Mechanism of failure of biocompatible‐treated surfaces

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Abstract
In recent years, significant advances have been made in treating surfaces to enhance their biocompatibility. This has generally involved the chemical attachment of very thin molecular coatings to a substrate. Because failure of coated surfaces occurs often, an investigation of the stability of one such molecular coating was undertaken. The specific system being studied is a polytetrafluoroethylene polymer (Teflon) with organic macromolecules of heparin ionically bonded to the polymer through use of an intermediate bonding agent. Polymers properly treated in this fashion have been shown to have excellent antithrombogenic properties. To investigate the molecular stability of the heparin coating, the surface heparin concentration of a properly coated sample was reduced by using three different methods: exposure of bonding agent to a suitable solvent; mechanical flexing; and ultrasonic vibration in saline solution. Changes in heparin distribution, average concentration, and biocompatibility were measured. Observation of the heparin distribution was accomplished by decorating the surface with vapor‐deposited gold nuclei, stripping, and then examining the replica in a transmission electron microscope. Comparisons of the nucleation replicas show definite differences in the gold nuclei patterns for heparin, untreated Teflon, and the intermediate bonding agent‐covered areas. Average heparin concentrations were measured separately by radioisotope labeling. Biocompatibility was determined by exposing the samples to platelet‐rich plasma in closed flow chambers and subsequent examination for microthrombi on the scanning electron microscope. These experiments have shown that the original molecular coat does not completely cover the surface even though radioisotope labeling indicates enough molecules present to form a 5000–10,000 Å covering. The heparin does cover more than 95% of the surface; however, uncoated areas less than 2 μ in diameter are dispersed throughout. In all three methods of surface heparin removal, the heparin was removed in association with its intermediate bonding agent. Rather than the molecular layers gradually decreasing in thickness, certain areas become void of heparin while adjacent areas are unaffected. This results in the formation of heparin islands as the concentration is further reduced. The treated surfaces can lose their biocompatibility whenever heparin‐denuded areas greater than 20 μ in diameter are present. Usually, this will occur when the heparin‐coated surface area drops below 30%. Such a surface theoretically has sufficient heparin for a 500 Å thick continuous molecular coat. Definite differences exist in the heparin distribution pattern resulting from the different techniques used for degrading the surface. Mechanical flexing results in highly selective areas of heparin loss, ultrasonic vibration results in more continuous hepain loss, and solution exposure results in random areas of heparin loss. A molecular coated surface may fail prematurely, even when enough molecules are present to form a multilayer continuous coat, due to the presence or creation of microscopic molecular denuded areas. The creation of these denuded areas on a surface is dependent upon the type of degradation the surface undergoes.