|Articles about Biomaterials|
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| Biomaterial patches sutured onto the rat stomach induce a set of genes encoding pancreatic enzymes
Lobler, M., M. Sass, et al. (2002), Biomaterials 23(2): 577-83.
Abstract: Asymmetric patches of polyhydroxybutyric acid with one smooth and one rough surface were produced by a dipping procedure. These patches were implanted into the rat gastrointestine and tissue samples were generated at distinct time intervals after surgery. The host's response towards the foreign material was analyzed by Differential Display and RNA profiles were compared to each other. One to two weeks after surgery a group of mRNAs encoding pancreatic enzymes was transiently present after biomaterial implantation.
| Biomaterial pretreatment with ECGF to augment endothelial cell proliferation
Greisler, H. P., J. J. Klosak, et al. (1987), J Vasc Surg 5(2): 393-9.
Abstract: ECGF, a polypeptide of bovine hypothalamic derivation, is the most potent endothelial cell mitogen known, with mitogenic and chemotactic effects well demonstrated in vitro on human endothelial cells. These effects are synergized by heparin. In vivo re-endothelialization of blood-contacting biomaterials may be enhanced by bonding ECGF and heparin to prosthetic surfaces. Long woven Dacron (24 mm) and woven PDS vascular prostheses were treated first with human plasma fibronectin (10 micrograms/cm2). Porcine sodium heparin (20 micrograms/cm2) was added by means of fibronectin's heparin affinity. Pure 125I-ECGF (95% alpha, 5% beta; 1 ng/cm2) was next fixed by the heparin affinity of ECGF and followed by a second heparin layer (20 micrograms/cm2) to synergize with and stabilize ECGF. 125I-ECGF adherences were determined by scintillation counts. Attachment efficiency averaged 25%. Prostheses were interposed into rabbit aortas and harvested in triplicate from 0 to 30 days to establish in vivo washout curves. After explantation, residual 125I-ECGF was eluted from prostheses, and intact ECGF was identified by SDS gel electrophoresis. Similarly prepared but nonradioiodinated Dacron and PDS prostheses were explanted after 7 days and their ECGF eluted off for in vitro activity documentation. This ECGF retained its mitogenic properties, causing a 1000% to 1200% increase in 3H-thymidine incorporation into newly synthesized DNA in test murine LE-II cells. Fibronectin-heparin-ECGF fixation to blood-contacting biomaterials may enhance spontaneous re-endothelialization and/or hasten the confluence of transplanted endothelial cells.
| Biomaterial properties and biocompatibility in cell culture of a novel self-inflating hydrogel tissue expander
Wiese, K. G., D. E. Heinemann, et al. (2001), J Biomed Mater Res 54(2): 179-88.
Abstract: The aim of this study was to investigate the swelling properties and the biocompatibility of a novel tissue expander material. The self-inflating material is a hydrogel consisting of a modified copolymer of methylmethacrylate and N-vinyl-2-pyrrolidone, which takes up water by osmosis. To increase the swelling volume, the primarily neutral gel material was modified by converting it into an ionized gel. To study the swelling and pressure behavior of the material, the anhydrous gel cylinders were equilibrated in distilled water, saline, and sugar solutions. The biocompatibility was investigated in cell culture. We tested the hydrogel eluate after swelling for cytotoxicity and mutagenicity using the cell lines MRC-5 and P3X63 Ag8 653 (Ag8). Furthermore, particles of the material were added to cell cultures to induce foreign body reactions and to verify its influence on monocyte differentiation. The material has a swelling capacity (Q = maximum swelling volume/anhydrous volume) of 5 to 50 depending on the degree of ionization of the polymer network. In this study, two polymer modifications with a swelling equilibrium of Q = 11.1 and 30 in water were tested. The swelling ratio also depends on concentration and ion content of the equilibration medium. The highest swelling capacity was found in water, the lowest in Ringer's solution. The swelling of the anhydrous material with the swelling capacity of Q = 11.1 fits best the average purpose of material properties for tissue expansion and generates a maximal hydrostatic pressure of approximately 235 mmHg. Effects on cell proliferation were detected only at the highest eluate concentration tested (i.e., eluate: culture medium = 1:1), which was far beyond physiological values, whereas mutagenicity was absent. Monocytes neither migrated nor tightly attached to the hydrogel. They neither phagocytose the material nor did they show any sign of a foreign body reaction, e.g., formation of multinucleated giant cells or monocyte proliferation. In the presence of hydrogel material, the differentiation processes of monocytes to macrophages or dendritic cells, respectively, were found to be undisturbed. From these results, we conclude that there is a high biocompatibility of the expander material, which may be a favorable and interesting candidate for further clinical applications.
| Biomaterial resorption rate and healing site morphology of inorganic bovine bone and beta-tricalcium phosphate in the canine: a 24-month longitudinal histologic study and morphometric analysis
Artzi, Z., M. Weinreb, et al. (2004), Int J Oral Maxillofac Implants 19(3): 357-68.
Abstract: PURPOSE: An inorganic xenograft (inorganic bovine bone [IBB]) and a porous alloplast (beta-tricalcium phosphate [beta-TCP]) material were compared at different healing periods in experimental bone defects in dogs. MATERIALS AND METHODS: Six round defects, 5 x 4 mm, were made on the lateral bony mandibular angle in 8 dogs at different times. Two defects were randomly filled with IBB, 2 with beta-TCP, and 2 were left to blood clot. A bi-layer collagen membrane covered 1 defect of each type. Four specimens per treatment group were obtained for each treatment group at 3, 6, 12, and 24 months postoperatively. Morphometric analysis of decalcified (Donath technique) histologic slides was conducted using the measured areas of regenerated bone, grafted particles, and remaining concavity. RESULTS: In IBB sites, complete bone healing was evident at 12 and 24 months, but grafted particles dominated the sites. In beta-TCP sites, only particle remnants remained at 12 months. At 24 months, particles had completely resorbed in both membrane-protected (MP) and uncovered (UC) defects. Data were combined for final analysis since there were no statistically significant differences within each graft material group (MP or UC). Mean bone area fraction increased from 3 to 24 months at all sites. In bone area fraction a statistically significant difference was found between 3 and 6 months in the IBB and beta-TCP groups. IBB sites also showed such significance between 6 and 12 months. A statistically significant difference was found between MP ungrafted sites (42.9%) vs IBB (24.7%) and vs the control (24.8%) at 3 months. At 6 months, beta-TCP bone area fraction (68.8%) was significantly greater than IBB (47.9%) and control (37.5%) sites. At 12 months, beta-TCP bone area fraction (79.0%) was significantly greater than the control (42.5%). At 24 months, beta-TCP bone area fraction (86.5%) was significantly greater than IBB (55.6%) sites. Mean particle area fraction of beta-TCP sites decreased gradually until complete resorption at 24 months. IBB sites showed a significant decrease only between 3 (38.7%) and 6 (29.4%) months. DISCUSSION AND CONCLUSION: Complete bone healing was established in all grafted defects. IBB and beta-TCP are both excellent biocompatible materials. However, at 24 months beta-TCP particles were completely resorbed, whereas IBB particles still occupied a remarkable area fraction without significant resorption beyond 6 months. (More than 50 references.)
| Biomaterial supports for colonic wall defect healing. An experimental study in the rat
Mutter, D., M. Aprahamian, et al. (1996), Biomaterials 17(14): 1411-5.
Abstract: New artificial biomaterials were tested for support of gastro-intestinal tract wound healing in the rat. Double layered collagenic matrices were prepared with purified collagens extracted from human placental tissues. Two types of patches were tested, the first constituted from a collagen type I + III layer covered by collagen IV in a liquid phase (patch I + III/IV) and the second from a collagen IV layer covered by liquid collagen IV (patch IV/IV). The matrices were applied with fibrin sealant to the edges of a 1 cm diameter colonic wall defect in the rat. Healing evolution was determined by macroscopic, microscopic and immunostaining studies. The reconstitution of the three colonic wall layers was achieved within 45 days without retraction or inflammatory reaction, while the biomaterial was resorbed. Human collagen I and III antibodies failed to stain extracellular matrix. This failure may be a consequence of outdated antibodies or more likely epitope alteration during extraction and preparation of the collagens. A human collagen type IV antibody staining of the scar zone showed the basement membranes of newly developed vessels within 10 days, and newly formed colonic mucosa within 20 days. The collagen reconstituted matrix was able to assist healing of normal digestive tract defects as shown by the labelling of the new synthesized extracellular matrix by collagen type IV antibody. These findings support the use of collagen biomaterial in gastro-intestinal anastomosis. This new surgical approach allowing healing of colonic wall defects could reduce occurrence of anastomotic leakage in human.
| Biomaterial surface chemistry dictates adherent monocyte/macrophage cytokine expression in vitro
Brodbeck, W. G., Y. Nakayama, et al. (2002), Cytokine 18(6): 311-9.
Abstract: An in vitro human monocyte culture system was used to determine whether adherent monocyte/macrophage cytokine production was influenced by material surface chemistry. A polyethylene terephthalate (PET) base surface was modified by photograft copolymerization to yield hydrophobic, hydrophilic, anionic and cationic surfaces. Freshly isolated human monocytes were cultured onto the surfaces for periods up to 10 days in the presence or absence of interleukin-4 (IL-4). Semi-quantitative RT-PCR analysis on days 3, 7 and 10 of cell culture revealed that interleukin-10 (IL-10) expression significantly increased in cells adherent to the hydrophilic and anionic surfaces but significantly decreased in the cationic surface adherent monocytes/macrophages. Conversely, interleukin-8 (IL-8) expression was significantly decreased in cells adherent to the hydrophilic and anionic surfaces. Further analysis revealed that the hydrophilic and anionic surfaces inhibited monocyte adhesion and IL-4-mediated macrophage fusion into foreign body giant cells (FBGCs). Therefore, hydrophilic and anionic surfaces promote an anti-inflammatory type of response by dictating selective cytokine production by biomaterial adherent monocytes and macrophages. These studies contribute information necessary to enhance our understanding of biocompatibility to be used to improve the in vivo lifetime of implanted medical devices and prostheses.
| Biomaterial surface-dependent neutrophil mobility
Zhou, Y., C. M. Doerschuk, et al. (2004), J Biomed Mater Res A 69(4): 611-20.
Abstract: Compromised neutrophil function in the presence of an implanted biomaterial may represent an important mechanism that allows for the development of implant-associated infections. Here, human neutrophil mobility has been investigated on a polyurethane (ChronoFlex AR), a hydrophobic surface consisting of an octadecyltrichlorosilane (OTS) self-assembled monolayer, and a glass reference material. Neutrophil mobility was quantified, based on cell movement speed and persistence time obtained from time-lapse optical microscopy, while neutrophil cytoskeletal structures and morphology were visualized using confocal microscopy and atomic force microscopy. Our results show that material surface properties affect neutrophil-surface interactions, as reflected by morphological changes, and the mobility of neutrophils stimulated by N-formylmethionyl-leucyl-phenylalanine (fMLP). In the absence of adsorbed plasma proteins, the mobility of stimulated neutrophils increased with increasing material hydrophobicity from glass, to polyurethane, to OTS. The opposite trend was observed in the presence of adsorbed plasma proteins, such that neutrophil mobility increased with decreasing material hydrophobicity. Analysis of the results showed that the mobility of fMLP-stimulated neutrophils cells was inversely related to the extent of cell spreading on the materials.
| Biomaterial surfaces
Ratner, B. D., A. B. Johnston, et al. (1987), J Biomed Mater Res 21(A1 Suppl): 59-89.
Abstract: The nature of a biomaterial surface governs the processes involved in biological response. Surface properties such as surface chemistry, surface energy, and morphology may be measured in order to understand the surface region of a biomaterial. In this article, we describe the surface characteristics of a few common biomaterials, review the techniques used to measure surface properties, and discuss the application of surface information in developing novel and improved biomaterials.
| Biomaterial with chemically engineered surface for protein immobilization
Mansur, H. S., R. L. Orefice, et al. (2005), J Mater Sci Mater Med 16(4): 333-40.
Abstract: The last 3 decades have been a revolution in the area of sol-gel-derived materials. They can be used to encapsulate biomolecules such as enzymes, antibodies, hormones, and proteins retaining their functional state. Proteins can be immobilized in many ways but it is crucial that they retain their native conformational structure and, therefore, bioactivity. Porous silica gel matrixes with modified surfaces offer unlimited possibilities to control the protein-solid interaction behavior. The bioimmobilization process on sol-gel biomaterials with chemically engineered surface has driven applications on solid-phase materials, affinity chromatography, biosensors and many others. In the present work, we have aimed to produce surface-modified silica glass materials obtained via sol-gel route to be used as solid support on drug delivery systems and as solid-phase in immunodiagnostic. The functionalization process was carried out by reacting alkoxysilanes with 5 different silane surface modifying chemical groups: tetraethoxysilane (TEOS), 3-mercaptopropyltrimethoxysilane (MPTMS) and 3-aminopropyltriethoxysilane (APTES), 3-glycidoxypropyltrimethoxysilane (GPTMS) and 3-isocyanatopropyltriethoxysilane (ICPES). The bioactivity assays were based on two main tests: (a) An in vivo bioresponse of rats with sol-gel disk implants with insulin protein incorporated. In vivo tests with adult male rats were used to verify the immobilized insulin bioactivity after implantation of different biomaterial with functionalized surfaces. All surface modified materials have presented hypoglycemic peak response associated with the insulin bioactivity. (b) The produced solid-phase sol-gel disks with protein substrates were tested through Enzyme Linked Immuno Sorbent Assay (ELISA). The immunoassay results have showed that glasses with chemically functionalized surfaces regulated the extent of bioimmobilization of protein. The amine, thiol and hydroxyl terminated porous gels have showed significant interaction with the antibody-antigen, during the coupling process. We believe that it is due to balance of forces associated with Van der Waals interaction, hydrophilic and hydrophobic forces and steric hindrance acting at the surface. Therefore, such novel biomaterial could be advantageously used in drug delivery systems and in immunoassays of diagnostic kits.
| Biomaterial-associated calcification: pathology, mechanisms, and strategies for prevention
Schoen, F. J., H. Harasaki, et al. (1988), J Biomed Mater Res 22(A1 Suppl): 11-36.
Abstract: Deposition of calcium-containing apatite mineral occurs widely in association with cardiovascular and noncardiovascular medical devices and biomaterials, is the leading cause of failure of contemporary bioprosthetic heart valves, and limits the functional lifetime of experimental (and potentially clinical) mechanical blood pumps and polymeric heart valves. Calcification of bioprosthetic tissue is primarily intrinsic, related to cuspal connective tissue cells and fragments, and collagen. In contrast, the predominant site of calcific crystals on flexing polymeric surfaces in blood pumps or valve prostheses is extrinsic, associated with adherent cells, thrombus, or pseudointima. Pathologic calcification shares key features with physiologic skeletal mineralization, including crystal initiation through the mediation of cell membranes, usually in the form of extracellular vesicles. This suggests a unified hypothesis for normal and abnormal mineralization. Several approaches are being studied experimentally for the inhibition of bioprosthetic heart valve calcification. Controlled-release diphosphonate therapy, perhaps in conjunction with an anticalcification cuspal pretreatment, appears most effective. Research objectives in biomaterial-associated calcification include (1) development of animal models, (2) determination of initial crystal nucleation events and sites, (3) elucidation of the relative roles of host, implant, and mechanical determinants, and (4) development of approaches for the inhibition of mineralization.
| Biomaterial-associated infection of gentamicin-loaded PMMA beads in orthopaedic revision surgery
Neut, D., H. van de Belt, et al. (2001), J Antimicrob Chemother 47(6): 885-91.
Abstract: In two-stage orthopaedic revision surgery, high local levels of antibiotics are achieved after removal of an infected prosthesis through temporary implantation of gentamicin-loaded beads. However, despite their antibiotic release, these beads act as a biomaterial surface to which bacteria preferentially adhere, grow and potentially develop antibiotic resistance. Gentamicin-loaded beads were retrieved from 20 patients with prosthesis-related infections. Excised tissue samples were taken for routine culture, while beads were analysed in an extensive laboratory procedure. Extensive culture procedures indicated the presence of bacteria on gentamicin-loaded beads in 18 of the 20 patients involved, while 12 of these 18 patients were considered free of infection by routine culture. Nineteen of 28 bacterial strains isolated were gentamicin resistant and cultures from three patients yielded highly gentamicin-resistant sub-populations. It is concluded that routine culture of excised tissues in orthopaedic revision surgery is inadequate to ascertain full eradication of infection, especially as infecting, antibiotic-resistant bacteria preferentially adhere to and grow on gentamicin-loaded beads. Extensive examination of the bead surfaces is proposed as a more reliable indication that infection has been eradicated.
| Biomaterial-associated infection with Candida albicans in mice
Rozalska, B., A. Ljungh, et al. (1995), Microbiol Immunol 39(7): 443-50.
Abstract: Candida yeasts are frequently isolated from patients with continuous ambulatory peritoneal dialysis peritonitis or other biomaterial-associated infections. The mouse model of candidal peritonitis was used to study the interaction of Candida cells with end-point attached heparinized polyethylene (H-PE) and with polymorphonuclear leukocytes (PMNs) or macrophages (M phi). Two Candida strains differing in cell surface hydrophobicity and in expression of fibronectin (Fn) binding were used for the study. Cells of both Candida strains adhered at higher numbers to H-PE surfaces preadsorbed with Fn or with human dialysis fluid (HDF) than to non-modified H-PE, supporting a role of Fn in mediating adhesion. C. albicans 4016 cells expressing low hydrophobicity and low binding of soluble Fn demonstrated stronger adhesion to PMNs than the more hydrophobic C. albicans 3248 yeasts, which express high binding of soluble Fn. However, C. albicans 4016 cells were more resistant to phagocytic killing and were hardly eradicated in intraperitoneally infected mice. The animals depleted in PMNs by treatment with CY were neither able to eradicate C. albicans 3248 (rapidly eliminated by normal mice) nor C. albicans 4016 yeasts (with a tendency to persist in the tissues of normal mice).
| Biomaterial-associated infection, neoplasia, and calcification. Clinicopathologic features and pathophysiologic concepts
Schoen, F. J. (1987), ASAIO Trans 33(1): 8-18.
| Biomaterial-associated persistence of Staphylococcus epidermidis in pericatheter macrophages
Boelens, J. J., J. Dankert, et al. (2000), J Infect Dis 181(4): 1337-49.
Abstract: Biomaterial surfaces may be modified to reduce bacterial adhesion. The susceptibility in mice to Staphylococcus epidermidis infection in tissue surrounding the commonly used catheter materials-silicon elastomer (SE), polyamide (PA), and their surface-modified polyvinylpyrrolidone (PVP)-grafted derivatives, SE-PVP and PA-PVP, respectively-was assessed. Abscesses developed around SE-PVP. Around SE, PA, and PA-PVP catheters, no signs of infection were observed, although mice carrying PA-PVP developed septicemia after 14-21 days. S. epidermidis was cultured from the tissue surrounding PA-PVP segments. Cells around PA-PVP segments containing large numbers of bacteria were identified as macrophages by use of immunohistochemistry and electron microscopy. This persistence of intracellular bacteria was also observed around SE-PVP, SE, and PA catheters, although to a lesser extent. The cytokine profiles around the 4 materials were different. Implanted biomaterial induces an inflammatory response favorable to the persistence of S. epidermidis. Intracellular persistence of bacteria inside macrophages may be a pivotal process in the pathogenesis of biomaterial-associated infection.
| Biomaterial-associated staphylococcal peritoneal infections in a neutropaenic mouse model
Rozalska, B. and A. Ljungh (1995), FEMS Immunol Med Microbiol 11(4): 307-19.
Abstract: Adhesion of staphylococcal cells to polyethylene with end point-attached heparin was quantified by bioluminescence. Staphylococcus epidermidis 3380 and the slime-producing S. epidermidis RP12 adhered to the highest extent, and S. lugdunensis 2342 to the least extent. Preincubation of the polymer with dialysis fluid reduced adhesion of S. epidermidis 3380 and RP12 but enhanced that of S. aureus, and preadsorption of the surface with fibronectin decreased subsequent adhesion of S. epidermidis and S. haemolyticus strains. When staphylococci were grown in the presence of a biomaterial their ability to activate peritoneal cells was decreased. The bactericidal activity was impaired, whereas ingestion of opsonized coagulase-negative staphylococci (CNS) strains was unaffected. With S. epidermidis RP12 the presence of biomaterial did not influence either phagocytosis or bactericidal effect of peritoneal cells. After intra-peritoneal challenge with staphylococcal strains, the organ uptake of S. aureus Cowan 1 was increased in normal mice whereas immunosuppressed mice died. CNS strains increased mainly in the peritoneal cavity of immunosuppressed mice. The uptake of bacteria in liver and kidneys was increased with S. epidermidis 3380, S. lugdunensis 2343 and S. schleiferi 667-88. Generally, CNS strains persisted in the peritoneal cavity of both normal and immunosuppressed mice. These data indicate that host defense mechanisms, mainly polymorphonuclear neutrophils, fail to eliminate CNS infections in the peritoneum, and that initial adhesion to an implanted biomaterial may be of lesser importance in the peritoneal cavity than in e.g. catheter-associated infections. There are strain-specific virulence factors of bacteria, and slime producing strains evade the host defense mechanisms more efficiently than non-slime producing strains.
| Biomaterial-associated thrombosis: roles of coagulation factors, complement, platelets and leukocytes
Gorbet, M. B. and M. V. Sefton (2004), Biomaterials 25(26): 5681-703.
Abstract: Our failure to produce truly non-thrombogenic materials may reflect a failure to fully understand the mechanisms of biomaterial-associated thrombosis. The community has focused on minimizing coagulation or minimizing platelet adhesion and activation. We have infrequently considered the interactions between the two although we are generally familiar with these interactions. However, we have rarely considered in the context of biomaterial-associated thrombosis the other major players in blood: complement and leukocytes. Biomaterials are known agonists of complement and leukocyte activation, but this is frequently studied only in the context of inflammation. For us, thrombosis is a special case of inflammation. Here we summarize current perspectives on all four of these components in thrombosis and with biomaterials and cardiovascular devices. We also briefly highlight a few features of biomaterial-associated thrombosis that are not often considered in the biomaterials literature: The importance of tissue factor and the extrinsic coagulation system. Complement activation as a prelude to platelet activation and its role in thrombosis. The role of leukocytes in thrombin formation. The differing time scales of these contributions.
| Biomaterial-centered infection: microbial adhesion versus tissue integration
Gristina, A. G. (1987), Science 237(4822): 1588-95.
Abstract: Biomaterials are being used with increasing frequency for tissue substitution. Complex devices such as total joint replacements and the total artificial heart represent combinations of polymers and metal alloys for system and organ replacement. The major barriers to the extended use of these devices are the possibility of bacterial adhesion to biomaterials, which causes biomaterial-centered infection, and the lack of successful tissue integration or compatibility with biomaterial surfaces. Interactions of biomaterials with bacteria and tissue cells are directed not only by specific receptors and outer membrane molecules on the cell surface, but also by the atomic geometry and electronic state of the biomaterial surface. An understanding of these mechanisms is important to all fields of medicine and is derived from and relevant to studies in microbiology, biochemistry, and physics. Modifications to biomaterial surfaces at an atomic level will allow the programming of cell-to-substratum events, thereby diminishing infection by enhancing tissue compatibility or integration, or by directly inhibiting bacterial adhesion.
| Biomaterial-centered infection: microbial adhesion versus tissue integration. 1987
Gristina, A. (2004), Clin Orthop Relat Res(427): 4-12.
| Biomaterial-centered sepsis and the total artificial heart. Microbial adhesion vs tissue integration
Gristina, A. G., J. J. Dobbins, et al. (1988), Jama 259(6): 870-4.
Abstract: The principal barrier to the extended use of the total artificial heart is infection that is centered on the biomaterial constituting the prosthetic device and exacerbated by the surrounding damaged tissue. Ultrastructural studies of total artificial hearts removed from two patients indicate a failure of true tissue integration and diffuse, adhesive bacterial colonization of biomaterial surfaces. Biomaterials are, in part, susceptible to infection because, at the present state of the art, they are usually not well integrated with host tissue or, if hemodynamic, not optimally biocompatible or antiadhesive.
| Biomaterial-dependent blood activation during simulated extracorporeal circulation: a study of heparin-coated and uncoated circuits
Borowiec, J. W., P. Venge, et al. (1997), Thorac Cardiovasc Surg 45(6): 295-301.
Abstract: OBJECTIVE: Blood activation during extracorporeal circulation is associated with morbidity and mortality in cardiac surgery. This activation can be diminished by usage of heparin-coated circuits. Nitric oxide has also been reported to influence humoral and cellular components of blood. This study was performed to determine biomaterial-dependent part of blood activation. DESIGN: Fresh, whole human blood mixed with Ringer's solution was circulated through a heart-lung machine for two and half hours. Five circuits were heparin-coated (group HC), whilst five other circuits were uncoated (group NC). During the last half hour NO was added to the oxygen/air mixture. METHODS: Blood activation was estimated by measuring following parameters: interluekin 6, complement activation products C3a and terminal complement complex, and oxygen free radicals (OFR) production capacity, which was determined using chemiluminescence enhanced by serum opsonized zymosan (SOZ) and phorbol myristate acetate (PMA). Granulocyte activation was measured as release of myeloperoxidase (MPO) and human neutrophil lipocalin (HNL). RESULTS: OFR in granulocyte suspension stimulated by SOZ and PMA were significantly lower in the NC group, mostly later during ECC. Similarly, lower neutrophil and monocyte counts were observed in this group. NO increased superoxide production in the whole blood in heparin-coated circuits, but did not change OFR in isolated granulocytes. MPO was also affected by heparin-coating. NO supply seemed to increase release of MPO and HNL. It is concluded that heparin-coating contributed to reduction of biomaterial-dependent blood activation. An addition of NO at late stage of ECC tended to influence this activation.
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