A protective device for the pathological process of graft vein restenosis after CABG
B Wang, Y Yu, H Li, Y LiuAbstract
Introduction
Coronary artery bypass grafting (CABG) is a guideline-recommended treatment for severe coronary heart disease. The great saphenous vein is used as a bypass graft in approximately 80% of cases [2], and its patency critically determines patient prognosis. The primary mechanisms of graft failure are time-dependent: thrombosis predominates within the first week after CABG, followed by intimal hyperplasia from one month to one year, and subsequent atherosclerotic changes in the transplanted vessels after one year [3].
Purpose
To address the pathological process of restenosis, we developed a hydrogel microneedle-based vein graft protection device capable of stage-specific drug release. Tirofiban is incorporated to prevent thrombosis, rapamycin to inhibit intimal hyperplasia, and rosuvastatin to suppress the progression of atherosclerosis.
Methods
Transmission electron microscopy (TEM) was used to observe the physical morphology of the device. Infrared spectroscopy was employed to evaluate drug incorporation into the device, and liquid chromatography-mass spectrometry (LC-MS) was used to assess in vitro drug release profiles. A mouse jugular vein transplantation model was established, including a control group, a drug-only control group, a blank device group, and a drug-loaded device group. Immunofluorescence staining was performed to observe drug distribution within the vascular endothelium at different stages. Ultrasound imaging was used to monitor the patency of transplanted veins. The CCK-8 assay was conducted to evaluate the safety of the drugs, and a hemolysis test was performed to assess the biocompatibility of the device.
Results
In vitro characterization of the device is shown in Figure 1.Panel A illustrates the preparation process.Panels B, C, and D show the naked-eye view, 60× magnified image, and TEM micrograph of the device, respectively. Panel E presents the infrared spectrum, confirming successful incorporation of all drugs.Panel F shows the in vitro drug release curve, indicating a staged release profile. Panel G depicts the mechanical properties of the device, demonstrating sufficient strength to penetrate the vascular adventitia. Panels H1, H2, and H3 display immunofluorescence images at 1 week, 1 month, and 1 year after surgery, respectively. At one week post-surgery, tirofiban was the predominant drug detected in the vascular endothelium; at one month, rapamycin was dominant; and at one year, rosuvastatin was primarily observed. Figure 2 summarizes the in vivo results. Panel A presents the lumen patency rates of each group at different time points,the device group improved the patency rate of the lumen at all stages. Panels B and C show the CCK-8 and hemolysis test results, respectively. Together, these findings demonstrate the effectiveness and safety of the device.
Conclusions
We have developed a safe and effective protective device targeting the pathological process of vein graft restenosis after CABG.Figure 1For image description, please refer to the figure legend and surrounding text.Figure 2For image description, please refer to the figure legend and surrounding text.