Altered processing enhances the efficacy of small-diameter silk fibroin vascular grafts

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.

Dual-Crystallizable Silk Fibroin/Poly(L-lactic Acid) Biocomposite Films: Effect of Polymer Phases on Protein Structures in Protein-Polymer Blends

“…SEM images illustrated the silk fibroin blends with poly(L-lactic acid) homogeneously at the macroscopic level. In addition, the interlacing, bridged morphology between the two polymer chains can prevent crack propagation and improve the thermal stability and degradability of the materials [ 1 , 2 , 3 , 12 , 19 ].…”

“…For the raw PLLA sample ( Figure 2 a, SP-0/5), the absorption peak at 1752 cm −1 is the characteristic absorption band of C=O on the molecular chain [ 12 , 13 ]. The peaks at 1447 cm −1 and 1358 cm −1 are from the deformation and absorption vibration of C-H, respectively [ 1 , 2 , 14 , 17 ]. Both the 1186 cm −1 and the 1092 cm −1 peaks belong to C-O stretching vibrations [ 1 , 2 , 14 , 17 ].…”

“…The peaks at 1447 cm −1 and 1358 cm −1 are from the deformation and absorption vibration of C-H, respectively [ 1 , 2 , 14 , 17 ]. Both the 1186 cm −1 and the 1092 cm −1 peaks belong to C-O stretching vibrations [ 1 , 2 , 14 , 17 ]. For the pure SF sample ( Figure 2 a, SP-5/0), the main infrared spectral regions within 1700~1600 cm −1 and 1600~1500 cm −1 are assigned to the peptide backbone of the amide I and amide II absorptions, respectively [ 1 , 2 , 8 , 12 , 20 ].…”

“…In recent years, silk fibroin (SF) extracted from the natural silkworm cocoon has attracted attention as one of the most promising bioengineering materials due to its unique molecular structure, excellent biocompatibility, morphologic flexibility, ability to promote cell adhesion and growth, and lower inflammatory response [ 1 , 2 , 3 , 4 , 5 , 6 ]. SF is easily transformed into various tunable morphologies such as nanofibers, thin films, and particles by controlling the secondary structure of SF proteins.…”

“…However, it is difficult for a single material to fit all the requirements of a specific biological function or a desired application because of defects in individual material properties. For SF, these defects include low mechanical strength, poor stability, poor thrombogenicity, and easy hydrolysis of regenerated SF [ 1 , 7 ]. Therefore, an active strategy is blending different materials to enhance the overall properties to create a polymeric composite material through a synergistic combination of the desirable properties from original components [ 1 , 2 , 7 ].…”