A Reproducible Porcine ePTFE Arterial Bypass Model for Neointimal Hyperplasia

Kapadia, Muneera R.; Aalami, Oliver; Najjar, Samer F.; Jiang, Qun; Murar, Jozef; Lyle, Brian; Eng, Jason W.-L.; Kane, Bonnie J.; Carroll, Timothy J.; Cahill, Patricia M.; Kibbe, Melina R.

doi:10.1016/j.jss.2007.08.003

Cited by 6 publications

(4 citation statements)

References 24 publications

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“…For the purpose of this animal study, we previously established that porcine ECs are able to attach and grow on cRRE surfaces to the same degree as human ECs, making pigs the most appropriate model to evaluate the FSP-coated ePTFE grafts 29 . The porcine carotid artery model required that the grafts be implanted with a slightly curved configuration, a model used in other studies 30 , since an early attempt at a straight graft during model development did not allow the pig enough movement in the neck region and resulted in anastomotic tearing and hemorrhage. A slightly curved configuration may lead to hemodynamic perturbations distal to the graft; however, the result should be consistent across all grafts since they were similar.…”

Section: Discussionmentioning

confidence: 99%

In vivo evaluation of biomimetic fluorosurfactant polymer-coated expanded polytetrafluoroethylene vascular grafts in a porcine carotid artery bypass model

Bastijanic

Marchant

Kligman

et al. 2016

Journal of Vascular Surgery

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Objective To evaluate the potential for biomimetic self-assembling fluorosurfactant polymer (FSP) coatings incorporating either heptamaltose (M7-FSP) to block non-specific protein adsorption, the cell adhesive RGD peptide (RGD-FSP), or the endothelial cell-selective CRRETAWAC peptide (cRRE-FSP) to improve patency and endothelialization in small diameter ePTFE vascular graft implants. Methods ePTFE vascular grafts (4 mm diameter, 5 cm length) were coated with either M7-FSP, RGD-FSP, or cRRE-FSP by dissolving FSPs in distilled water and flowing solution through the graft lumen for 24 h. Coatings were confirmed by receding water contact angle measurements on the lumen surface. RGD-FSP and cRRE-FSP grafts were pre-sodded in vitro with porcine pulmonary artery endothelial cells (PPAECs) using a custom-designed flow system. PPAEC coverage on the lumen surface was visualized with epifluorescent microscopy and quantified. Grafts were implanted as carotid artery interposition bypass grafts in 7 pigs for 33 ± 2 days (ePTFE n=3, M7-FSP n=4, RGD-FSP n=3, cRRE-FSP n=4). Patency was confirmed immediately after implant with duplex color-flow ultrasound and at explant with contrast-enhanced angiography. Grafts were sectioned for histology and stained: Movat’s pentachrome stain to outline vascular layers; immunofluorescent staining to identify endothelial cells (anti-von Willebrand factor antibody) and immunohistochemical staining to identify smooth muscle cells (anti-smooth muscle α-actin antibody). Neoinitima:lumen area ratio was determined to evaluate neointimal hyperplasia. Results Receding water contact angle measurements on graft luminal surfaces were significantly lower (P < .05) on FSP-coated ePTFE surfaces (M7-FSP: 40 ± 16°, RGD-FSP: 25 ± 10°, cRRE-FSP: 33 ± 16°) compared to uncoated ePTFE (126 ± 2°), confirming presence of the FSP layer. In vitro sodding of PPAECs on RGD-FSP and cRRE-FSP grafts resulted in a confluent monolayer of PPAECs on the luminal surface, with similar cell population on RGD-FSP (1200 ± 187 cells/mm2) and cRRE-FSP (1134 ± 153 cells/mm2) grafts. All grafts were patent immediately after implant, and 1/3 uncoated, 2/3 RGD-FSP, 2/4 M7-FSP, and 2/4 cRRE-FSP grafts remained patent after 1 month. PPAEC coverage of the lumen surface was seen in all patent grafts. RGD-FSP grafts had a slightly higher neointima:lumen area ratio (0.53 ± 0.06) compared to uncoated (0.29 ± 0.15), M7-FSP (0.20 ± 0.15), or cRRE-FSP (0.17 ± 0.09) grafts. Conclusion Biomimetic FSP coated ePTFE grafts can be utilized successfully in vivo and have potential to support endothelialization. Grafts modified with the M7-FSP and cRRE-FSP showed lower intimal hyperplasia compared to RGD-FSP grafts.

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Section: Discussionmentioning

confidence: 99%

In vivo evaluation of biomimetic fluorosurfactant polymer-coated expanded polytetrafluoroethylene vascular grafts in a porcine carotid artery bypass model

Bastijanic

Marchant

Kligman

et al. 2016

Journal of Vascular Surgery

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“…These findings represent a significant step forward for the intravascular use of this novel biodegradable material in humans, as the coated grafts were not associated with any negative tissue response. The animal model used was based on a previously established porcine model of prosthetic bypass grafting that results in reproducible neointimal hyperplasia 20…”

Section: Discussionmentioning

confidence: 99%

“…Details of the animal model have been previously published 20. Briefly, animals were placed in the supine position, and their necks were shaved then prepped with betadine and alcohol (70%).…”

Section: Methodsmentioning

confidence: 99%

Citric acid‐based elastomers provide a biocompatible interface for vascular grafts

Kibbe

Martinez²,

Popowich³

et al. 2009

J Biomedical Materials Res

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Prosthetic vascular bypass grafting is associated with poor long-term patency rates. Herein, we report on the mid-term performance of expanded polytetrafluoroethylene (ePTFE) vascular grafts modified with a citric acid-based biodegradable elastomer. Through a spin-shearing method, ePTFE grafts were modified by mechanically coating a layer of poly(1,8 octanediol citrate) (POC) onto the luminal nodes and fibrils of the ePTFE. Control and POC-ePTFE grafts were implanted into the porcine carotid artery circulation as end-to-side bypass grafts. Grafts were assessed by duplex ultrasonography, magnetic resonance angiography, and digital subtraction contrast angiography and were all found to be patent with no hemodynamically significant stenoses. At 4 weeks, POC-ePTFE grafts were found to be biocompatible and resulted in a similar extent of neointimal hyperplasia as well as leukocyte and monocyte/macrophage infiltration as control ePTFE grafts. Furthermore, POC supported endothelial cell growth. Lastly, scanning electron microscopy confirmed the presence of POC on the ePTFE grafts at 4 weeks. Thus, these data reveal that surface modification of blood-contacting surfaces with POC results in a biocompatible surface that does not induce any untoward effects or inflammation in the vasculature. These findings are important as they will serve as the foundation for the development of a drug-eluting vascular graft.

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“…In recent studies, synthetic grafts completely devoid of cells have been attempted. However, the problem of neointimal hyperplasia could not be overcome [9]. Two recent studies showed that TEVs lacking cells in the vascular wall could be implanted into the venous system of mice [10] or the abdominal aorta of rats [11].…”

Section: Introductionmentioning

confidence: 99%

Arterial grafts exhibiting unprecedented cellular infiltration and remodeling in vivo: The role of cells in the vascular wall

et al. 2015

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Objective To engineer and implant vascular grafts in the arterial circulation of a pre-clinical animal model and assess the role of donor medial cells in graft remodeling and function. Approach and results Vascular grafts were engineered using Small Intestinal Submucosa (SIS)-fibrin hybrid scaffold and implanted interpositionally into the arterial circulation of an ovine model. We sought to demonstrate implantability of SIS-Fibrin based grafts; examine the remodeling; and determine whether the presence of vascular cells in the medial wall was necessary for cellular infiltration from the host and successful remodeling of the implants. We observed no occlusions or anastomotic complications in 18 animals that received these grafts. Notably, the grafts exhibited unprecedented levels of host cell infiltration that was not limited to the anastomotic sites but occurred through the lumen as well as the extramural side, leading to uniform cell distribution. Incoming cells remodeled the extracellular matrix and matured into functional smooth muscle cells as evidenced by expression of myogenic markers and development of vascular reactivity. Interestingly, tracking the donor cells revealed that their presence was beneficial but not necessary for successful grafting. Indeed, the proliferation rate and number of donor cells decreased over time as the vascular wall was dominated by host cells leading to significant remodeling and development of contractile function. Conclusions These results demonstrate that SIS-Fibrin grafts can be successfully implanted into the arterial circulation of a clinically relevant animal model, improve our understanding of vascular graft remodeling and raise the possibility of engineering mural cell-free arterial grafts.

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A Reproducible Porcine ePTFE Arterial Bypass Model for Neointimal Hyperplasia

Cited by 6 publications

References 24 publications

In vivo evaluation of biomimetic fluorosurfactant polymer-coated expanded polytetrafluoroethylene vascular grafts in a porcine carotid artery bypass model

In vivo evaluation of biomimetic fluorosurfactant polymer-coated expanded polytetrafluoroethylene vascular grafts in a porcine carotid artery bypass model

Citric acid‐based elastomers provide a biocompatible interface for vascular grafts

Arterial grafts exhibiting unprecedented cellular infiltration and remodeling in vivo: The role of cells in the vascular wall

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