BACTERIAL COLONIZATION OF SURGICAL BIOMATERIALS

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Progress in the development and use of biomaterials and artificial organs has been delayed by the serious complications of infection and exaggerated host inflammatory responses. Biomaterial implants are surrounded by an immuno-incompetent, fibro-inflammatory, integration deficient zone which is susceptible to infection due to the adherence of S. epidermidis and other bacteria, and because of host cellular and humoral immune perturbation. This proposal is directed to the investigation and moderation of those crucial problems. Our objectives are to further characterize bacterial adherence mechanisms and the cellular immune dysfunction components of biomaterial tissue interface sepsis using an integrative investigative approach to causal and therapeutic mechanisms defined in an animal model. Our objective in AIM 1 will test the effectiveness in vitro and in vivo of antibodies against bacterial adhesins in blocking colonization of biomaterials by clinically relevant strains of Staphlococcus epidermidis. These studies will indicate if the immunization of at risk groups is an effective strategy. AIM 2 will examine the hypothesis that macrophages will preserve their oxidative and killing capacity if binding to biomaterials is minimized by surface modification. AIM 3 will test the effectiveness of a novel in vivo mechanism to prime macrophages to express augmented killing capacity in resisting and clearing biomaterial-centered sepsis. AIM 4 will relate the role of surface microstructure, composition and oxide ultrastructure of a systematically varied single alloy system Ti6A14V to site-specific patterns of bacterial adhesion and protein adsorption. This last objective will include antibody immunogold studies of the adsorption patterns of proteins of in vivo acquired conditioning films and relate these findings to data derived from high resolution surface analysis and bacterial adhesion. We have developed and tested an effective animal model which will be utilized to examine the ability of antiadhesin antibodies to prevent and clear biomaterial infection (AIM 1). The macrophage immune augmentation technique (AIM 3) and the biomaterial coating and conditioning studies (AIMS 2,4) will also utilize the animal model.