A Novel Hybrid Silk Fibroin/Polyurethane Arteriovenous Graft for Hemodialysis: Proof‐of‐Concept Animal Study in an Ovine Model

Abstract

To solve the problem of vascular access failure, a novel semi-degradable hybrid vascular graft, manufactured by electrospinning using silk fibroin and polyurethane (Silkothane), has been previously developed and characterized in vitro. This proof-of-concept animal study aims at evaluating the performances of Silkothane grafts in a sheep model of arteriovenous shunt, in terms of patency and short-term remodeling. Nine Silkothane grafts are implanted between the common carotid artery and the external jugular vein of nine sheep, examined by palpation three times per week, by echo-color Doppler every two weeks, and euthanized at 30, 60, and 90 days (N = 3 per group). At sacrifice, grafts are harvested and submitted for histopathology and/or scanning electron microcopy (SEM). No cases of graft-related complications are recorded. Eight of nine sheep (89%) show 100% primary unassisted patency at the respective time of sacrifice (flow rate 1.76 ± 0.61 L min −1 , one case of surgery-related thrombosis excluded). Histopathology and SEM analysis evidence signs of inflammation and pseudointima inside the graft lumen, especially at the venous anastomosis; however, endoluminal stenosis never impairs the functionality of the shunt and coverage by endothelial cells is observed. In this model, Silkothane grafts grant safety and 100% patency up to 90 days.

Structural investigations of polyurethane and silk‐polyurethane composite fiber studied by 13C solid‐state NMR spectroscopy

“…So far, there are many papers about SF-PU composite materials to use them as biomaterials. 13,25,[28][29][30][31][32][33][34][35][36][37]57,58 commercially available biomedical grade segmented PU by wet spinning method, which has potential as a fiber for artificial vascular graft. 28 The small-diameter tubular artificial vascular graft was prepared from the HFIP solutions of SF-biomedical grade segmented PU mixture by electrospinning method by us.…”

“…The electrospinning methods have been used widely for the application of the SF-PU composite materials in biomedical field. 13,[29][30][31][32] The SF-PU composite films were also prepared by physical blending method. 25,[34][35][36][37]58 The characterization of the SF-PU composite materials by FT-IR and X-ray diffraction analyses suggested that there are no specific interactions between SF and PU, implying molecular immiscibility and phase separation in these materials.…”

“…So far, there are many papers about SF‐PU composite materials to use them as biomaterials 13,25,28–37,57,58 . Liu et al prepared the elastic biofiber with SF and commercially available biomedical grade segmented PU by wet spinning method, which has potential as a fiber for artificial vascular graft 28 .…”

“…However, there are no reports to clarify the origin from viewpoint of the structure and dynamics of the composite fibers in molecular level experimentally although many papers have been reported about SF-PU composite fibers and films. [25][26][27][28][29][30][31][32][33][34][35][36][37] We studied the origin using solid-state NMR. As the newly synthesized PU to prepare SF-PU composite material, we synthesized PU samples by direct mixing of isophorone diisocyanate (IPDI) as diisocyanate and poly (butylene adipate) (PBA) as dialcohol by two-step polyaddition process [18][19][20] because the IPDI and PBA units are considered to be nontoxic and biosafe, and therefore suitable to the use for biomaterials.…”

“…It is important to clarify the origin of the higher strength and higher elasticity of the SF‐PU composite fibers together with characterization of newly synthesized PU in molecular level. However, there are no reports to clarify the origin from viewpoint of the structure and dynamics of the composite fibers in molecular level experimentally although many papers have been reported about SF‐PU composite fibers and films 25–37 . We studied the origin using solid‐state NMR.…”