Biomimetic design strategies for synthetic small-diameter vascular grafts

Cardiovascular diseases (CVDs) remain the leading cause of mortality worldwide. The limitations of autologous grafts, along with the long-term failure of allogeneic alternatives, underscore the urgent need for the development of synthetic vascular grafts in advanced-stage treatment. Large-diameter synthetic grafts (greater than 6 mm) have demonstrated clinical success, and synthetic small-diameter vascular grafts (SSDVGs) continue to demonstrate significant drawbacks, such as compliance mismatch, poor endothelialization, intimal hyperplasia, and thrombosis, all of which reduce long-term patency. Despite considerable progress in materials and fabrication techniques, the structural biomimetic design of SSDVGs, which is critical for mechanical performance and biological integration, has not been improved and thus continues to hinder clinical translation. This review addresses this gap by exploring design strategies inspired by native vascular architecture. It examines recent advances in synthetic material suitable for SSDVGs; structural configurations, such as fiber-based, segmented, embedded, and layered designs that improve compliance; surface topography modifications that guide endothelial cell migration and proliferation to promote in situ endothelialization; and surface functionalization involving anticoagulants, growth factors, and cellular or genetic agents to enhance hemocompatibility and prevent thrombosis. Furthermore, this paper identifies current challenges and future research directions. Overall, integrated biomimetic strategies offer a promising pathway to improve SSDVG performance and expand clinical options for the treatment of CVDs.