Manusree Bhatter

Background: Cardiovascular diseases (CVDs) are a leading cause of death globally, accounting for almost 19 million deaths globally¹. Coronary Artery Disease (CAD) is a lethal CVD, and it accounts for approximately 610,000 death every year in the United States and is a major source of healthcare costs². CAD is caused by atherosclerotic plaque formation in the coronary arteries of the heart, which leads to varying levels of artery lumen obstruction³. Rupture of these plaques followed by thrombotic coronary artery vessel occlusion can lead to myocardial infarction, which is the major mechanism of death from CAD³. Elective revascularization of the small-caliber coronary arteries through CABG (Coronary Artery Bypass Graft) is needed for patients who do not respond to medical therapy and is one of the most widely used treatments for CAD². However, issue occurs with the fact that autologous vessel grafts for repair of small-caliber vessels, such as in CABG, have unavailability of adequate vessels for graft harvesting and poor quality of vessels, especially in those with severe atherosclerosis⁵. Synthetic graft materials are useful for medium and large diameter arterial grafts but are ineffective for smaller diameter grafts (<5 mm) due to thrombogenicity, low patency rates, and compliance mismatch⁵. Due to these complications, there is a demand for easy-to-handle small-diameter artificial vascular grafts, and the latest advances show great promise with electrospun silk-fibroin grafts and elastin-silk fibroin grafts⁶.

Objective: In this narrative review, we explored the main silk-fibroin vascular graft solutions being investigated and benefits and drawbacks of each solution.

Search Methods: An online search on the PubMed database was conducted from 2018 to 2023 with the following keywords: “tissue engineered vascular grafts”, “electrospun silk fibroin grafts”, “coronary artery disease”, “cardiovascular disease”.

Results: Monolayer electrospun silk fibroin tubes for small vessel bypass graft were investigated and showed great promise⁷. Within the physiological blood pressure range of 80-120 mmHg, the silk fibroin tube’s compliance was better than autologous vessel grafts⁷. In vitro cytocompatibility tests on silk-fibroin tubes using NIH 3T3 fibroblasts showed good cell viability and motility⁷. Assessment of mechanical properties showed higher strain at break and excellent suture retention strength, burst pressure, and distensibility⁸. In vivo functionality tests on the abdominal aorta of rats confirmed excellent mechanical properties⁸. Another approach to silk-fibroin graft, SilkGraft, is a three-layered small-caliber vascular graft made with silk fibroin and an intermediate textile layer⁹. In vitro studies showed an excellent level of biocompatibility and cell adhesion. There was a lack of complement activation, indicating good blood hemocompatibility⁹. In vivo tests on sheep showed that SilkGraft was easy to handle and surgically stitch. Improvements were made to SilkGraft to improve kink resistance and mechanical strength¹⁰. Improved mechanical properties were seen with tensile strength, compliance, and kink resistance¹⁰. Elastin-silk fibroin grafts were investigated. Cell and platelet adhesion experiments showed that elastin had a higher attachment rate of endothelial cells and lower platelet adhesion rates, indicating possible anti-thrombotic properties⁶. Elastin-silk fibroin grafts had higher tensile strength and lower circumferential elastic modulus, showing that elastin-silk fibroin grafts have better physical properties⁶. In vivo experiments with elastin-silk fibroin grafts in rats demonstrated that no granuloma was formed, indicating excellent usability in vivo⁶.

Conclusions: Electrospun silk fibroin and elastin-silk fibroin grafts showed great promise for use in small vessel arterial grafts through in vitro and in vivo biocompatibility testing. These can potentially be used in the future for CABGs and other small-artery vascular grafts.

Works Cited:

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