Design and Evaluation of a Structural Reinforced Small Intestinal Submucosa Vascular Graft for Hemodialysis Access in a Porcine Model

Abstract

Synthetic vascular access for hemodialysis exhibits biological and mechanical material properties mismatch with the native vessels. These limitations prevent infiltration of endothelial cells and decrease grafts long-term patency, particularly in small diameter vessels. We aimed to design a curved structural reinforced small intestinal submucosa (SIS) vascular graft for hemodialysis access and to evaluate in a porcine animal model graft patency by Doppler ultrasonography, tissue remodeling by histology, and vascular wall Young's modulus after implantation by biaxial tensile test. Curved 4 mm inner diameter, 0.5 mm thickness, and 150 mm length SIS grafts were designed. Small intestinal submucosa vascular grafts were preliminary tested in vivo in a porcine animal model (n=3) constructing an arteriovenous fistula between the carotid artery and the jugular vein; GORE-TEX grafts were implanted as control. Small intestinal submucosa grafts remained patent 46 ± 7 days against the control, 30 ± 3 days. Histology showed thrombus formation on the lumen (80% to 100% surface area) of all explanted grafts. Small intestinal submucosa grafts exhibited neovascularization and endothelial cells alignment on the graft wall, indicating regeneration. Biaxial tensile tests demonstrated no significant differences in Young's moduli between SIS grafts (ECirc = 2.5 ± 1.0 MPa, ELong = 5.7 ± 2.6 MPa) and native artery (ECirc = 1.4 ± 0.8 MPa, ELong = 5.5 ± 1.1 MPa), indicating similar wall stiffness. This study proposes an innovative design of a tissue-engineered vascular graft for hemodialysis access that, besides its structural characteristics similar to those of current synthetic grafts, could enhance biological performance because of its composition.

In vivo evaluation of an elastomeric small‐diameter vascular graft reinforced with a highly flexible Nitinol mesh

“…In addition, this study demonstrated that ultrasound techniques can be used to quantify and monitor highly informative morphological (diameter) and functional (compliance and blood flow velocity) graft parameters in an experimental model in which the natural vessel is replaced with a synthetic one. This overcomes the typical use of the ultrasound Doppler which is limited to test the vessel patency . Furthermore, the noninvasive nature of the ultrasound will allow planning future studies in which the animals’ sacrifice is replaced by a multiple time point analysis, in order to reduce the total number of animals required to reach satisfactory statistical power for the study.…”

Evaluation of Microscopic Structure−Function Relationships of PEGylated Small Intestinal Submucosa Vascular Grafts for Arteriovenous Connection

“…For this study, samples were cut into test pieces for chemical, thermal, mechanical, and microscopy assays or stored in plastic containers for sterilization with ethylene oxide for in vivo testing. Mechanical stability and proper sealing of rolled tubes were previously demonstrated both in vitro and in vivo. ,, …”

“…Mechanical stability and proper sealing of rolled tubes were previously demonstrated both in vitro and in vivo. 13,14,19 Conjugation. Once the grafts were formed and completely dried, polyethylene glycol (PEG) was conjugated on the surface and the bulk of the material.…”

Hemodynamics and Wall Mechanics of Vascular Graft Failure

“…[121][122][123][124] Planar biaxial devices that test samples from the graft wall with the residual stress relieved by a longitudinal cut have also been used. 125,126 Kink resistance and suture retention can be tested experimentally to limit catastrophic failure due to anastomotic failure or graft occlusion during surgical handling. 122,127 In vitro tests also yield important insights on the hemodynamics underlying vascular graft failure, particularly with the use of benchtop systems to characterize flow in different types of vascular grafts.…”