The Regulatory Effect of Braided Silk Fiber Skeletons with Differential Porosities on In Vivo Vascular Tissue Regeneration and Long-Term Patency

Abstract

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.