Previously cited prognostic factors such as fistula anatomy and sacral anomalies did not appear to alter the functional results in the authors' series. Aggressive postoperative bowel management should be anticipated in all patients who have high imperforate anus and may benefit those who otherwise would achieve less satisfactory continence.

Adolescent↗

Surface-bound heparin fails to reduce thrombin formation during clinical cardiopulmonary bypass.

The hypothesis that heparin-coated perfusion circuits reduce thrombin formation and activity; fibrinolysis; and platelet, complement, and neutrophil activation was tested in 20 consecutive, randomized adults who had cardiopulmonary bypass. Twenty identical perfusion systems were used; in 10, all blood-contacting surfaces were coated with partially degraded heparin (Carmeda process; Medtronic Cardiopulmonary, Anaheim, Calif.). All patients received a 300 U/kg dose of heparin. Activated clotting times were maintained longer than 400 seconds. Cardiopulmonary bypass lasted 36 to 244 minutes. Blood samples for platelet count, platelet response to adenosine diphosphate, plasma beta-thromboglobulin, inactivated complement 3b, neutrophil elastase, fibrinopeptide A, prothrombin fragment F1.2, thrombin-antithrombin complex, tissue plasminogen activator, plasminogen activator inhibitor-1, plasmin alpha 2-antiplasmin complex, and D-dimer were obtained at these times: after heparin was given, 5 and 30 minutes after cardiopulmonary bypass was started, within 5 minutes after bypass was stopped, and 15 minutes after protamine was given. After cardiopulmonary bypass, tubing segments were analyzed for surface-adsorbed anti-thrombin, fibrinogen, factor XII, and von Willebrand factor by radioimmunoassay. Heparin-coated circuits significantly (p < 0.001) reduced platelet adhesion and maintained platelet sensitivity to adenosine diphosphate (p = 0.015), but did not reduce release of beta-thromboglobulin. There were no significant differences between groups at any time for fibrinopeptide A, prothrombin fragment F1.2, or thrombin-antithrombin complex or in the markers for fibrinolysis: D-dimer, tissue plasminogen activator, plasminogen activator inhibitor-1, and alpha 2-antiplasmin complex. In both groups, concentrations of prothrombin fragment F1.2 and thrombin-antithrombin complex increased progressively and significantly during cardiopulmonary bypass and after protamine was given. Concentrations of D-dimer, alpha 2-antiplasmin complex, and plasminogen activator inhibitor-1 also increased significantly during bypass in both groups. Fibrinopeptide A levels did not increase during bypass but in both groups increased significantly after protamine was given. No significant differences were observed between groups for levels of inactivated complement 3b or neutrophil elastase. Radioimmunoassay showed a significant increase in surface-adsorbed antithrombin on coated circuits but no significant differences between groups for other proteins. We conclude that heparin-coated circuits used with standard doses of systemic heparin reduce platelet adhesion and improve platelet function but do not produce a meaningful anticoagulant effect during clinical cardiopulmonary bypass. The data do not support the practice of reducing systemic heparin doses during cardiac operations with heparin-coated extracorporeal perfusion circuitry.

Anticoagulants↗

Interleukin-4-induced macrophage fusion is prevented by inhibitors of mannose receptor activity.

A potential role for the macrophage mannose receptor in human monocyte-derived macrophage fusion was explored by testing the effects of previously described inhibitors of its activity on the formation of interleukin-4-induced foreign body giant cells in vitro Giant cell formation was prevented or reduced in the presence of alpha-man-nan and synthetic neoglycoprotein conjugates according to the following pattern of relative inhibition: mannose-bovine serum albumin (BSA) > N-acetylgucosamine-BSA congruent to glucose-BSA. Laminarin (beta-glucan) or galactose-BSA were not inhibitory. Swainsonine and castanospermine, inhibitors of glycoprotein processing that interfere with the arrival of newly synthesized mannose receptors at the cell surface, also attenuated macrophage fusion and the formation of giant cells, whereas another glycosidase inhibitor, deoxymannojirimycin, was without effect. Mannose receptors were confirmed to be specifically up-regulated by interleukin-4 in this culture system and also demonstrated to be present and concentrated at macrophage fusion interfaces. These data suggest that the macrophage mannose receptor may be an essential participant in the mechanism of interleukin-4-induced macrophage fusion and implicate a novel function for this endocytic/phagocytic receptor in mediating foreign body giant cell formation at sites of chronic inflammation.

Cell Fusion↗

Management of four arterial blood gas problems in adult mechanical ventilation: decision-making algorithms and rationale for their use.

Use of these algorithms does not eliminate the need to think. One must always evaluate each patient to determine if the algorithms are applicable. The algorithms provide a learning framework for any practitioner who is responsible for managing patients receiving mechanical ventilation. The effectiveness of any reference tool depends, to an extent, on the context in which it is applied. The use of these algorithms without an adequate understanding of the principles of gas exchange, acid-base balance, and the function of mechanical ventilators will probably not benefit the patient or the practitioner. The portable nature of these algorithms allows them to be used in the clinical setting. The ultimate goal, of course, is to replace the algorithms with the ability to make and justify mechanical ventilation decisions. Experience with these algorithms will also assist users in applying this approach with unfamiliar problems to find viable solutions.

Adult↗

Cytokeratin expression results in a drug-resistant phenotype to six different chemotherapeutic agents.

The cytokeratin network is an abundant cytoplasmic system whose function is largely unknown. Recently, we have found that the introduction of a cytokeratin network into eukaryotic cells results in a drug resistance phenotype. The current study was undertaken to determine the universal nature of this phenomenon by investigating the survival response of two different cell lines to six different DNA-damaging agents using two different assays of cell survival. To correlate our in vitro assays of survival with known in vivo responses to DNA damage, we compared the apoptotic response of cytokeratin-positive and cytokeratin-negative cell lines. The results show that the introduction of a cytoskeletal network confers a resistant phenotype to mitoxantrone, doxorubicin, melphalan, bleomycin, and mitomycin C in the different cytokeratin-positive cell lines. No survival advantage was noted when damage was conferred by cisplatin or UV irradiation. We found the cytokeratin-positive cell lines were protected from apoptosis, while the cell lines without cytokeratins showed apoptosis in response to mitoxantrone exposure. Cytokeratin-dependent drug resistance is observed in different cell lines but is not observed with all DNA-damaging agents. The data suggest that the mechanism of this drug resistance may be attributed, in part, to a cytokeratin-conferred protection against apoptosis.

3T3 Cells↗

Localization of the tight junction protein gene TJP1 to human chromosome 15q13, distal to the Prader-Willi/Angelman region, and to mouse chromosome 7.

The gene encoding the tight junction (zonula occludens) protein, TJP1, was mapped to human chromosome 15q13 by fluorescence in situ hybridization (FISH) using a cDNA probe. The Jackson Laboratory backcross DNA panel derived from the cross (C57BL/6JEi x SPRET/Ei) F1 females x SPRET/Ei males was used to map the mouse Tjp1 to chromosome 7 near position 30 on the Chromosome Committee Map, a region with conserved homology to human chromosome 15q13. FISH studies on metaphases from patients with the Prader-Willi (PWS) or the Angelman syndrome (AS) showed that TJP1 maps close but distal to the PWS/AS chromosome region.

Angelman Syndrome↗

Vulvar carcinoma.

PURPOSE: Controversies exist regarding the use of radiation therapy in the treatment of vulvar carcinoma. A retrospective review was performed to evaluate our institution's experience with surgery and radiation for this disease. METHODS AND MATERIALS: The medical records of 47 patients treated for squamous cell carcinoma of the vulva at our institution (1974-1992) were reviewed for TNM stage (AJCC criteria), treatment modality, and associated 5-year local control and survival based on Kaplan-Meier analysis. RESULTS: Twenty-eight patients (60%) presented with Stage I and II disease and their 5-year survival was 69%. Stage III patients accounted for 12 (25%) of the patients and their 5-year survival was 73%. Seven patients presented with Stage IV disease and five died within 13 months of diagnosis after predominantly palliative therapy. The 40 patients with Stages I, II, and III disease were treated aggressively and were further evaluated for treatment-modality-associated survival and local control. Radiation therapy was used as primary treatment in nine patients, of whom seven were treated with radiation alone and two were treated postoperatively after wide excision. Surgery alone was performed in 31 patients consisting of either radical vulvectomy (20 patients) or wide excision (11 patients). When comparing outcomes of radical vulvectomy vs. radiation therapy, we noted that the 5-year actuarial survivals were comparable (74% for either modality), despite the presence of more favorable prognostic factors in the group treated with radical vulvectomy. Patients treated with wide excision alone had a trend for a poorer 5-year actuarial survival (51%) and local control (50%). CONCLUSIONS: Radical vulvectomy offers good locoregional control and survival. This retrospective review further supports the use of radiation therapy with conservative surgery as an alternative treatment option for patients with vulvar carcinoma treated with curative intent. In contrast, the use of wide excision alone should be performed with caution due to a higher locoregional failure rate. The role of appropriately prescribed radiation therapy should be further investigated in prospective clinical trials.

Adult↗

Blood-biomaterial interactions in a flow system in the presence of bacteria: effect of protein adsorption.

An in vitro continuous flow system with whole human blood was used to study blood-biomaterial interactions on a base polyurethane and three modified surfaces in the presence and absence of circulating Staphylococcus epidermidis. We hypothesized that the composition of the protein layer adsorbed on the surface of the biomaterial would influence the response of blood components and bacteria. We examined the test surfaces for adsorption of nine plasma proteins and adsorption profiles differed on the four surfaces. The positively charged surface, UC, adsorbed significantly higher amounts of fibronectin (P < .01), von Willebrand factor (P < .01), and fibrinogen (P < .05) than the other materials. As a consequence of increased adsorption of these adhesive proteins, the adhesion of platelets and bacteria was greater on UC than on any other surface. On the base polyurethane, BC, and the negatively charged surface, UA, protein adsorption was low, and these materials were largely free of adherent blood cells and bacteria. The heparinized surface, UH, adsorbed higher quantities (P < .01) of Hageman factor and high molecular weight kininogen relative to the other surfaces. Platelet adhesion, and surface coagulation were prominent on UC, and may have contributed to increased bacterial adhesion on this surface. In the presence of circulating bacteria, adsorption was generally lower than in the absence of bacteria. The pattern of protein adsorption was largely unaffected by the strain of circulating bacteria, but platelet responses (adhesion and activation) were greater in the presence of slime-producing S. epidermidis as compared to the non-slime-producing strain, suggesting that slime may have a direct activating effect on platelets.

Adsorption↗

Human monocyte/macrophage adhesion and cytokine production on surface-modified poly(tetrafluoroethylene/hexafluoropropylene) polymers with and without protein preadsorption.

To study surface property-dependent human monocyte adhesion and cytokine (IL-1 beta, IL-6, TNF-alpha) production, poly(tetrafluoroethylene/hexafluoropropylene) (FEP) polymer was modified to exhibit neutral, anionic, or cationic properties by incorporating amide (CONH2) and/or carboxyl (COOH) or aminoethyl amide [CONH(CH2CH2NH)nCH2CH2NH2] groups on the surface. Monocyte adhesion on surface-modified FEP polymers and cytokines released by monocytes/macrophages (MC/MO) into the culture medium were compared to control tissue culture polystyrene (TCPS) at days 1 and 8. On day 1, the neutral surface FEP polymer with incorporated amide (NH2) groups showed the greatest inhibition of adhesion, 89% (P < .01), and cytokine production (IL-1 beta with 58%, IL-6 with 70%, and TNF-alpha with 39%) compared to control TCPS. In contrast, the highly cationic [CONH(CH2CH2NH)nCH2CH2NH2] surface did not show significant (P > .01) inhibition of monocyte adhesion and cytokine production. When fibrinogen or IgG was preadsorbed to the surface, the inhibitory effects of the neutral surface FEP polymer on monocyte adhesion and cytokine production were not altered. In addition, other surface-modified FEP polymers showed similar inhibition of monocyte adhesion and cytokine production compared to TCPS. Specifically, as the incorporation of carboxyl (COOH) group content increased on FEP polymer surfaces, monocyte adhesion and cytokine production were also increased on day 1 with IgG preadsorption. On day 8, all surface-modified FEP polymers showed significant (P < .01) inhibition of monocyte adhesion when fibrinogen or IgG was preadsorbed. However, without protein (fibrinogen or IgG) preadsorption, monocyte adhesion was not significantly inhibited compared to control TCPS. In addition, cytokine production detected by ELISAs on day 8 showed no detectable levels of IL-1 beta and significantly decreased levels of IL-6 compared to day 1 for all tested polymers, with or without protein preadsorption. Interestingly, the level of TNF-alpha production on day 8 remained high although not as high as on day 1. Based on these results, we suggest that FEP polymers with neutral hydrophilic surface properties may adhere and activate the least number of monocytes, which are important mediators of biocompatibility.

Adsorption↗

Oxidative biodegradation mechanisms of biaxially strained poly(etherurethane urea) elastomers.

As part of ongoing studies in polyurethane biostability and biodegradation, we have investigated an in vitro system to test strained poly(etherurethane urea) (PEUU). Recently, we utilized this system to reproduce in vivo stress cracking in strained Pellethane. In this study, strained PEUU was tested to determine whether it degrades through a common mechanism with Pellethane and to further examine the steps involved in this degradation. Biaxially strained PEUU elastomers were treated with an alpha 2-macroglobulin (alpha 2-Mac) protein solution followed by an oxidative H2O2/CoCl2 treatment. Characterization of the strained PEUU specimens was performed with attenuated total reflectance-Fourier transform infrared spectroscopy, scanning electron microscopy (SEM), electron spectroscopy for chemical analysis, and contact angle analysis. The results from these characterization techniques provide conclusive evidence that biodegradation of PEUU and Pellethane occurs through a common mechanism. Chemical changes to the PEUU include cleavage of the polyether soft segments and urethane linkages, leaving the hard segment domains unaffected. SEM analysis shows that this chain cleavage leads to the development of severe pitting and cracking of the PEUU surface. In addition, the in vitro degradation accurately reproduces the in vivo degradation chemically and physically. This result verifies that the primary species responsible for biodegradation of PEUUs, in vivo, are hydroxyl and/or hydroperoxide radicals. alpha 2-Mac pretreatment increases the rate of degradation compared to direct treatment in H2O2/CoCl2. As the PEUU soft segment chains are cleaved, the degradation products are extracted into the treatment solution or environment. Finally, a new biodegradation mechanism of PEUUs is presented that involves crosslinking of the polyether soft segments.

Adsorption↗

Adhesion and cytokine production by monocytes on poly(2-methacryloyloxyethyl phosphorylcholine-co-alkyl methacrylate)-coated polymers.

Human monocytes isolated from peripheral venous blood were assayed for their ability to adhere to various polymers. The culture supernatants were also assayed for the cytokines, interleukin-1 beta (IL-beta), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha). The polymers evaluated for adherence and cytokine production included Pellethane, polyethylene and poly[n-butyl methacrylate (BMA)] coated with poly[2-methacryloyloxyethyl phosphorylcholine (MPC)-co-alkyl methacrylate] copolymers. In some experiments the test polymers were adsorbed with fibrinogen or IgG prior to the addition of monocytes. MPC copolymer-coated materials inhibited monocyte and macrophage adhesion after 1 and 8 days of culture relative to corresponding uncoated polymers and tissue culture polystyrene (TCPS). The degree of inhibition by coated Pellethane compared to uncoated Pellethane was the greatest, while inhibition of adhesion by coated poly(BMA) was the least compared to uncoated poly(BMA). However, adhesion was significantly decreased on both coated and uncoated poly(BMA) by day 8. While IL-1 beta, IL-6, and TNF-alpha release was variably influenced by polymer coating, release was consistently inhibited relative to TCPS on day 1. However, cytokine production was not inhibited compared to corresponding uncoated polymers on day 1. With or without protein preadsorption, IL-1 beta release was not detectable in the supernatants of any polymer on day 8, IL-6 production was diminished on day 8, and TNF-alpha production was sustained on day 8. Overall, MPC copolymer-coated and uncoated poly(BMA) were the least stimulating, while TCPS was the most stimulating.(ABSTRACT TRUNCATED AT 250 WORDS)

Biocompatible Materials↗