Abstract 1327: Endovascular Stents are a Potential New Intra-Arterial Delivery Platform for Pro-Arteriogenic Growth Factors
Background: The stimulation of collateral artery growth (arteriogenesis) using cytokines is a potential treatment option for patients suffering from vascular occlusive diseases. Several cytokines have been identified that stimulate the growth of collateral arteries and capillaries. However, the lack of a suitable delivery platform for chronic intra-arterial application of pro-arteriogenic cytokines has hampered the clinical implementation of this promising therapeutic strategy. In the present study we determined the efficacy of a newly developed stent, releasing the pro-arteriogenic cytokine transforming growth factor beta1, to stimulate collateral artery growth in the peripheral circulation of the rabbit.
Methods and Results: A TGF-beta loaded polymer coating, based on poly(D,L-lactide), was applied on 15 mm coronary cobalt-chrome alloy stents. A dip-coating method was used, obtaining a total load of about 9μg TGF-beta. In-vitro testing confirmed elution of about 2.5 μg active TGF-beta over the treatment period of seven days. 45 rabbits underwent implantation of bare-metal-stents (BMS), polymer-only-coated stents (PCS) or polymer-coated TGF-beta eluting stents (TGF) in the iliac artery and subsequent femoral artery ligation (n=15/group). After seven days, microsphere-based perfusion measurements revealed a significant increase in collateral conductance following TGF-beta1-stent implantation compared to the control groups ([ml/min/100mmHg] BMS: 47.8±2.5; PDLLA: 44.1±3.9; TGF: 91.3±32.6.0, P=0.004 for TGF vs. BMS, P=0.002 for TGF vs. PDLLA). Histological analysis of collateral arteries verified a significantly increased proliferation of vascular smooth muscle cells in the TGF-treated group (%Ki67+ VSMC: BMS: 18.9±1.3; PDLLA: 18.4±2.3; TGF: 27.5±8.0). At seven days, no significant difference in in-stent neointima formation was observed (neointima area [mm2]: BMS: 0.30±0.10; PDLLA: 0.28±0.11; TGF: 0.30±0.13).
Conclusion: We first describe the use of a cytokine-releasing stent to stimulate collateral artery growth. These results show that intra arterial cytokine-releasing devices may serve as a novel platform for the delivery of compounds affecting biological processes downstream to the site of implantation.