Influence of test protocol in determining the blood response to model polymers.

A multi-parametric, multi-center evaluation of three polymers was performed measuring their response to blood contact. The purpose of this study was to pinpoint differences in tests performed for assessing "basic" hemocompatibility on identical materials at different centers and attempt to rationalize. Assays for platelet adhesion, activation, aggregability and activation of the coagulation system in addition to an ex vivo patency assay were performed at four centers across Europe, using protocols favored by each center for determining the blood-contacting performance of a biomaterial. Three polymers were chosen for their expected blood response spanning the range of undesirable to desirable: ethylenevinylacetate (EVA), polyvinylchloride (PVC) and PVC modified with polyethylene oxide (PEO). The assays were ranked in terms of their efficacy compared to cost and simplicity. A correlation between assays was calculated, indicating the ability of one test to correctly determine the blood response compared to another. Some assays were unable to distinguish between materials, but of the assays which could, the materials were ranked in the following order: EVA; PVC; PVC-PEO, EVA producing the most undesirable response. It is concluded that many commonly used assays for determining hemocompatibility are inappropriate, but there are simple and reliable test methods available which correlate well with the more sophisticated protocols.

A new in vitro thrombogenicity test for medical tubes.

Basic information on the affected coagulation behaviour of healthy human blood passing foreign artificial surfaces is of immense importance for a safe clinical therapy. An in vitro screening method is presented which tests the thrombogenicity of medical tubes, applying the clinically already established resonance thrombography (RTG). Several medical tubes with various types and contents of plasticizers are tested and compared with materials free of additives. The effect of the release of ingredients is indicated by this procedures, as well as the influence of a sterilizing treatment with gamma-radiation on the physical surface properties, such as smoothness. In all cases, the modified RTG method proves its suitability and sensitivity. In addition, this method allows accurate adjustment of the extrusion parameters for tube manufacturers.

Biostability of polyurethanes.

Aside from the medical requirements a material has to fulfill to qualify as biocompatible, for the bioengineer, who is involved in the design, construction and fabrication of prosthetic devices, the mechanical, physical and chemical properties of the material as well as its possible manufacturing procedures and, last but not least, its biostability are of the same importance. In the very aggressive biological environment, the material should behave inertly, showing no surface erosions, molecular chain disruptions, uptake of low molecular weight biological materials, local chemical imbalances, tendency to calcification or negative changes of mechanical properties. With regard to this aspect, different polyurethanes have been evaluated in-vitro and in-vivo as basic materials and already fabricated devices (blood pumps and heart valves). The comparison of the results stresses the necessity of further efforts to achieve a standardized test protocol for the prove of the biostability of polymers, containing appropriate, well-defined in-vitro and in-vivo test methods to establish the necessary data basa for the materials' clinical approval.

A material (PUPA) presenting both the properties of polyurethanes and the capacity of adsorbing a high quantity of heparin.

Polyurethanes are widely used for biomedical applications, but there is still a constant search for improved blood-compatible materials. We studied a material (PUPA) obtained by the interconnection between a poly(amido-amine), N2LL, capable of forming stable complexes with heparin and a commercial polyurethane, Pellethane 2363-80AE, using hexamethylenediisocyanate as the crosslinking agent. The amount of absorbed heparin (evaluated by biological tests) was generally much higher than that found on the poly(amido-amine) surface-grafted polyurethane.

Blood-material interaction, ex-vivo test for the initial events.

The different tubes affected the tested parameters in different ways. The fibrin and platelet amplitudes are the most sensitive parameters of the RTG-method. A rough surface alterates preferably the platelet activity in the first two milliliters. After about one minute of blood material interaction the amplitudes of fibrin and thrombocytes of all materials have reached the level of the reference blood. The tube with the lowest thrombogenic response to the blood is the polyurethane tube followed by polypropylene, Silastic, polyurethane with the rough surface and finally PVC. In this ex-vivo method the materials are tested under dynamic and nearly physiological conditions. Only one animal is needed for all experiments. No anaesthesia, no anticoagulants are required. The experimental effort and the costs are low. The results are well reproducible although the blood flow might vary slightly. Finally the test results are immediately available.

Transvenous double-balloon occlusion of the persistent ductus arteriosus: an experimental study.

A new method of transvenous catheter closure has been developed for closure of a persistent ductus arteriosus (PDA), especially in infants and children. The device consists of a 5F or 6F triple-lumen catheter which carries a detachable silicone double-balloon at the tip. After expanding the distal positioning balloon, the proximal occlusion balloon is placed in the PDA and filled to the required size with radiopaque silicone. As the silicone cures inside the balloon, a solid plug occludes the PDA after it is detached from the catheter. In 21 beagles a short segment of subclavian artery was interposed between the main pulmonary artery and the descending aorta, simulating a PDA. The procedure was tested on these models and proved to be suitable. Within one month the plug was covered with fibrous tissue at the pulmonary and aortic ends, thus ensuring permanent occlusion. The long-term follow-up extended for up to two years and confirmed the biocompatibility of the silicone plug.

A new in-vitro thrombogenicity test: resonance-thrombography in comparison with material-thrombelastography.

The RTG method is a new in-vitro method to test thrombogenicity of biomaterials. It proves to be faster, more reliable and more comfortable in handling than all other in-vitro tests existing nowadays. Furthermore, the RTG method yields more differentiated and revealing results about thrombogenicity of artificial materials.