How does stent expansion alter drug transport properties of the arterial wall?

Abstract

Stents have become the most successful device to treat advanced atherosclerotic lesions. However, one of the main issues with these interventions is the development of restenosis. The coating of stents with antiproliferative substances to reduce this effect is now standard, although such drugs can also delay re-endothelialization of the intima. The drug release strategy is therefore a key determinant of drug-eluting stent efficacy. Many mathematical models describing drug transport in arteries have been developed and, usually separately, models describing the mechanics of arterial tissue have been devised. However, the literature is lacking a comprehensive model that adequately takes into account both the mechanical deformation of the porous arterial wall and the resulting impact on drug transport properties. In this paper, we provide the most comprehensive study to date of the effect of stent mechanical expansion on the drug transport properties of a three-layer arterial wall. Our model incorporates the state-of-the art description of the mechanical properties of arterial tissue though an anisotropic, hyperelastic material model and includes a nonlinear saturable binding model to describe drug transport in the arterial wall. We establish relationships between mechanical force generated through device expansion and alteration in diffusion within the arterial wall and perform simulations to elucidate the impact of such alterations in spatio-temporal drug release and tissue uptake. Mechanical deformation of the arterial wall results in modified drug transport properties and tissue drug concentrations, highlighting the importance of coupling solid mechanics with drug transport.

Keywords: Anisotropic hyperelastic material; Arterial wall; Coupling mechanics-drug transport; Drug transport; Drug-eluting stent; Mechanical expansion.