Hybrid in silico and ex vivo models for quantitative evaluation of acute coating transfer in Drug-Coated Balloon angioplasty

Drug-coated balloons (DCBs) have emerged as promising devices for treating cardiovascular diseases, offering localized drug delivery during angioplasty while supporting the "leave nothing behind" strategy. However, their clinical potential is hindered by limited drug-coating transfer to target tissues and a poor understanding of the factors influencing drug distribution. Key parameters such as inflation pressure, device design and vessel characteristics remain inadequately explored. This PhD dissertation investigates the complex interactions between DCBs and vascular tissues during tracking and inflation at target sites. Through experimental studies, computational modeling, and preclinical evaluations, the research highlights mechanisms contributing to off-target or on-target drug delivery during DCB angioplasty. Key achievements include the development of the first finite element model of angioplasty balloon unfolding to study balloon-tissue interactions and an ex vivo model to evaluate acute coating transfer under controlled conditions mimicking in vivo scenarios. Furthermore, a digital twin of a commercial DCB was created to simulate deployment in vivo, correlating contact pressure maps with observed coating distribution patterns in animal studies. This work identifies critical factors influencing drug transfer, such as vessel local oversizing, angioplasty balloon design, and shear stresses during navigation through arterial bends, which can lead to off-target drug loss. By proposing a rigorous framework for evaluating acute coating transfer, this research provides valuable tools for both academic studies and the medical device industry to optimize DCB performance and advance the development of next-generation devices.