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A cage implant system was utilized to quantitatively and qualitatively characterize in vivo leukocyte interactions with cast Biomer. Scanning electron microscopy (SEM) in conjunction with cytochemical staining procedures were used to investigate the cellular events at the leukocyte/Biomer interface as well as in the inflammatory exudate over a 21-day implantation period. SEM was used to characterize leukocyte morphology on the Biomer surface and the cytochemical stains were used to differentially count leukocytes and to demonstrate intracellular alkaline and acid phosphatase activity. The results showed that the population density of leukocytes on the Biomer surface diminished with implantation time. The population density of multinucleated foreign body giant cells remained constant with time, while the numbers of nuclei per giant cell increased. The differential analysis revealed that macrophages preferentially adhered to the Biomer surface compared to other leukocytes in the exudate. The phagocytic capability of all adherent leukocytes, including giant cells, decreased with time and this corresponded to changes in leukocyte morphology observed with SEM.

Of the many factors determining host biocompatibility responses to implanted biomedical polymers, the cellular interactions at the tissue/material interface have been recognized to be some of the most important. The present study has combined results both from an in vitro cell culture system and from an in vivo animal model to examine this host response. In vitro results suggest that a variety of polymer materials can differentially activate human monocytes to produce a protein(s) having different biological activities. The polymers tested induce the production of the regulatory inflammatory protein interleukin 1 as well as a factor that enhances fibroblast proliferation and collagen synthesis. The observed activities of these factors appear to be related but not identical, and are dependent upon the specific polymer. Evaluation of exudate and tissue responses to these same polymer materials in an in vivo model are also presented. Both in vitro and in vivo results support the hypothesis that monocyte/macrophage activation with subsequent synthesis of regulatory factors such as interleukin 1 plays a significant role in determining the host response to biomedical polymer implants.

Complement-associated leukocyte adhesion appears to be a consistent in vitro and in vivo finding for many types of polymers; however, very little work has been done on the interaction of leukocytes with vascular graft materials. An in vitro perfusion system was used to study complement and leukocyte activation associated with the following vascular graft materials when tested with human blood: expanded polytetrafluoroethylene (ePTFE), crimped Dacron Bionit (DB) and preclotted Dacron Bionit. A decrease in the total leukocyte concentration with perfusion time was seen for all materials tested, and paralleled leukocyte adhesion to the graft surface as observed by scanning electron microscopy. The most dramatic decrease in leukocyte concentration was observed for the interaction of heparinized whole blood with Dacron. This was due to a selective decrease in neutrophils and monocytes, and was correlated with an increase in both leukocyte adhesiveness and complement activation, as measured by C5a elevation. Inhibiting complement activation by use of the anticoagulant, sodium citrate, curtailed Dacron-induced leukocyte adhesion. Little leukocyte or complement activation was observed for ePTFE or the silicone rubber control regardless of the anticoagulant used.