Abstract
Current synthetic vascular grafts are not suitable for use in low-diameter applications. Silk fibroin is a promising natural graft material which may be an effective alternative. In this study, we compared two electrospun silk grafts with different manufacturing processes, using either water or hexafluoroisopropanol (HFIP) as solvent. This resulted in markedly different Young’s modulus, ultimate tensile strength and burst pressure, with HFIP spun grafts observed to have thicker fibres, and greater stiffness and strength relative to water spun. Assessment in a rat abdominal aorta grafting model showed significantly faster endothelialisation of the HFIP spun graft relative to water spun. Neointimal hyperplasia in the HFIP graft also stabilised significantly earlier, correlated with an earlier SMC phenotype switch from synthetic to contractile, increasing extracellular matrix protein density. An initial examination of the macrophage response showed that HFIP spun conduits promoted an anti-inflammatory M2 phenotype at early timepoints while reducing the pro-inflammatory M1 phenotype relative to water spun grafts. These observations demonstrate the important role of the manufacturing process and physical graft properties in determining the physiological response. Our study is the first to comprehensively study these differences for silk in a long-term rodent model.
Highlights
Current synthetic vascular grafts are not suitable for use in low-diameter applications
We demonstrate that changing the silk manufacturing process and altering the fibre thickness and porosity of electrospun silk vascular grafts has a profound effect on vascular remodelling in a rat abdominal aorta grafting model
We systematically explored spinning conditions for scaffolds spun from water (Supplementary Fig. 1) and from HFIP (Supplementary Fig. 2)
Summary
Current synthetic vascular grafts are not suitable for use in low-diameter applications. An initial examination of the macrophage response showed that HFIP spun conduits promoted an antiinflammatory M2 phenotype at early timepoints while reducing the pro-inflammatory M1 phenotype relative to water spun grafts These observations demonstrate the important role of the manufacturing process and physical graft properties in determining the physiological response. This work demonstrates that modulating electrospinning parameters to increase fibre and pore size of silk vascular grafts enhances their in vivo remodelling by the host, resulting in improved functional outcomes. These findings prompt consideration of other parameters within the manufacturing processes of silk which may further enhance their performance as synthetic vascular grafts
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