Stratakos Efstathios, Tscheuschner Linnea, Vincenzi Lorenzo, Pedrinazzi Edoardo, Sigala Fragiska, D'Andrea Luca, Gastaldi Dario, Berti Francesca, Tzafriri Abraham Rami, Pennati Giancarlo
Laboratory of Biological Structure Mechanics, Department of Chemistry, Materials and Chemical Engineering "Giulio Natta", Politecnico di Milano, 20133, Milan, Italy.
Department of Vascular Surgery, National and Kapodistrian University of Athens, 15772, Athens, Greece.
Ann Biomed Eng. 2025 Mar;53(3):740-757. doi: 10.1007/s10439-024-03634-6. Epub 2024 Dec 12.
Drug-coated balloons (DCBs) aim to deliver drug-loaded surface coating upon inflation at specific vascular sites, yet the role of inflation pressure remains to be defined. We implement a new approach combining ex vivo stamping experiments with in silico simulations to study acute coating transfer by commercial DCBs. This methodology comprises 3 essential pillars: (I) DCB resin inflation and slicing into cylindrical segments for subsequent stamping onto porcine-excised tissue, (II) Numerical inflation of a full DCB replica in an idealized porcine vessel to predict in vivo interfacial contact pressures (CPs) and subsequent interfacial-level numerical stamping to calculate appropriate benchtop forces that recreate these in vivo CP values, and (III) ex vivo stamping experiments and optical analysis of the stamped surfaces (DCB segment and arterial tissue), using a standard high-resolution camera to visualize coating. High-performance liquid chromatography (HPLC) was employed as a validated assay for quantifying drug in tissue samples post-stamping. HPLC analysis revealed a significant correlation with image processing, confirming the validity of the optical method as a tool to quantify DCB coating. Image and HPLC analysis revealed a statistically significant twofold rise in coating area and drug content to tissue, respectively, when the average CP roughly doubled (0.16-0.35 atm) and a non-statistically significant increase in coating area and drug content with a further rough doubling of average CP (0.35 to 0.75 atm). Imaging of DCB segments pre- and post-stamping showed transfer of partial coating thickness at low CP, contrasting with complete transfer at high CP at the same site. 3D confocal images of DCB surfaces revealed variable thickness in the transferred coating. This study introduces a comprehensive methodology for evaluating the efficacy of commercial DCB coating transfer to arterial tissue-a crucial precursor to drug elution studies-while minimizing the number of DCBs needed and improving variable control and realism.
药物涂层球囊（DCB）旨在通过在特定血管部位充气时输送载药表面涂层，但充气压力的作用仍有待确定。我们采用一种新方法，将体外冲压实验与计算机模拟相结合，以研究商用DCB的急性涂层转移。该方法包括3个基本支柱：（I）将DCB树脂充气并切成圆柱形段，以便随后冲压到猪切除的组织上；（II）在理想化的猪血管中对完整的DCB复制品进行数值充气，以预测体内界面接触压力（CP），随后进行界面级数值冲压，以计算重现这些体内CP值所需的合适台面力；（III）体外冲压实验和对冲压表面（DCB段和动脉组织）的光学分析，使用标准高分辨率相机可视化涂层。采用高效液相色谱（HPLC）作为验证后的分析方法，对冲压后组织样品中的药物进行定量。HPLC分析显示与图像处理有显著相关性，证实了光学方法作为量化DCB涂层工具的有效性。图像和HPLC分析显示，当平均CP大致翻倍（0.16 - 0.35个大气压）时，涂层面积和组织中的药物含量分别有统计学意义的两倍增长，而当平均CP进一步大致翻倍（0.35至0.75个大气压）时，涂层面积和药物含量有非统计学意义的增加。冲压前后DCB段的成像显示，在低CP时部分涂层厚度发生转移，而在同一位点高CP时则完全转移。DCB表面的三维共聚焦图像显示转移涂层的厚度各不相同。本研究引入了一种综合方法，用于评估商用DCB涂层向动脉组织转移的效果——药物洗脱研究的关键前提——同时尽量减少所需DCB的数量，并改善变量控制和真实性。
