Fig 1.
A) Geometrical model of a 3D idealized portion of diseased superficial femoral artery (SFA), highlighting the computational grid employed within the wall at the inlet cross-section (on the left) and cross-section of the diseased portion characterized by the presence of a calcific plaque (on the right). B) Section along the longitudinal direction of the SFA model, with the definition of the computational domains and boundaries. ΩHEAL: healthy domain; ΩCALC: calcific plaque domain; ΩBLOOD: lumen domain (not meshed); ΓLUMEN: lumen wall; ΓBALL: lumen wall in contact with the balloon; ΓOP: lateral openings of the vessel wall; ΓADV: adventitial wall.
Fig 2.
Schematic representation of the biological process occurring during the cell cycle and the current understanding of the action of paclitaxel.
After the phase of growth and initial metabolic activity, the cell undergoes the phase of DNA replication and ulterior growth. Once maturity has been reached, the cell prepares for the mitotic process, which in physiological conditions would lead to cell division into two identical daughter cells. However, when the system is subjected to the anti-proliferative paclitaxel, the cell cycle is interrupted in the mitotic phase. The specific binding of paclitaxel molecules (CSB) to the intracellular microtubules determines their stabilization and impedes their reorganization essential for the cellular division. Part of the paclitaxel exchanged from the extracellular (CF) to the intracellular ambient (Ci) may remain unbound.
Table 1.
List of the parameters of the drug transport model.
Table 2.
List of the solver settings.
Fig 3.
Spatial maps of normalized specifically-bound (CSB) drug concentration on the section along the main direction in the case of DCB inflation of 180 seconds.
The temporal evolution is studied at 4 time instants: the beginning (t0) and end (tEND) of the DCB inflation, at 10 minutes (10 min) and 1 hour (1h) after DCB deflation. The location of the color maps is indicated at the top of the schematic.
Fig 4.
Impact of DCB inflation time on normalized free CF (A) and bound CSB (B) drug concentrations along the vessel wall thickness in healthy regions ΩHEAL. Results are displayed for inflation times of 60, 120 and 180 seconds. The location of the profile analyzed is indicated on the cross-section.
Fig 5.
Impact of the DCB inflation time on normalized free CF (A) and bound CSB (B) drug concentrations along the vessel wall thickness in the calcific regions ΩCALC. Results are displayed for inflation times of 60, 120 and 180 seconds. The location of the profile analyzed is indicated on the cross-section.
Fig 6.
Results of the sequential application of multiple DCBs.
Profiles along the wall thickness immediately after and 10 minutes after DCB application. Plots display (A) free (CF) and (B) specifically-bound (CSB) drug concentrations for the healthy region for the single (green line) and double (orange line) DCB applications. CF was normalized by the initial values (initial drug loading, 3.5 μg/mm2); CSB was normalized by the maximum measured values, namely at 1 hour from the DCB removal.
Fig 7.
Simulations of DCB inflation for (A) 60, (B) 120, and (C) 180 seconds in case of efficient blood wash-out (red) and coating retention (blue). The spatial profiles of the free CF and bound CSB drug concentrations are compared at 10 minutes (continuous line) and at 1 hour (dotted line) after DCB application. Both CF and bound CSB were normalized by their relative maximum values. CF was normalized by the initial values (initial drug loading); CSB was normalized by the maximum measured values, namely at 1 hour after the DCB removal. When not visible, the red dotted line is overlapped to red solid line.