ABSTRACT
Introduction
Intimal hyperplasia (IH) is a significant factor limiting the success of revascularization surgery for blood flow restoration. IH results from a foreign body response and mechanical disparity that involves complex biochemical reactions resulting in graft failure. The available treatment option utilizes either different pharmacological interventions or mechanical support to the vascular grafts with limited success.
Areas covered
This review explains the pathophysiology of IH, responsible mechanical and biological factors, and treatment options, emphasizing perivascular devices. They are designed to provide mechanical support and pharmacology actions. The perivascular drug delivery concept has successfully demonstrated efficacy in various animal studies. Accurate projections of drug release mechanisms using mathematical modeling could be used to formulate prolonged drug elution devices. Numerical modeling aspects for the prediction of design outcomes have been given due importance that fulfills the unmet clinical need for better patient care.
Expert opinion
IH could be effectively prevented by simultaneous mechanical scaffolding and sustained local drug delivery. Future perivascular medical devices could be designed to integrate these essential features. Numerical modeling for device performance prediction should be utilized in the development of next-generation perivascular devices.
Article highlights
Intimal hyperplasia (IH) significantly reduced the success of revascularization surgical procedures such as coronary artery bypass grafting (CABG), saphenous vein grafts (SVGs), and arteriovenous (AV) fistula for hemodialysis.
IH is an intense foreign body response involving complex biochemical reactions resulting in blood vessel narrowing.
Available treatment focuses on the systemic administration of pharmacology agents and external mechanical support. The most promising treatment would be the drug–device combination using perivascular drug-eluting medical devices such as wraps, sheaths, and coils.
The drug release kinetics could be optimized using computational mathematical modeling. These methods would accelerate the device development program by precisely finding the factors governing the drug elution kinetics. The mathematical models could be further explored to design future drug-eluting implantable perivascular devices.
Abbreviations and nomenclature
AV | = | Arteriovenous |
CABG | = | Coronary artery bypass grafting |
a | = | radius of a cylinder or sphere or the half-thickness of a slab |
a0 | = | initial radius |
b0 | = | initial thickness |
c0 | = | initial drug concentration within the matrix |
D | = | Diffusion coefficient of drug within the polymeric matrix |
Ds | = | Diffusion coefficient of the solvent |
EC | = | Endothelial cell |
ECM | = | Extracellular matrix |
EEL | = | External elastic lamina |
fPCL | = | fraction of PCL |
fPLGA | = | fraction of PLGA |
h | = | Thickness of the device |
HMG-CoA | = | Hydroxy methyl glutaryl co-enzyme A |
IEL | = | Internal elastic lamina |
IH | = | Intimal hyperplasia |
k | = | Release constant of Higuchi (Higuchi model) |
ka | = | radial erosion rate constant |
kb | = | axial erosion rate constant |
kd | = | Disentanglement rate of polymer chains |
kd | = | Kinetic dissolution constant (Zero order) |
krt | = | constant for geometrical characteristics and structural modifications of the system (Ritger-Peppas model) |
K1 | = | First order rate constant (First order) |
k1 and k2 | = | Constants (Peppas and Sahlin, Alfrey model) |
l | = | Half thickness of the polymer |
M0 | = | Total mass of drug incorporated within the device |
Md and Mt | = | Amount of drug released at time t |
Md,∞ and M∞ | = | Amount of drug released at infinite time |
m | = | Fickian diffusion exponent of the system (Peppas-Sahlin model) |
n | = | shape factor (n = 3 for spherical; n = 2 for cylindrical and n = 1 for slab) |
n | = | exponent of drug release (Ritger-Peppas model) |
ɸb,PCL | = | fraction of burst release from PCL phase |
PCI | = | Percutaneous coronary interventions |
PCL | = | Poly ε-caprolactone |
PEG | = | Polyethylene glycol |
PLA | = | Poly lactic acid |
PLGA | = | Poly lactic-co-glycolic acid |
PPG | = | Polypropylene glycol |
PTFE | = | Polytetrafluoroethylene |
SFA | = | Superficial femoral artery |
SMC | = | Smooth muscle cell |
υ1,eq and υd,eq | = | Equilibrium concentrations of solvent and drug respectively |
υ1* and υd* | = | Characteristic concentrations of solvent and drug respectively |
VSMC | = | Vascular smooth muscle cell |
Declaration of interest
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
Reviewers disclosure
Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.
Supplementary material
Supplemental data for this article can be accessed online at https://doi.org/10.1080/17434440.2023.2244875