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Biomedical subjects

S L Cooper

Publications and source records attributed to S L Cooper.

At least 127 records · Page 7Linked to original sources

Studies on the cellular basis of atherosclerosis: the effects of atherosclerosis risk factors on platelets and the vascular endothelium.

Thrombosis is a well-recognized complication of atherosclerosis and may be a factor in initial lesion formation. Experimental endothelial cell injury results in activation of the coagulation mechanism and therefore may be a critical aspect of the pathogenesis of occlusive vascular disease. If this is so, then risk factors for atherosclerosis should affect the endothelium either by causing cell injury, inhibiting repair mechanisms, or altering its thromboresistant properties. To test this, we studied the effect of several risk factors on endothelial cell behavior in vitro. Since the smooth muscle cell is the major cellular component of human atherosclerotic plaque and since a primary smooth muscle cell lesion is suggested by the clonal nature of human plaque, we also studied the effect of risk factors on arterial smooth muscle behavior. We have found that homocysteine directly injures human endothelium, which may account for the premature arterial disease in homocystinuria. Serum from patients with familial hypercholesterolemia inhibits the critical function of endothelial cell migration, as well as arterial smooth muscle cell migration. Moderate hypoxia has no effect on endothelial cell or smooth muscle cell viability, proliferation, or migration. Platelet factors are shown to affect human smooth muscle cell proliferation and both endothelial cell and smooth muscle cell migration. Preliminary study of platelet activation in diabetes with retinopathy suggests a relation to glucose control, but might reflect underlying vessel disease rather than direct platelet effect.

Arteriosclerosis↗

Cast vs extruded Biomer for biomedical applications.

The properties of solution grade and extrusion grade Biomer have been investigated and compared. In vivo blood compatibility studies using arteriovenous (AV) shunts of the cast and extruded materials show that extruded Biomer is more thromboresistant than solution cast Biomer. This has important implications for long-term implantation studies, since solution cast Biomer is used in artificial hearts. This study also indicates that extruded Biomer, dissolved in DMA and then solution cast, is more thromboresistant than cast solution grade Biomer. Surface studies using ESCA indicate a correlation between thromboresistance and surface soft segment concentration.

Animals↗

Transient in vivo protein adsorption onto polymeric biomaterials.

The adsorption of albumin, gamma-globulin, and fibrinogen was measured on three ex vivo polymeric shunt surfaces [polyvinyl chloride (PVC), Silastic, and segmented polyether urethane (Biomer)] exposed to flowing heparinized, canine blood in vivo. Small amounts of radiolabeled proteins were infused into anesthetized mongrel dogs and the deposition of radioactivity on the walls of femoral arteriovenous shunts was followed with time for two hours following initial blood-polymer contact. Previously, transient in vivo platelet and fibrin deposition onto PVC, Silastic, and Biomer was measured by a similar technique in the absence of anticoagulant. A time-dependent phase of thrombus deposition followed by thromboembolism was observed on the PVC and Silastic shunt surfaces but not on the Biomer surface. In the studies reported here on PVC and Silastic, fibrinogen adsorption was found to predominate initially, though it subsequently desorbed somewhat and was replaced by albumin and gamma-globulin. On Biomer, the adsorption of all three proteins increased with time following initial blood contact and fibrinogen was less prominent initially. The PVC surface was found to become passivated with respect to further thrombogenesis after 60-min exposure to flowing blood, at which time a higher fraction of albumin was present on the surface compared to that at earlier blood contact times. These results indicate that rearrangement of adsorbed protein species occurs with time on polymer surfaces exposed to flowing blood in vivo. Early and predominant fibrinogen adsorption appears to be an important factor in the thrombogenic and embolic events observed on the PVC and Silastic shunt surfaces in vivo.

Adsorption↗

Platelet adhesion and contact activation time tests on HEMA coated cellulose acetate membranes.

Surface modification of cellulose acetate dialysis membranes was carried out by 60Co radiation induced graft copolymerization of the hydrogel, hydroxyethyl methacrylate (HEMA). The degree of grafting was controlled by varying the HEMA monomer concentration in the grafting solution and the radiation dose. A continuous flow platelet adhesion test was designed which allows testing under conditions more closely approximating hemodialysis than other small scale in vitro tests. Platelet adhesion on treated membranes fell substantially with increasing surface HEMA concentration. The presence of HEMA on the membrane surface did not affect the membrane activated clotting times significantly.

Acrylates↗

A canine ex vivo series shunt for evaluating thrombus deposition on polymer surfaces.

A new acute canine ex vivo femoral A-V series shunt experiment is described. Platelet and fibrinogen deposition on a series of up to ten different polymers may be tested in the same nonanticoagulated animal. The method reduces the time and expense associated with animal testing, and also allows for the simultaneous monitoring of platelet and fibrinogen deposition on a number of polymer surfaces. The series shunt technique was used to examine platelet and fibrinogen deposition on polyethylene, Silastic, polyvinylchloride, and oxidized polyethylene surfaces. Following an initial period of minimal deposition, platelet deposition increased dramatically to a peak by about 15-20 min of blood contact on all surfaces studied. The amount of adsorbed fibrinogen fell from initial levels to a minimum at about 5-10 min of blood contact and then increased to a peak at about the same time as observed for the platelet response. Oxidized polyethylene was the most thrombogenic surface studied, followed by polyethylene, polyvinylchloride, and Silastic. Peak platelet and fibrinogen levels were found to be inversely related to flow rate over the range studied. In this experiment it appears that the interaction of blood components with a foreign surface in vivo or ex vivo is localized to the interface with the flowing blood. Within experimental errors, no effect of segment position or any downstream effects were observed. These results suggest that a series shunt may be used to investigate the short-term interactions of blood with a number of test surfaces.

Adenosine Diphosphate↗

The measurement of contact angles on circular tubing surfaces using the captive bubble technique.

Circular tubings are used extensively in biomedical implants and devices. It is desirable to determine contact angles on the inner or outer surfaces of such tubing in its final fabricated form. In this study, a technique for the measurement of contact angles on tubing surfaces in an aqueous environment is reported. This has particular applications to biomaterials research, where polymer tubings contact the biologic environment. In this technique, air or octane captive bubble dimensions can be measured, and an underwater contact angle calculated from these dimensions. The validity of the technique was experimentally confirmed using Solution Grade Biomer and NIH standard polyethylene surfaces.

Air↗

Acute surface-induced thrombosis in the canine ex vivo model: importance of protein composition of the initial monolayer and platelet activation.

The initial events occurring at the blood-polymer interface were examined using a canine ex vivo arteriovenous shunt model. Thrombogenic (fibrinogen) and nonthrombogenic (albumin) proteins were preadsorbed on poly(vinyl chloride), polyethylene, and silicone rubber shunt surfaces, and the blood responses were analyzed using the platelet deposition profile as an indicator of surface thrombogenicity. The distributions of preadsorbed protein molecules on the various polymer surfaces were studied using an immunogold bead (colloidal gold particles coated with antibodies) staining technique and shown to be homogeneous. A sequential protein adsorption technique was developed to probe the nature of competitive protein adsorption and to observe the effect of surface protein concentration on thrombogenicity. The thrombogenicity of a surface was determined by the composition of the initial protein layer rather than the total concentration of protein on the polymer surfaces. The composition of this layer determines the extent of platelet activation and the adhesive strength between platelets and the polymer surface.

Adsorption↗

Neutrophil adhesion on phosphorylcholine-containing polyurethanes.

Polyurethanes have been synthesized using glycerophosphorylcholine (GPC) as a chain extender. By altering the ratio of GPC to butanediol (BD), a series of polymers was obtained composed of different contents of phosphorylcholine. Bulk and surface characterization of the polymers was carried out. Differential scanning calorimetry and dynamic mechanical analysis showed that the polymer with the highest phosphorylcholine content (PU-GPC-20) had the lowest soft segment Tg and the highest tensile strength and Young's modulus among the polymers studied. This is due to the high degree of microphase separation in PU-GPC-20 as a result of by ionic aggregation and hydrogen bonding from the zwitterionic phosphorylcholine moiety. PU-GPC-20 contained approximately 20 wt%, of glycerophosphorylcholine. Dynamic contact angle analysis showed that these polymers, especially the ones with high phosphorylcholine content, rearranged themselves to minimize their interfacial tension upon contacting an aqueous environment. Under shear rates of from 20 to 120 s(-1), neutrophils did not adhere to PU-GPC-20. Under similar conditions neutrophil adhesion was observed only at 20 s(-1) on PU-GPC-10, PU-GPC-5 and on the control polyurethane (PU-base). Cell spreading was observed on the control polyurethane but not on any of the other surfaces. The incorporation of phosphorylcholine into the polyurethane backbone effectively reduced neutrophil adhesion and thus potentially could result in lower inflammatory and foreign body responses.

Absorption↗

Bacterial adhesion on polyurethane surfaces conditioned with thrombus components.

Thrombosis and infection are two major complications associated with cardiovascular devices such as ventricular assist devices, total artificial hearts, vascular grafts, and catheters. When blood contacts an artificial biomaterial, protein deposition occurs, as do activation of the blood coagulation cascade, platelet adhesion, activation, and aggregation, all of which lead to thrombus formation. An increased incidence of bacterial infection also has been seen clinically with indwelling biomaterial devices. Some evidence suggests a possible association between thrombosis and infection, in that adherent bacteria may provide a nidus for thrombus formation, or adherent thrombi composed of platelets and fibrin may form sheltered sites for bacterial adhesion. In the current study, the authors examined Staphylococcus aureus adhesion to sulfonated, aminated, and phosphonated polyurethane surfaces that had been pre-adsorbed with solutions of increasing complexity, in an effort to approach and simulate clot formation on the surface. These solutions included various combinations of fibrinogen, albumin, plasma, thrombin, and isolated platelets. Bacterial adhesion was observed in a radial flow chamber mounted on the motorized stage of a video microscopy system, with image processing software used to perform automated data collection and image analysis. Scanning electron microscopy also was used to visualize cross-linked fibrin and bacterial adhesion on these surfaces. Bacterial adhesion was found to be lowest on the phosphonated polyurethane. The presence of fibrin or isolated platelets significantly increased bacterial adhesion compared to surfaces pre-adsorbed with albumin.

Bacterial Adhesion↗

The effect of surface hydrophilicity on biomaterial-leukocyte interactions.

Leukocyte adhesion onto a series of polyetherurethanes containing various ratios of polyethylene oxide (PEO) to polytetramethylene oxide (PTMO) in the soft segment was evaluated using an in vitro series shunt. The deposition of polymorphonuclear (PMN) and mononuclear (MN) leukocytes was measured quantitatively using labelling techniques. Results showed that H/H-1, the most hydrophobic surface, adsorbed higher amounts of PMN leukocytes. It was also observed that for most materials the number of PMN and MN leukocytes deposited reached a plateau within 15 minutes. Unlike MN adherence, the presence of plasma proteins increased the number of PMN leukocytes deposited on the materials.

Biocompatible Materials↗