DOES IMPLANTATION SITE OF DRUG-ELUTING POLYMERS MATTER: SUBCUTANEOUS vs. AORTIC?

Objectives: Drug-eluting degradable polymers represent a new direction in vascular surgery. Subcutaneous implantation in rats of vascular prostheses is a rapid and cost-effective screening model to assess the drug-elution effect and could to some extent be extrapolated to forecast results for vascular implantation. We therefore assessed the biologic and histologic response according to the implantation site. Materials & Methods: Polycaprolactone(PCL), paclitaxel-loaded PCL(PCL-PTX) and dexamethasone-loaded PCL(PCL-DXM) grafts were implanted subcutaneously(n=60) and in an infrarenal abdominal aortic replacement model(n=28) in rats for 1,3 and 12 weeks. At conclusion of the study histological analysis was performed in all groups and models. Results: Cellular graft invasion was analyzed by morphometry in the subcutaneous and aortic group revealing time differences of infiltration between PCL, PCL-PTX and PCL-DXM groups in both models. Cell infiltration was continuously increasing with time in the aortic model compared to the subcutaneous model(41% vs. 28% at 12 weeks). Morphological cell counting revealed major differences in fibroblast, macrophage and giant cell graft colonisation with time. Macrophages and giant cells increased more in the aortic compared to the subcutaneous model after 3 weeks but decreased in the drug-eluting groups. Other major findings were observed only in the aortic replacement such as extracellular matrix deposition and neo-angiogenesis. Conclusions: The subcutaneous polymer implant model can be used for screening, especially when drug-eluting effects are studied. However major histological differences are observed in cell type reaction and depth of cell penetration compared to the aortic replacement model. Thus our results demonstrate that no extrapolations should be made from a subcutaneous screening to a vascular implantation model.