Dual-Drug Stent with Sirolimus and WKYMVm Promotes Endothelialization and Limits Hyperplasia

Conventional drug-eluting stents suppress neointimal hyperplasia but delay re-endothelialization, raising long-term safety concerns. This study developed and evaluated a sirolimus-WKYMVm eluting stent (S-WES) to simultaneously promote re-endothelialization and suppress neointimal hyperplasia.

Sirolimus-eluting stents (SES), WKYMVm-eluting stents (WES), and S-WES were fabricated using electrospray. Surface morphology was characterized via scanning electron microscopy (SEM), and in vitro drug-release kinetics were determined using high-performance liquid chromatography. Biological efficacy was assessed using human umbilical vein endothelial cell (HUVEC) and smooth muscle cell (SMC) assays. In vivo performance was evaluated over 4 weeks, followed by optical coherence tomography (OCT) and histopathological analysis.

SEM analysis showed that S-WES had a uniform, crack-free polymer coating. Each stent was consistently loaded with sirolimus (105.15 ± 25.54 μg) and WKYMVm (1.07 ± 0.18 μg), yielding a dual drug-release profile. WKYMVm was almost completely released within 7 days, whereas sirolimus showed sustained release (day 1: 22.43 ± 5.32%, day 28: 94.38 ± 4.11%). In vitro assays showed that sirolimus suppressed SMC migration and HUVEC proliferation, while WKYMVm significantly enhanced HUVEC proliferation. In vivo OCT revealed reduced neointimal hyperplasia in the S-WES group (29.64 ± 8.66 μm²) compared with SES (34.65 ± 7.50 μm²; p = 0.041). Histopathology and immunohistology showed reduced stenosis ratio (28.39 ± 6.84%), decreased α-SMA expression, and increased VE-cadherin, CD31-positive endothelial coverage in the S-WES group.

The sirolimus-WKYMVm dual-drug stent enhances re-endothelialization and inhibits neointimal hyperplasia, thereby offering a promising strategy for improving the efficacy and long-term safety of cardiovascular stents.