Local Stent-Based Release of Transforming Growth Factor-β1 Limits Arterial In-Stent Restenosis

The long-term success of intra-arterial stenting remains limited by in-stent restenosis (ISR). Transforming growth factor-β1 (TGF-β1) can inhibit smooth muscle cell (SMC) proliferation and migration and convert SMCs into extracellular matrix (ECM)-synthesizing cells. Here, we evaluate the effects of stent-based delivery of TGF-β1 on ISR in a rabbit model. Channeled stents loaded with TGF-β1 or control microspheres were deployed in rabbit aortas. Stented aortas were harvested at 7 and 28 d and evaluated for Ki-67-positive cells, collagenous ECM production, and intima-to-media (I/M) ratio. At 7 d, the TGF-β1 group exhibited fewer Ki-67-positive cells were found for the TGF-β1 group (17.87 ± 2.18 cells per mm(2)) relative to control (25.07 ± 2.65 cells per mm(2), p = 0.04), but increased collagen content (31.4 ± 2.5 percentage area) compared with control (29.3 ± 1.2 percentage area, p = 0.019). The I/M ratio in the TGF-β1 group was reduced by 50% and 9.1% versus control at 7 d (0.13 ± 0.02 vs. 0.26 ± 0.02, p = 0.0001) and 28 d (1.80 ± 0.05 vs. 1.98 ± 0.08, p = 0.0038), respectively. Stent-based controlled release of TGF-β1 limits ISR and is associated with inhibition of SMC proliferation but an increase in ECM production.