RESUMO
Vascular grafts are used as vascular access for hemodialysis, the most common renal replacement therapy to artificially clean blood waste after kidney malfunction. Despite that they are widely used in clinical practice, upon implantation, synthetic vasculars show complications such as thrombogenesis, reduced patency rates, low blood pressure, or even complete collapse. In this study, a C-shaped vascular graft was manufactured with small intestinal submucosa (SIS) and modified on the surface and the bulk of the material via conjugation of polyethylene glycol (PEG) to obtain a biocompatible and less thrombogenic vascular graft than the commercially available polytetrafluoroethylene (ePTFE) vascular grafts. Molecular weight and concentration of PEG molecules were systematically varied to gain insights into the underlying structure-function relationships. We analyzed the chemical, thermal, and mechanical properties of vascular grafts modified with 6 equiv of SIS-PEG 400 as well as cytotoxicity and in vitro platelet deposition. Immune response, patency rates, and extent of regeneration were also tested in vivo with the aid of swine animal models. Results showed that the conjugation levels achieved were sufficient to improve graft compliance, therefore approaching that of native vessels, while platelet deposition was altered leading to a 95% reduction compared with pristine SIS and 92% with respect to ePTFE. H&E staining on explanted samples corroborated SIS-PEG 400 biocompatibility and the ability to promote regeneration. The obtained results set solid foundations for the rational design and manufacture of a regenerative, small diameter vascular graft model and introduce an alternative to ePTFE vascular grafts for hemodialysis access.
RESUMO
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.