Abstract

BackgroundSynthetic expanded polytetrafluorethylene (ePTFE) grafts are routinely used for vascular repair and reconstruction but prone to sustained bacterial infections. Investigational bioengineered human acellular vessels (HAVs) have shown clinical success and may confer lower susceptibility to infection. Here we directly compared the susceptibility of ePTFE grafts and HAV to bacterial contamination in a preclinical model of infection. Materials and methodsSections (1 cm2) of ePTFE (n = 42) or HAV (n = 42) were inserted within bilateral subcutaneous pockets on the dorsum of rats and inoculated with Staphylococcus aureus (107 CFU/0.25 mL) or Escherichia coli (108 CFU/0.25 mL) before wound closure. Two weeks later, the implant sites were scored for abscess formation and explanted materials were halved for quantification of microbial recovery and histological analyses. ResultsThe ePTFE implants had significantly higher abscess formation scores for both S. aureus and E. coli inoculations compared to that of HAV. In addition, significantly more bacteria were recovered from explanted ePTFE compared to HAV. Gram staining of explanted tissue sections revealed interstitial bacterial contamination within ePTFE, whereas no bacteria were identified in HAV tissue sections. Numerous CD45+ leukocytes, predominantly neutrophils, were found surrounding the ePTFE implants but minimal intact neutrophils were observed within the ePTFE matrix. The host cells surrounding and infiltrating the HAV explants were primarily nonleukocytes (CD45−). ConclusionsIn an established animal model of infection, HAV was significantly less susceptible to bacterial colonization and abscess formation than ePTFE. The preclinical findings presented in this manuscript, combined with previously published clinical observations, suggest that bioengineered HAV may exhibit low rates of infection.

Highlights

  • Synthetic vascular grafts have provided life and limbesustaining therapy for millions of patients as both arterial bypass conduits and dialysis access grafts

  • Quantification of microbial recovery was assessed in 79 of the 84 samples because two explanted samples were inadvertently fixed in formalin, and three human acellular vessels (HAVs) samples within the E. coli group were not found within the bisected half of the explanted tissue designated for microbial recovery processing

  • We subsequently examined the other halves of the tissue from these three HAV explants that were fixed for histological analysis

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Summary

Introduction

Synthetic vascular grafts have provided life and limbesustaining therapy for millions of patients as both arterial bypass conduits and dialysis access grafts This technology has been useful for many years, one of its frequent failure modes in the clinic is that of bacterial colonization and infection.[1,2,3] Following implantation and hemodialysis access, it has been reported that as many as 28% of synthetic vascular grafts,[4] such as those constructed from expanded polytetrafluorethylene (ePTFE), will require revision or explant due to infection, which significantly impacts medical costs and patient morbidity.[5,6] It has been suggested that the microporous structure and synthetic composition of ePTFE grafts provide niches for bacterial accumulation[7] and interferes with the ability of host leukocytes to combat bacterial infections.[8,9]. Routine vascular access for hemodialysis presents an inherent infection risk due to potential introduction of bacteria during cannulation This can lead to local infection of the vascular grafts and surrounding tissue and bacteremia and sepsis.

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