In-
stent restenosis (ISR) and late
stent thrombosis are the major complications associated with the use of
metal stents and
drug eluting stents respectively. Our lab previously investigated the use of
peptide CD47 in improving biocompatibility of bare
metal stents in a rat carotid
stent model and our results demonstrated a significant reduction in platelet deposition and ISR. However, this study did not characterize the stability of the pepCD47 on
metal surfaces post storage, sterilization and deployment. Thus, the objective of the present study was 1) to test the stability of the
peptide post - storage, sterilization, exposure to shear and mechanical stress and 2) to begin to expand our current knowledge of pepCD47 coated
metal surfaces into the preclinical large animal rabbit model. Our results show that the maximum immobilization density of pepCD47 on
metal surfaces is approximately 350 ng/cm2. 100% of the pepCD47 was retained on the
metal surface post 24 weeks of storage at 4 °C, exposure to physiological shear stress, and mechanical stress of
stent expansion. The bioactivity of the pepCD47 was found to be intact post 24 weeks of storage and
ethylene oxide sterilization. Finally our ex vivo studies demonstrated that compared to bare
metal the rabbit pepCD47 coated surfaces showed - 45% reduced platelet adhesion,
a 10-fold decrease in platelet activation, and 93% endothelial cell retention. Thus, our data suggests that pepCD47 coating on
metal surfaces is stable and rabbit pepCD47 shows promising preliminary results in preventing
thrombosis and not inhibiting the growth of endothelial cells. STATEMENT OF SIGNIFICANCE: Biocompatibility of bare
metal stents is a major challenge owing to the significantly high rates of in-
stent restenosis. Previously we demonstrated that
peptide CD47 functionalization improves the biocompatibility of bare
metal stents in rat model. A similar trend was observed in our ex vivo studies where rabbit blood was perfused over the rabbit pepCD47 functionalized surfaces. These results provide valuable proof of concept data for future in vivo rabbit model studies. In addition, we investigated stability of the pepCD47 on
metal surface and observed that pepCD47 coating is stable over time and resistant to industrially relevant pragmatic challenges.