Intimal hyperplasia (IH) at vascular anastomosis sites arises from endothelial injury, thrombin activation, and the subsequent proliferation and phenotypic modulation of vascular smooth muscle cells (VSMCs). Existing clinically used systemic pharmacologic regimens (e.g., antiplatelet/anticoagulant therapy) and reported local material-based strategies in the literature (e.g., drug-eluting sutures, hydrogels, or coatings) largely rely on drug release, which can result in burst kinetics, finite duration, and off-target/systemic exposure. We developed a covalently immobilized, non-releasing biointerface in which mitomycin C (MMC) is stably anchored onto polypropylene sutures via low-pressure, non-thermal acetic-acid plasma (AAP) activation. AAP functionalization introduced reactive oxygen-containing groups on polypropylene, enabling amide-bond immobilization of MMC while preserving suture mechanics. Anchored MMC exhibited potent contact-mediated regulation of VSMC fate, reducing metabolic activity to 81% of control, suppressing G2/M progression, and inducing a dominant sub-G1 apoptotic population (66.3%), consistent with MMC-induced DNA crosslinking, p21 upregulation, and cyclin B1-CDK1 inhibition. In vivo, in a rat infrarenal aortic anastomosis model (male Wistar rats, 10-12 weeks, 300-350 g), MMC-anchored sutures markedly reduced arterial wall thickening and α-SMA and PCNA accumulation at 4 and 12 weeks, without overt evidence of systemic toxicity. Notably, no measurable MMC release was detected under the tested conditions, supporting that the observed bioactivity is consistent with an interface-confined mechanism rather than bulk diffusion. This work establishes a non-releasing suture-based platform that delivers sustained molecular regulation of vascular healing through interface-confined control of VSMC behavior. Covalent drug anchoring transforms a clinically used suture into an active therapeutic interface, providing a promising strategy to prevent pathological vascular remodeling and anastomotic IH.
Huang et al. (Thu,) studied this question.