Advanced Silk Fibroin Biomaterials and Application to Small-Diameter Silk Vascular Grafts

Abstract

As the incidences of cardiovascular diseases have been on the rise in recent years, the need for small-diameter artificial vascular grafts is increasing globally. Although synthetic polymers such as expanded polytetrafluoroethylene or poly­(ethylene terephthalate) have been successfully used for artificial vascular grafts ≥6 mm in diameter, they fail at smaller diameters (<6 mm) due to thrombus formation and intimal hyperplasia. Thus, development of vascular grafts for small diameter vessel replacement that are <6 mm in diameter remains a major clinical challenge. Silk fibroin (SF) from Bombyx mori silkworm is well-known as an excellent textile and also has been used as suture material in surgery for more than 2000 years. Many attempts to develop small-diameter SF vascular grafts with <6 mm in diameter have been reported. Here, research and development in small-diameter vascular grafts with SF are reviewed as follows: (1) the heterogeneous structure of SF fiber (Silk II), including the packing arrangements and type II β-turn structure of SF (Silk I*) before spinning; (2) SF modified by transgenic silkworm, which is more suitable for vascular grafts; (3) preparation of small-diameter SF vascular grafts; (4) characterization of SF in the hydrated state, including dynamics of water molecules by nuclear magnetic resonance; and (5) evaluation of the SF grafts by in vivo implantation experiment. According to the findings, SF is a promising material for small-diameter vascular graft development.

Silk fibroin vascular graft: a promising tissue-engineered scaffold material for abdominal venous system replacement

“…Silk sericin is an antigenic gum-like protein that surrounds the SF core fibers 13 and can be removed through a degumming process 15 . SF biomaterial has biologic advantages, such as better biocompatibility, high affinity for cells, and susceptibility to proteolytic degradation in vivo without antigenicity 16,17 . Recently, experimental artery replacement using double-raschel knitted SF vascular grafts coated with an SF sponge was reported in animal models 18,19 .…”

3D Printing of Silk Protein Structures by Aqueous Solvent‐Directed Molecular Assembly

“…The backpressure of the microfluidic channel was up to 300 kPa, which covers the range of most applications of microfluidics as well as physiological blood pressures, promising for constructing artificial vascular grafts. Indeed, the silk is particularly suitable for constructing small‐diameter vascular grafts (<6 mm), because unlike synthetic polymers such as poly‐tetrafluoroethylene and poly(ethylene terephthalate) does not facilitate thrombus formation and intimal hyperplasia . Furthermore, 3D printing offers significant manufacturing flexibility in comparison with other techniques, including soft lithography, spinning, and coatings, for microfluidic chips and proteinaceous vascular grafts.…”

Development of Small-Diameter Elastin-Silk Fibroin Vascular Grafts

“…On the other hand, the circumferential compressive elastic modulus of the EL-SF graft (0.008 N/mm 2 ) was lower than the SF-coated SF graft (0.012 N/mm 2 ), as shown in Figure 4B. Thus, more favorable physical properties were obtained for the SF knitted graft by filling with EL sponge (Asakura et al, 2019). Figure 5 shows the (A) 13 C r-INEPT, (B) 13 C DD/MAS, and (C) 13 C CP/MAS NMR spectra of EL-SF grafts in the hydrated state, and (D) shows the 13 C CP/MAS spectrum of the graft in the dry state.…”

“…Therefore, it has also been used as a suture material for more than 2,000 years (Altman et al, 2003;Vepari and Kaplan, 2007;Thurber et al, 2015;Tamara et al, 2018;Holland et al, 2019). SF has been recently tried as a suitable candidate for vascular grafts <6 mm in diameter, as reviewed by Thurber et al (2015), Wang et al (2017), and by us (Asakura et al, 2019). SF vascular grafts are stiff and lacking in elasticity and need to be modified for better performance when transplanted in animals.…”