The development of small-diameter vascular grafts that can meet the long-term patency required for implementation in clinical practice presents a key challenge to the research field. Although techniques such as the braiding of scaffolds can offer a tunable platform for fabricating vascular grafts, the effects of braided silk fiber skeletons on the porosity, remodeling, and patency in vivo have not been thoroughly investigated. Here, we used finite element analysis of simulated deformation and compliance to design vascular grafts comprised of braided silk fiber skeletons with three different degrees of porosity. Following the synthesis of low-, medium-, and high-porosity silk fiber skeletons, we coated them with hemocompatible sulfated silk fibroin sponges and then evaluated the mechanical and biological functions of the resultant silk tubes with different porosities. Our data showed that high-porosity grafts exhibited higher elastic moduli and compliance but lower suture retention strength, which contrasted with low-porosity grafts. Medium-porosity grafts offered a favorable balance of mechanical properties. Short-term in vivo implantation in rats indicated that porosity served as an effective means to regulate blood leakage, cell infiltration, and neointima formation. High-porosity grafts were susceptible to blood leakage, while low-porosity grafts hindered graft cellularization and tended to induce intimal hyperplasia. Medium-porosity grafts closely mimicked the biomechanical behaviors of native blood vessels and facilitated vascular smooth muscle layer regeneration and polarization of infiltrated macrophages to the M2 phenotype. Due to their superior performance and lack of occlusion, the medium-porosity vascular grafts were evaluated in long-term (24-months) in vivo implantation. The medium-porosity grafts regenerated the vascular smooth muscle cell layers and collagen extracellular matrix, which were circumferentially aligned and resembled the native artery. Furthermore, the formed neoarteries pulsed synchronously with the adjacent native artery and demonstrated contractile function. Overall, our study underscores the importance of braided silk fiber skeleton porosity on long-term vascular graft performance and will help to guide the design of next-generation vascular grafts.
Sepsis is a common cause of acute lung injury (ALI), often accompanied by immune disorders and a high mortality rate. Cuproptosis is a recently discovered form of cell death that participates in the progression of various diseases. There is no information on the role of cuproptosis in sepsis-associated ALI. Data from the Gene Expression Omnibus (GEO) database were used for a comprehensive analysis of the transcriptional changes and role of cuproptosis-related genes (CRGs) in sepsis-associated ALI. Gene enrichment analysis, the WGCNA and CIBERSORT algorithms, and consensus clustering were used to explore the relationships between CRGs and immune cells, as well as the underlying mechanisms. We found that fourteen CRGs that showed significant differences in expression between sepsis-associated ALI and healthy controls. Two different CRG subtypes were identified. The scores of the CRG and gene clusters were consistent, and the expression of immune-related factors in the two clusters was similar. Infiltration of immune cells differed between the subgroups, indicating an association between the subgroups and immune cell. A CRG-scoring model was constructed, and was effective in predicting the incidence of sepsis-associated ALI through the expression of CRGs. Real-time PCR analysis showed that the expression of CRGs in the sepsis-associated ALI cell model was similar to that seen in CRG cluster B. CRGs were found to be significantly associated with the occurrence, immune characteristics, and biological processes of sepsis-associated ALI. These findings provide new insights into the mechanisms underlying sepsis-associated ALI.
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