Challenges and strategies for in situ endothelialization and long-term lumen patency of vascular grafts

Vascular diseases are the most prevalent cause of ischemic necrosis of tissue and organ, which even result in dysfunction and death. Vascular regeneration or artificial vascular graft, as the conventional treatment modality, has received keen attentions. However, small-diameter (diameter < 4 mm) vascular grafts have a high risk of thrombosis and intimal hyperplasia (IH), which makes long-term lumen patency challengeable. Endothelial cells (ECs) form the inner endothelium layer, and are crucial for anti-coagulation and thrombogenesis. Thus, promoting in situ endothelialization in vascular graft remodeling takes top priority, which requires recruitment of endothelia progenitor cells (EPCs), migration, adhesion, proliferation and activation of EPCs and ECs. Chemotaxis aimed at ligands on EPC surface can be utilized for EPC homing, while nanofibrous structure, biocompatible surface and cell-capturing molecules on graft surface can be applied for cell adhesion. Moreover, cell orientation can be regulated by topography of scaffold, and cell bioactivity can be modulated by growth factors and therapeutic genes. Additionally, surface modification can also reduce thrombogenesis, and some drug release can inhibit IH. Considering the influence of macrophages on ECs and smooth muscle cells (SMCs), scaffolds loaded with drugs that can promote M2 polarization are alternative strategies. In conclusion, the advanced strategies for enhanced long-term lumen patency of vascular grafts are summarized in this review. Strategies for recruitment of EPCs, adhesion, proliferation and activation of EPCs and ECs, anti-thrombogenesis, anti-IH, and immunomodulation are discussed. Ideal vascular grafts with appropriate surface modification, loading and fabrication strategies are required in further studies.