The Use of Antithrombotic Therapies in Reducing Synthetic Small-Diameter Vascular Graft Thrombosis

Tatterton, Mark; Wilshaw, Stacy‐Paul; Ingham, Eileen; Homer‐Vanniasinkam, Shervanthi

doi:10.1177/1538574411433299

Cited by 46 publications

(40 citation statements)

References 110 publications

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“…Although a comprehensive reviewof all antithrombogenic strategies for cardiovascular biomaterials is beyond the scope of this current paper, Table 1 provides a summary of heparin-modification strategies and current technologies that are specific to the development of vascular graft biomaterials. A more detailed review of antithrombogenic coating technologies for vascular grafts has been prepared by Tatterton et al, and Kapadia et al [38,39]. In recent years, there has been a growth of commercially available heparinmodified vascular graft materials such as the Propaten ® graft (W.L.…”

Section: Discussionmentioning

confidence: 99%

The blood and vascular cell compatibility of heparin-modified ePTFE vascular grafts

et al. 2013

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Prosthetic vascular grafts do not mimic the antithrombogenic properties of native blood vessels and therefore have higher rates of complications that involve thrombosis and restenosis. We developed an approach for grafting bioactive heparin, a potent anticoagulant glycosaminoglycan, to the lumen of ePTFE vascular grafts to improve their interactions with blood and vascular cells. Heparin was bound to aminated poly(1,8-octanediol-co-citrate) (POC) via its carboxyl functional groups onto POC-modified ePTFE grafts. The bioactivity and stability of the POC-immobilized heparin (POC–Heparin) were characterized via platelet adhesion and clotting assays. The effects of POC–Heparin on the adhesion, viability and phenotype of primary endothelial cells (EC), blood outgrowth endothelial cells (BOECs) obtained from endothelial progenitor cells (EPCs) isolated from human peripheral blood, and smooth muscle cells were also investigated. POC–Heparin grafts maintained bioactivity under physiologically relevant conditions in vitro for at least one month. Specifically, POC–Heparin-coated ePTFE grafts significantly reduced platelet adhesion and inhibited whole blood clotting kinetics. POC–Heparin supported EC and BOEC adhesion, viability, proliferation, NO production, and expression of endothelial cell-specific markers von Willebrand factor (vWF) and vascular endothelial-cadherin (VE-cadherin). Smooth muscle cells cultured on POC–Heparin showed increased expression of α-actin and decreased cell proliferation. This approach can be easily adapted to modify other blood contacting devices such as stents where antithrombogenicity and improved endothelialization are desirable properties.

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Section: Discussionmentioning

confidence: 99%

The blood and vascular cell compatibility of heparin-modified ePTFE vascular grafts

et al. 2013

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“…However, the problem of early failure is a serious clinical problem [9][10][11] . Since not only the problem of small-caliber vascular conduits must be considered, but the question of biomechanical tissue remodeling is also a key factor with all the shear stress-,…”

Section: Discussionmentioning

confidence: 99%

“…The number of prosthetic grafts, used for intermittent claudication/critical limb ischemia has fallen. Poor patency rate and the concerns about graft infections are the main reasons for that [1][2][3][4][5][9][10][11][12][13] .…”

Section: Introductionmentioning

confidence: 99%

“…Late: pseudoaneurysm formation due to suture insufficiency, obstruction of the graft, stenosis caused by neointima formation or occlusion, graft infection [9][10][11][12][13] . The blood flow characteristics change at the anastomoses, the cells may suffer mechanical injury -here the formation of deposits usually leads to another operation 10,[12][13][14] .…”

Section: Introductionmentioning

confidence: 99%

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Early postoperative changes in hematological, erythrocyte aggregation and blood coagulation parameters after unilateral implantation of polytetrafluoroethylene vascular graft in the femoral artery of beagle dogs

et al. 2014

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PURPOSE:The failure of small-caliber vascular grafts still means a serious problem. Concerning the early postoperative complications we aimed to investigate the hemostaseological and hemorheological aspects of this issue in a canine model. METHODS:In the Control group only anesthesia was induced. In the Grafted group under general anesthesia a 3.5-cm segment was resected unilaterally from the femoral artery and replaced with a PTFE graft (diameter: 3 mm). On the 1 st -3 rd -5 th -7 th and 14 th postoperative days the skin temperature of both hind limbs was measured, and blood sampling occurred for hematological, hemostaseological and hemorheological tests. RESULTS:The skin temperature of the operated versus intact limbs did not differ. In the Grafted group leukocyte count was elevated by the 1 st postoperative day, while platelet count increased over the entire follow-up period. Fibrinogen concentration rose on the 1 st -5 th days, activated partial thromboplastin time increased on the 3 rd -7 th days. Erythrocyte aggregation was enhanced significantly on the 1 st -5 th days. In specimens taken on the 14 th day, histologically we found matured thrombus narrowing the graft lumen. CONCLUSIONS:Small-caliber PTFE graft implantation into the femoral artery caused significant changes in several hemostaseological and hemorheological parameters. However, better clarifying the factors leading to early thrombosis of these grafts needs further studies.Key words: Vascular Grafting. Graft Occlusion, Vascular. Erythrocyte Aggregation. Blood Coagulation. Models, Animal. Dogs. Early postoperative changes in hematological, erythrocyte aggregation and blood coagulation parameters after unilateral implantation of polytetrafluoroethylene vascular graft in the femoral artery of beagle dogs

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“…26 In addition, heparin also offered a negative-charged surface to block the interaction between platelets and scaffolds by electrostatic repulsion, 10 thus contributing to the prevention of thrombotic occlusion.…”

Section: Discussionmentioning

confidence: 99%

Fabrication of small-diameter vascular scaffolds by heparin-bonded P(LLA-CL) composite nanofibers to improve graft patency

Wang¹,

Mo²,

Jiang³

et al. 2013

IJN

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Abstract:The poor patency rate following small-diameter vascular grafting remains a major hurdle for the widespread clinical application of artificial blood vessels to date. Our previous studies found that electrospun poly(L-lactide-co-epsilon-caprolactone) (P[LLA-CL]) nanofibers facilitated the attachment and growth of endothelial cells (EC), and heparin incorporated into P(LLA-CL) nanofibers was able to release in a controlled manner. Hence, we hypothesized that heparin-bonded P(LLA-CL) vascular scaffolds with autologous EC pre-endothelialization could significantly promote the graft patency rate. To construct a small-diameter vascular scaffold, the inner layer was fabricated by heparin-bonded P(LLA-CL) nanofibers through coaxial electrospinning, while the outer layer was woven by pure P(LLA-CL) nanofibers. Except dynamic compliance (5.4 ± 1.7 versus 12.8 ± 2.4 × 10 −4 /mmHg, P , 0.05), maximal tensile strength, burst pressure, and suture retention of the composite, scaffolds were comparable to those of canine femoral arteries. In vitro studies indicated that the scaffolds can continuously release heparin for at least 12 weeks and obtain desirable endothelialization through dynamic incubation, which was confirmed by EC viability and proliferation assay and scanning electronic microscopy. Furthermore, in vivo studies demonstrated that pre-endothelialization by autologous ECs provided a better effect on graft patency rate in comparison with heparin loading, and the united application of pre-endothelialization and heparin loading markedly promoted the 24 weeks patency rate of P(LLA-CL) scaffolds (88.9% versus 12.5% in the control group, P , 0.05) in the canine femoral artery replacement model. These results suggest that heparin-bonded P(LLA-CL) scaffolds have similar biomechanical properties to those of native arteries and possess a multiporous and biocompatible surface to achieve satisfactory endothelialization in vitro. Heparin-bonded P(LLA-CL) scaffolds with autologous EC pre-endothelialization have the potential to be substitutes for natural small-diameter vessels in planned vascular bypass surgery.

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The Use of Antithrombotic Therapies in Reducing Synthetic Small-Diameter Vascular Graft Thrombosis

Abstract: Very few antithrombotic therapies have translated into clinical use. More human in vivo studies are required to assess the efficacy and safety of such therapies.

Cited by 46 publications

References 110 publications

The blood and vascular cell compatibility of heparin-modified ePTFE vascular grafts

The blood and vascular cell compatibility of heparin-modified ePTFE vascular grafts

Early postoperative changes in hematological, erythrocyte aggregation and blood coagulation parameters after unilateral implantation of polytetrafluoroethylene vascular graft in the femoral artery of beagle dogs

Fabrication of small-diameter vascular scaffolds by heparin-bonded P(LLA-CL) composite nanofibers to improve graft patency

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