Construction of tissue-engineered vascular grafts with enhanced patency by integrating heparin, cell-adhesive peptide, and carbon monoxide nanogenerators into acellular blood vessels.
Construction of tissue-engineered vascular grafts with enhanced patency by integrating heparin, cell-adhesive peptide, and carbon monoxide nanogenerators into acellular blood vessels.
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DOI：
10.1016/j.bioactmat.2023.12.015
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发表时间：
2024-04
影响因子：
18.9
通讯作者：
中科院分区：
文献类型：
--
作者：
小直径组织工程血管移植物(SdTEVGs)作为一种潜在的血管旁路移植和替代治疗方法，已经引起了人们的广泛关注。然而，在移植过程中，内膜增生和血栓形成是影响移植物通畅性的两个主要并发症。为了解决这一问题，我们构建了基于共价有机骨架(COF)的一氧化碳(CO)纳米生成器，并与LXW-7肽和肝素共固定，在由无细胞血管构建的TEVGs上建立了多功能表面，以防止血栓形成和狭窄。细胞粘附肽LXW-7可捕获内皮形成细胞(EFCS)促进内皮化，而抗血栓分子肝素则可防止血栓形成。活性氧(ROS)引发的CO释放抑制巨噬细胞的黏附和活化，导致ROS和炎症因子的减少。因此，炎症引发的内皮-间充质转化(EndMT)受到抑制，有助于维持新生内皮的动态平衡，防止TEVGs的病理性重构。当移植到体内时，这些血管移植物表现出微乎其微的内膜增生，并且保持通畅3个月。这一成果为构建抗血栓和抗增生性TEVGs提供了新的途径。通过将肝素、细胞粘附肽和一氧化碳纳米生成器整合到无细胞血管中，构建了组织工程化血管移植物。细胞粘附肽可以捕获内皮形成细胞，促进内皮化，而肝素固定化有助于抑制血栓形成。活性氧引发的一氧化碳释放可通过促进炎症消退来消除内皮细胞向间充质细胞转化所致的TEVGs的病理重构。这些多功能的组织工程化血管移植物在植入过程中显示出更好的通畅性，没有血栓形成和严重的内膜增生。
Small-diameter tissue-engineered vascular grafts (sdTEVGs) have garnered significant attention as a potential treatment modality for vascular bypass grafting and replacement therapy. However, the intimal hyperplasia and thrombosis are two major complications that impair graft patency during transplantation. To address this issue, we fabricated the covalent-organic framework (COF)-based carbon monoxide (CO) nanogenerator-and co-immobilized with LXW-7 peptide and heparin to establish a multifunctional surface on TEVGs constructed from acellular blood vessels for preventing thrombosis and stenosis. The cell-adhesive peptide LXW-7 could capture endothelial-forming cells (EFCs) to promote endothelialization, while the antithrombotic molecule heparin prevented thrombus formation. The reactive oxygen species (ROS)-triggered CO release suppressed the adhesion and activation of macrophages, leading to the reduction of ROS and inflammatory factors. As a result, the endothelial-to-mesenchymal transition (EndMT) triggered by inflammation was restricted, facilitating the maintenance of the homeostasis of the neo-endothelium and preventing pathological remodeling in TEVGs. When transplanted in vivo, these vascular grafts exhibited negligible intimal hyperplasia and remained patent for 3 months. This achievement provided a novel approach for constructing antithrombotic and anti-hyperplastic TEVGs. Tissue-engineered vascular grafts have been constructed by integrating heparin, cell-adhesive peptide, and carbon monoxide nanogenerators into acellular blood vessels. The cell-adhesive peptide can capture endothelial-forming cells to promote endothelialization, while the heparin immobilization facilitates the inhibition of thrombus formation. Reactive oxygen species-triggered carbon monoxide release can eliminate endothelial-to-mesenchymal transition-induced pathological remodeling in the TEVGs by promoting inflammatory resolution. These multifunctional tissue-engineered vascular grafts have shown enhanced patency without thrombosis and severe intimal hyperplasia during implantation.
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