Decreased Platelet Deposition in SIS-Based Vascular Grafts via Covalent Conjugation of RAFT Polymers

Valencia-Rivero, Karen T.; Cruz, Juan C.; Briceño, Juan Carlos; DrAmore, Antonio; Ye, Sang‐Ho; Geest, Jonathan Vande; Wagner, William R.

doi:10.1109/sib.2018.8467727

Cited by 1 publication

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“…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.…”

Section: ■ Experimental Sectionmentioning

confidence: 99%

“…Image analysis was conducted in MATLAB with a custom-made script that correlates pressure changes in the sensor with volume changes detected in the images. 14 To study suture retention strength, a biaxial stress instrument (TESTBENCH, TA Instruments (DE), USA) was adjusted in a uniaxial setting, to evaluate the resistance of the grafts against the pull-out of a suture loop (prolene 5−0). WinTest 4.1 software was used to displace the motor of the instrument, remove the preload in the samples, and record the force before the suture was pulled out of the sample.…”

Section: ■ Experimental Sectionmentioning

confidence: 99%

“…Platelet deposition and cytotoxicity in pristine and PEGylated SIS samples were analyzed in vitro using ePTFE samples as control group. 14 Lactate dehydrogenase assay (LDH) and SEM were also carried out to study platelet deposition. For LDH, samples were immersed in whole ovine blood for 1.5 h at 37 °C under continuous rocking.…”

Section: ■ Experimental Sectionmentioning

confidence: 99%

“…13 SIS vascular grafts show, however, very limited long-term patency rates, which have been primarily attributed to their high collagen content (around 67%). 14 This, in turn, is known to promote platelet deposition and eventually thrombus formation. Based on the results obtained with pristine SIS on regeneration, we wanted to improve the SIS-based vascular grafts with its PEGylation to reduce platelet deposition and avoid thrombus formation, given that an ample body of literature showed that PEGylation is effective in reducing immunogenicity, immunotoxicity, and hepatotoxicity in vivo.…”

Section: Introductionmentioning

confidence: 99%

“…Previous studies reported the implementation of SIS vascular grafts for short-term arteriovenous connections for hemodialysis with exceptional vascular regeneration and short-term patency rates in vivo that even exceeded those obtained with commercially available ePTFE vascular grafts . SIS vascular grafts show, however, very limited long-term patency rates, which have been primarily attributed to their high collagen content (around 67%) . This, in turn, is known to promote platelet deposition and eventually thrombus formation.…”

Section: Introductionmentioning

confidence: 99%

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

Valencia-Rivero

Cruz

Wagner-Gutierrez

et al. 2019

ACS Appl. Bio Mater.

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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.

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Section: ■ Experimental Sectionmentioning

confidence: 99%

Section: ■ Experimental Sectionmentioning

confidence: 99%

Section: ■ Experimental Sectionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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