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Article by Yi Wu & Margaretha Morsink
Engineering Surface Coating of Implantable Vascular Devices
Implantable vascular devices provide life-saving solutions for patients with cardiovascular diseases, ensuring proper blood flow in cases where natural vessels are damaged or blocked. However, while widely performed in clinical treatment, patients sustain high failure rates and poor long-term stability due to thrombosis and intimal hyperplasia. Thrombosis is the formation of a blood clot, or thrombus, within a blood vessel, which can obstruct blood flow, whereas intimal hyperplasia is an abnormal thickening of the innermost layer of the blood vessel. To address this issue, this paper designs a novel surface coating for prosthetic vascular devices to mimic the natural human vascular environment. The coating prevents platelet adhesion and selectively captures endothelial progenitor cells (EPC), facilitating better integration of the device with the body.
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What did these researchers do?
Researchers developed a bioactive, three-layer coating inspired by the failure mechanisms of vascular devices and the physiological functions of native endothelium. The base layer is made of expanded polytetrafluoroethylene (ePTFE), a non-reactive, hydrophobic polymer known for its high biocompatibility, chemical resistance, and mechanical strength. The first coating layer on ePTFE is parylene, which provides excellent mechanical flexibility and long-lasting adherence to the device surface, forming P-ePTFE. Next, polyethylene glycol (PEG) is attached to create PP-ePTFE. PEG is used for its ability to prevent platelet adhesion and to serve as a multifunctional linker for attaching functional molecules to the surface. Finally, LXW7, an EPC specific binding ligand, is covalently attached to form the PPL-ePTFE surface. This novel three-layer coating is designed to preferentially recruit EPCs over platelets and other cells, promoting rapid reendothelialization at the early stage. The newly formed endothelium then further inhibits platelet adhesion and aggregation, thereby preventing the formation of blood clots and enhancing the long-term performance of the vascular device.
Why is this important?
This bioactive parylene-based conformal coating addresses the issue of the absence of functional, “living” endothelium on prosthetic surfaces. This is important, because medical devices often have issues reintegrating with the human body. Endothelization enables the reintegration with the human body, which ultimately results in less complications, such as thrombosis. The versatility of the coating and ease of application to existing devices without altering surgical practices makes it a practical solution for improving patient outcomes. By enhancing long-term device performance, the coating reduces complications such as thrombosis, potentially lowering healthcare costs associated with device failures.
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How did the researchers do this?
Researchers used two different pig models (carotid artery interposition model and carotid artery-jugular vein arteriovenous graft model) to validate the efficacy of the 3-layer coating in vivo. Macroscopical imaging revealed that PPL-ePTFE grafts showed almost no thrombosis, in contrast to the visible thrombosis observed on the luminal surface of ePTFE grafts. Further analysis using H&E staining confirmed the presence of thrombosis and intimal hyperplasia in the ePTFE grafts, while these complications were notably reduced in the PPL-ePTFE grafts. The graft patency area was significantly higher in PPL-ePTFE grafts, suggesting better long-term stability and function. Scanning electron microscopy provided detailed evidence, showing that while ePTFE grafts had significant platelet adhesion, aggregation, and red cell clumps, the PPL-ePTFE grafts had minimal platelet presence, indicating a strong ability to inhibit these undesirable effects. Furthermore, immunofluorescence staining with anti-CD31 antibodies revealed extensive CD31+ endothelial cell (EC) coverage on the luminal surface of PPL-ePTFE grafts, whereas only sparse CD31+ECs were found on ePTFE grafts. This result suggests that the PPL-ePTFE grafts promote endothelialization more effectively, contributing to better integration with the vascular environment and reducing the risk of complications like thrombosis and intimal hyperplasia.
Schematic of the functions of PPL-ePTFE grafts on platelet adhesion, EPC adhesion, and proliferation.
What comes next?
The study has demonstrated the preliminary success of PPL-ePTFE grafts in vivo in terms of its potential to enhance endothelialization and reduce thrombosis on vascular devices. However, challenges remain before this technology can be translated into widespread clinical use. More extensive animal studies using clinical-grade materials need to be done to ensure the coating’s safety, effectiveness, and scalability. These studies should include long-term evaluations in the scale of years to assess the durability of the endothelialization, the coating’s ability to prevent thrombosis and intimal hyperplasia over extended periods, as well as biocompatibility tests and manufacturing scale-up. Beyond vascular grafts, this coating could revolutionize treatments for chronic vascular diseases such as coronary artery disease and peripheral artery disease, potentially preventing severe outcomes like heart transplants and limb loss. Additionally, its application can extend to other medical devices, including stents, cardiac valves, and catheters. The coating also serves as a platform for delivering biologics, further enhancing the regenerative potential of these devices, making it a significant development in both vascular medicine and regenerative therapies.
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