ePTFE Grafts Research Articles

Thrombotic Ringed Polytetrafluoroethylene Graft With Infection After Living-Donor Liver Transplantation

BackgroundThe safety of the living donor in living-donor liver transplantation (LDLT) is always the first priority, meanwhile, the graft-to-recipient weight ratio (GRWR) and the anatomy of the liver allograft must also not be compromised in order to warrant tranplatation success. When it comes to the allograft of the right lobe of the liver without the middle hepatic vein (R–M), the outflow and adequate drainage for the territory of middle hepatic vein (MHV) is one critical concern. Despite publications in some high-volume transplant centers on the positive results of using expanded polytetrafluoroethylene (ePTFE) grafts to substitute those of autologous veins, complications related to the ePTFE graft have not been well discussed. MethodsFrom July 2012 to June 2016, 129 adult patients who underwent living donor liver transplantation in Taipei Veterans General Hospital were analyzed. There were 3 cases of adjacent organ erosion with gas bubbles in the lumen of an ePTFE graft, including gastrointestinal (GI) tract penetration in 2 out of the first 15 cases that used the venous graft of ringed expanded polytetrafluoroethylene (rPTFE). The patient survival rate during this period was compared and radiological findings of rPTFE function and clinical signs of erosion with infection were also examined to raise the concerns of safety as well as early detection of complications of rPTFE. ResultsThe overall 1-year patient survival rate was 90%, of which the right lobe wih MHV (R+M) group was 93.5% and the R–M group was 91.9%. For the mean of GRWR, the R+M group was 1.05 ± 0.19 and R–M group was 1.19 ± 0.27, while those who needed reconstruction with vein grafts was 0.96 ± 0.11. Among the R–M group, 24 out of 88 cases (27.3%) needed reconstruction of MHV tributaries. Of the 24 cases, 15 cases were done with rPTFE and the 1-year patient survival rate of the rPTFE group was 73%, which is significantly worse (P = .008) than the non-rPTFE (89%) and non-reconstructed (97%) groups. The mean GRWR is significantly higher (P = .001) in the non-reconstructed group (1.19 ± 0.27) than in the rPTFE (0.99 ± 0.11) and non-rPTFE (0.94 ± 0.11) groups. The venous grafts patency rate between the different graft types is no different, and there is also significance in warm ischemic time (P = .009) between the non-reconstructed (49 ± 15), rPTFE (81 ± 51), and non-rPTFE (56 ± 18) groups in the mean minutes. ConclusionIn cases of fever of unknown cause in patients receiving LDLT with rPTFE graft, a regular computed tomography (CT) scan with contrast and gas bubbles within the graft lumen is the best way for early detection of graft related infection and suspicious GI tract penetration. To decrease the risks of tissue reaction induced by ePTFE graft in LDLT, omentum patches or other inert agents can be introduced as a buffer between the graft and adjacent organs, especially the GI tracts. However, research in material science shall be explored to solve the problem in the future.

Polyurethane/polyurethane nanoparticle‐modified expanded poly(tetrafluoroethylene) vascular patches promote endothelialization

Expanded poly(tetrafluoroethylene) (ePTFE) has been widely used as a vascular graft material due to the fact that it is durable, porous, flexible, and inert. However, ePTFE grafts easily induce thrombosis, calcification and neointimal hyperplasia in small-diameter (<6 mm) graft bypass surgeries and thus cause surgical failure. Therefore, it is necessary to improve the in vitro and in vivo performances of ePTFE grafts. In this work, we first prepared a polyurethane/polyurethane nanoparticles (PU/PU-NPs) composite film by a simple cosedimentation method. Compared with the pure PU film, the blood compatibility and the cell compatibility of the PU/PU-NPs composite film were significantly improved. Then, we constructed a PU/PU-NPs/ePTFE vascular patch (PPVP) by coating PU and PU-NPs onto the surface of an ePTFE graft. PU-NP modification endowed the ePTFE graft with the nanopatterned surface similar to the luminal surface of a blood vessel. PU NPs and the structural likeness of the surface synergistically optimized the overall performance, and thus improved the blood and cell compatibilities, effectively inhibited platelet adhesion, enhanced cell attachment and proliferation, and facilitated the formation of endothelial tissue-endothelialization. The abdominal artery patched with PPVP was not blocked and the endothelialization was achieved 30 days after the implantation. All the results taken together indicate that PPVP may be a promising alternative for a vascular patch. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 2131-2140, 2018.

Improved Patency of ePTFE Grafts as a Hemodialysis Access Site by Seeding Autologous Endothelial Cells Expressing Fibulin-5 and VEGF.

Small caliber synthetic vascular grafts used for dialysis access sites have high failure rates due to neointima formation andthrombosis. Seeding synthetic grafts with endothelial cells (ECs) provides a biocompatible surface that may prevent graft failure. We tested the use of ePTFE grafts seeded with autologous ECs expressing fibulin-5 and vascular endothelial growth factor (VEGF), as a dialysis access site in a porcine model. We connected the carotid arteries and jugular veins of 12miniature pigs using 7-mm ePTFE grafts; five grafts were seeded with autologous venous ECs modified to express fibulin-5 and VEGF, and seven unseeded grafts were implanted at the same location and served as controls. At 6months, after completion of angiography, the carotid arteries and jugular veins with the connecting grafts were excised and fixed. Autologous EC isolation and transduction and graft seeding were successful in all animals. At 3months, 4 of 5 seeded grafts and 3 of 7 control grafts were patent. At 6months, 4 of 5 (80%) seeded grafts and only 2 of 7 (29%) control grafts were patent. Seeding ePTFE vascular grafts with genetically modified ECs improved long term small caliber graft patency. The biosynthetic grafts offera novel therapeutic modality for vascular access in hemodialysis.

A prospective randomized study of bovine carotid artery biologic graft and expanded polytetrafluoroethylene for permanent hemodialysis access

ObjectiveArteriovenous grafts (AVGs) remain reliable substitutes for permanent hemodialysis access in scenarios that preclude the placement of native arteriovenous fistulas (AVFs). The majority of AVGs are constructed of expanded polytetrafluoroethylene (ePTFE), which is relatively inexpensive and readily available, but synthetic AVGs have poor patency rates. On the other hand, biologic grafts confer an advantage by virtue of their inherent similarity to the native human vasculature. However, evidence to support the current preference of synthetic conduits over biologic grafts in clinical practice is scarce. The aim of this protocol is to propose a contemporary re-evaluation and comparison between ePTFE and bovine carotid artery (BCA) grafts. MethodsThis prospective randomized controlled trial is being conducted at an academic hospital center. A total of 100 patients at least 18 years of age and undergoing AVG placement will be recruited and prospectively randomized into two parallel groups with a 1:1 allocation ratio. Patients eligible to receive AVF and those with a known allergic reaction or history of intolerance to any ePTFE or BCA component will not be included in the study. Moreover, patients with a recent active infection at the site of previous AVG placement and patients with a bleeding disorder, an active malignant disease, or a life expectancy <1 year or who refuse blood transfusion and pregnant women will be excluded. Patients will receive either BCA (experimental) or standard ePTFE grafts (control) in compliance with the National Kidney Foundation Kidney Disease Outcomes Quality Initiative guidelines for AVG creation. Primary end points include primary, primary assisted, secondary, and functional patency at 1 year and 2 years after graft placement. Secondary outcomes include complications (pseudoaneurysms, infections, and steal syndrome) and reintervention rates during the first and second postoperative years. Outcomes will be assessed and documented every 6 months. ResultsOnce the study is completed, analysis of the data will be performed using univariate methods, and Kaplan-Meier and multivariate Cox proportional regression analyses will be employed to evaluate and to compare outcomes between BCA and ePTFE over time. ConclusionsThe creation of a functional and durable dialysis vascular access is crucial in the treatment of patients with end-stage renal disease and is a challenging quest for vascular surgeons. The proposed study compares the outcomes of synthetic and biologic AVG options in patients who are poor candidates for a native AVF. This will help derive contemporary evidence and improve the care of vascular access patients.

Inhibiting intimal hyperplasia in prosthetic vascular grafts via immobilized all-trans retinoic acid

Peripheral arterial disease is a leading cause of morbidity and mortality. The most commonly utilized prosthetic material for peripheral bypass grafting is expanded polytetrafluoroethylene (ePTFE) yet it continues to exhibit poor performance from restenosis due to neointimal hyperplasia, especially in femoral distal bypass procedures. Recently, we demonstrated that periadventitial delivery of all-trans retinoic acid (atRA) immobilized throughout porous poly(1,8 octamethylene citrate) (POC) membranes inhibited neointimal formation in a rat arterial injury model. Thus, the objective of this study was to investigate whether atRA immobilized throughout the lumen of ePTFE vascular grafts would inhibit intimal formation following arterial bypass grafting. Utilizing standard ePTFE, two types of atRA-containing ePTFE vascular grafts were fabricated and evaluated: grafts whereby all-trans retinoic acid was directly immobilized on ePTFE (atRA-ePTFE) and grafts where all-trans retinoic acid was immobilized onto ePTFE grafts coated with POC (atRA-POC-ePTFE). All grafts were characterized by SEM, HPLC, and FTIR and physical characteristics were evaluated in vitro. Modification of these grafts, did not significantly alter their physical characteristics or biocompatibility, and resulted in inhibition of intimal formation in a rat aortic bypass model, with atRA-POC-ePTFE inhibiting intimal formation at both the proximal and distal graft sections. In addition, treatment with atRA-POC-ePTFE resulted in increased graft endothelialization and decreased inflammation when compared to the other treatment groups. This work further confirms the biocompatibility and efficacy of locally delivered atRA to inhibit intimal formation in a bypass setting. Thus, atRA-POC-ePTFE grafts have the potential to improve patency rates in small diameter bypass grafts and warrant further investigation.

A pilot study comparing bovine mesenteric artery and expanded polytetrafluoroethylene grafts as non-autogenous hemodialysis options.

Background Many dialysis patients do not have the necessary conditions for construction of a native arteriovenous fistula (AVF). Expanded Polytetrafluoroethylene (ePTFE) vascular prostheses are the most widely-used option, but it is known that they are inferior to native vein AVFs. Objectives To identify a graft with superior performance to ePTFE, comparing their results with those of AVFs made from bovine mesenteric arteries treated with L-Hydro technology (Labcor Laboratories ®). Methods A prospective and controlled study of 10 patients with AVFs constructed with ePTFE and 10 patients with L-Hydro bioprostheses, matched for comorbidities. The variables studied were: primary patency, assisted primary patency, and secondary patency, surgical manipulability, and prevalence of infections. The performance of prostheses was assessed by duplex-scan and repeated consultations with health professionals at hemodialysis clinics. The chi-square test was used for statistical analysis. Results After 1 year of postoperative follow-up, secondary and primary patency rates were higher for L-Hydro than ePTFE AVFs. Fewer interventions were needed to maintain AVF patency in the L-Hydro AVF group. The most common complication was graft thrombosis, which was more frequent in the ePTFE group. While the figures indicate more favorable outcomes in the L-Hydro AVFs, this could not be confirmed with the statistical treatment employed. Conclusions The L-Hydro graft appears to be a valuable alternative option for AVFs, since it seems to require fewer interventions to maintain patency when compared to ePTFE grafts.

Engineered Blood Vessels

The field of tissue engineering has has made significant progress in the past 20 years. Of the many tissues and organs in development, the area of vascular tissue engineering is now one of the most mature. In that regard, we have developed a novel tissue engineered vascular graft (human acellular vessel [HAV]) that addresses many of the limitations of native vein harvest and the performance of both synthetic ePTFE and autologous vein grafts. The HAV is manufactured in a laboratory by culturing human vascular cells within a biodegradable scaffold that forms a mechanically robust tissue engineered blood vessel. The cells are then completely removed (decellularization), leaving behind a non-immunogenic human collagen-based vascular tissue that can be stored on the shelf for months at a time and ready for immediate implantation into any patient. The HAV is currently being evaluated in Phase II and Phase III clinical trials in the U.S., E.U. and Israel as an arteriovenous vascular access graft for hemodialysis in patients with end-stage renal failure and as an arterial substitute for patients in need of vascular bypass for peripheral arterial disease or vascular trauma. Following clinical implantation, we have observed repopulation and remodeling of the manufactured vessel with the hosts' own cells. We hypothesize that the biological composition of the HAV, compared to synthetic vascular grafts, promotes its physiological integration into host tissue including support of normal host cell infiltration and function. Host cells that identify histologically similar to vascular smooth muscle cells appear to repopulate the middle of the vessel and recipient cells characterized as endothelial cells appear to cover the luminal surface of the implanted vessel. Clinical observations of the Phase II trials have demonstrated excellent vessel durability and a freedom from both early and delayed infection. Based on the success of the Phase II studies, a Global Phase III study is underway for patients in need of dialysis access shunts and vascular programs for vascular (arterial) bypass and trauma are expanding. DisclosuresLawson:InnaVasc: Patents & Royalties; Humacyte, Inc.: Employment.

Sustained Thromboresistant Bioactivity with Reduced Intimal Hyperplasia of Heparin-Bonded Polytetrafluoroethylene Propaten Graft in a Chronic Canine Femoral Artery Bypass Model

Bypass graft thrombosis remains a significant mode of failure in prosthetic graft revascularization. The purpose of this investigation was to evaluate the long-term thromboresistant effect of heparin-bonded expanded polytetrafluoroethylene (ePTFE) graft using Carmeda BioActive Surface technology in a canine model. Bilateral femorofemoral artery bypass grafts with ePTFE grafts were performed in 25 adult grayhound dogs. In each animal, a heparin-bonded ePTFE graft (Propaten, WL Gore) was placed on one side, whereas a control nonheparin graft was placed on the contralateral side. The graft patency was assessed at 1, 6, 12, 18, and 24months (n=5 per group) following the bypass. Heparin bioactivity of the graft material was analyzed. The effect of intimal hyperplasia was also assessed. All bypass grafts were patent at 1 month. Significantly greater patency rates were noted in the Propaten group compared to the control group at 12, 18, and 24months, which were 84%, 80%, and 80% vs. 55%, 35%, and 20%, respectively (P<0.02). There was a significant reduction in the anastomotic neointimal area and neointimal cell proliferation in Propaten grafts compared with control grafts at all groups between 6 and 24months (P<0.05). Heparin bioactivity as measured by antithrombin binding assay was demonstrated in the Propaten graft between 1 and 24months. Mean heparin activities on Propaten grafts ranged from 26.3±6.4 pmol/cm2 to 18.4±8.7 pmol/cm2 between 1 and 24months, which were significantly greater than the control group (P<0.001). Differences between mean heparin activities of explanted Propaten graft samples at the various time points were nonsignificant (P>0.05). Heparin-bonded ePTFE graft provides a thromboresistant surface and reduced anastomotic intimal hyperplasia at 2 years. The stable heparin bioactivity of the Propaten graft confers an advantage in long-term graft patency.

Transmural capillary ingrowth is essential for confluent vascular graft healing.

In addition to the full elucidation of, and differentiation between, the three healing/endothelialisation modes of vascular grafts, the significance of the work relates to the near-complete lack of endothelialisation of small diameter vascular grafts in humans (1-2 cm transanastomotic outgrowth on a graft that may be 60 cm long) even after decades of implantation. The concomitant retained midgraft thrombogenicity leads, together with anastomotic hyperplastic responses, to poor long-term outcomes. The large impact of successful translation of the current research to the achievement of full endothelialisation of long peripheral grafts in humans via transmural ingrowth (half a millimetre distance; thickness of the graft wall), is evident, and supported by the large improvements in clinical patencies achievable in by pre-seeding of ePTFE grafts with confluent endothelia.

Susceptibility of ePTFE vascular grafts and bioengineered human acellular vessels to infection

BackgroundSynthetic expanded polytetrafluorethylene (ePTFE) grafts are routinely used for vascular repair and reconstruction but prone to sustained bacterial infections. Investigational bioengineered human acellular vessels (HAVs) have shown clinical success and may confer lower susceptibility to infection. Here we directly compared the susceptibility of ePTFE grafts and HAV to bacterial contamination in a preclinical model of infection. Materials and methodsSections (1 cm2) of ePTFE (n = 42) or HAV (n = 42) were inserted within bilateral subcutaneous pockets on the dorsum of rats and inoculated with Staphylococcus aureus (107 CFU/0.25 mL) or Escherichia coli (108 CFU/0.25 mL) before wound closure. Two weeks later, the implant sites were scored for abscess formation and explanted materials were halved for quantification of microbial recovery and histological analyses. ResultsThe ePTFE implants had significantly higher abscess formation scores for both S. aureus and E. coli inoculations compared to that of HAV. In addition, significantly more bacteria were recovered from explanted ePTFE compared to HAV. Gram staining of explanted tissue sections revealed interstitial bacterial contamination within ePTFE, whereas no bacteria were identified in HAV tissue sections. Numerous CD45+ leukocytes, predominantly neutrophils, were found surrounding the ePTFE implants but minimal intact neutrophils were observed within the ePTFE matrix. The host cells surrounding and infiltrating the HAV explants were primarily nonleukocytes (CD45−). ConclusionsIn an established animal model of infection, HAV was significantly less susceptible to bacterial colonization and abscess formation than ePTFE. The preclinical findings presented in this manuscript, combined with previously published clinical observations, suggest that bioengineered HAV may exhibit low rates of infection.

Development of expanded polytetrafluoroethylene cardiovascular graft platform based on immobilization of poly lactic-co-glycolic acid nanoparticles using a wet chemical modification technique

Expanded polytetrafluoroethylene ePTFE grafts are mostly employed to replace damaged blood vessels and to restore normal blood flow. However, the dilemma of early thrombosis, inflammation, and development of biofilms after implantation limit ePTFE long-term patency and restrict the patient’s life quality. In this study, poly lactic-co-glycolic acid (PLGA) nanoparticles were covalently immobilized on ePTFE surface for local therapeutic purposes. First, the ePTFE surface was primarily oxidized by H2O2/H2SO4 solution to create hydroxyl groups. Consequently, free amino groups were introduced onto ePTFE surface by an aminolyzation reaction of the activated hydroxyl groups using 3-aminopropyl triethoxysilane. The produced amino groups were further used as anchor sites for covalent immobilization of previously prepared PLGA nanoparticles. The functional groups originated on ePTFE surface were confirmed by FTIR analysis. Furthermore, the scanning electron microscopy visualization evidenced a homogeneous distribution pattern of the immobilized PLGA nanoparticles on the surface. The immobilized PLGA nanoparticles showed stability on ePTFE surface under blood flow mimetic conditions. Additionally, light microscopy observation confirmed the biocompatibility of mouse L929 fibroblasts on the nano-coated ePTFE graft. The cellular adhesion and growth did not reveal remarkable cytotoxicity in the tested modified ePTFE grafts.

Assessing the Safety of Expanded Polytetrafluoroethylene Synthetic Grafts in Living Donor Liver Transplantation: Graft Migration Into Hollow Viscous Organs - Diagnosis and Treatment Options.

BackgroundOur recent studies have highlighted the importance and safety of backtable venoplasty for middle hepatic vein (MHV) and inferior right hepatic veins (IRHV) reconstruction using expanded polytetrafluoroethylene (ePTFE) vascular grafts. In this study, we aim to analyze the complications associated with ePTFE graft use and discuss the management of the rare, but, potentially life threatening complications directly related to ePTFE conduits.Material/MethodsFrom January 2012 to October 2015 a total of 397 patients underwent living donor liver transplantation (LDLT). The ePTFE vascular grafts were used during the backtable venoplasty for outflow reconstruction in 262 of the liver allografts. Recipients who developed ePTFE-related complications were analyzed.ResultsePTFE-related complications developed in 1.52% (4/262) of the patients. One patient (0.38%) developed complete thrombosis with sepsis at 24 months post-transplantation and died due to multiorgan failure. Three patients (1.1%) developed graft migration into the second portion of the duodenum, without overt peritonitis. Surgical exploration and ePTFE graft removal was done in all the patients. One patient died due to overwhelming sepsis.ConclusionsePTFE graft migration into the duodenum causing perforation is a new set of complications that has been recently described in LDLT and can be treated effectively by surgical removal of the infected vascular graft and duodenal perforation closure. Despite of such complications, in our experience, ePTFE use in LDLT continues to have wide safety margin, with a complication rate of only 1.52%.

In vitro and in vivo evaluation of a small-caliber coaxial electrospun vascular graft loaded with heparin and VEGF

IntroductionTo date, clinically available expanded polytetrafluoro-ethylene (ePTFE) vascular grafts are suboptimal for reconstructing small caliber (D < 6 mm) arteries, owing to thrombosis in early and restenosis in late stage. Our aim in this preliminary study was to fabricate a nano-fibrous vascular graft which was biofunctionalized with VEGF165 and heparin. The short term performance was evaluated both in vitro and in vivo. MethodFour-mm caliber grafts were prepared by the coaxial-elctrospun technique, which consisted of poly(l-lactide-co-caprolactone) [P(LLA-CL)] collagen and elastin. Heparin and endothelial cell growth factor-165 (VEGF165) were encapsulated in the core of the fibrous. Controlled release of the heparin and VEGF165 were evaluated for 28 days. Endothelial cells were cultured on the electrospun grafts or ePTFE grafts as controls. The cellular adhesion, proliferation and morphology were examined. Electrospun or ePTFE grafts were randomly implanted into a rabbit infrarenal aortic replacement model (n = 30) for 28 days without any antiplatelet therapy. At the termination, all grafts were examined by Doppler ultrasound and then evaluated with histology and scanning electron microscopy. ResultsThe cumulative release amount of heparin (6.93 ± 1.03 mg) and VEGF165 (22.17 ± 5.56 μg) during 28 days were measured. Endothelial cells cultured on electrospun grafts showed significantly higher attachment efficiency and proliferation compared to the ePTFE ones (P < 0.001). At 2 h more ECs had attached to the P(LLA-CL)/Collagen/Elatin grafts (83.26 ± 8.02%) compared to P(LLA-CL) (67.07 ± 4.16%) and ePTFE (46.87 ± 8.85%). ECs proliferated faster on VEGF loaded grafts (O.D = 2.9 ± 1.2, n = 12) compared to ePTFE (O.D = 1.7 ± 1.0, n = 12). The patency was significantly higher in electrospun grafts (86.6%) than ePTFE grafts (40.0%) (P = 0.021). Correspondingly, the microscope images of electrospun implants showed little thrombus when compared with the ePTFE implants. ConclusionBiofunctionalized electrospun graft showed surgical properties, hemocompatibility and higher short-term patency compared with the ePTFE grafts. Despite good early performances, profound study should be designed for long-term evaluation.

IP229 Proposal of a Multicentric-Based Score for Graft Patency in Below-knee Femoropopliteal Bypass With Heparin-Bonded ePTFE Graft in Patients With Critical Limb Ischemia

IP229 Proposal of a Multicentric-Based Score for Graft Patency in Below-knee Femoropopliteal Bypass With Heparin-Bonded ePTFE Graft in Patients With Critical Limb Ischemia

Domino Reconstruction of the Portal Vein Using the External Iliac Vein and an ePTFE Graft in Pancreatic Surgery

BackgroundIn the portal vein resection of long distance, an interposition by autologous vein is mandatory. External iliac vein (EIV) has been used, but harvesting the EIV is associated with severe venous congestion of the affected lower extremity. We have reconstructed the EIV using a ringed expanded polytetrafluoroethylene (ePTFE) graft. MethodsThirteen patients underwent this surgery. The right EIV was used for reconstructing the portal vein, and the retrieved portion of EIV was interposed by the ePTFE graft. We evaluated size and length of the graft, graft patency, girth of thigh, time for reconstruction of EIV, and graft infection. ResultsePTFE grafts of 8 or 10 mm in diameter were used. The length of ePTFE graft used was 4.4±0.5 cm. Graft patency was kept in 76.9% patients. Graft obstruction was encountered in three patients, and the girth of right thigh increased by about 10 cm. Time for reconstruction of EIV was 29.5±6.8 min. Graft infection did not occur in any patients. ConclusionsReconstruction of the EIV using a ringed ePTFE graft seems to be a feasible option for preventing the swelling of the affected lower extremity after procurement of EIV for repairing the portal vein.

Long term performance evaluation of small-diameter vascular grafts based on polyvinyl alcohol hydrogel and dextran and MSCs-based therapies using the ovine pre-clinical animal model

The functional and structural performance of a 5cm synthetic small diameter vascular graft (SDVG) produced by the copolymerization of polyvinyl alcohol hydrogel with low molecular weight dextran (PVA/Dx graft) associated to mesenchymal stem cells (MSCs)-based therapies and anticoagulant treatment with heparin, clopidogrel and warfarin was tested using the ovine model during the healing period of 24 weeks. The results were compared to the ones obtained with standard expanded polyetetrafluoroethylene grafts (ePTFE graft). Blood flow, vessel and graft diameter measurements, graft appearance and patency rate (PR), thrombus, stenosis and collateral vessel formation were evaluated by B-mode ultrasound, audio and color flow Doppler. Graft and regenerated vessels morphologic evaluation was performed by scanning electronic microscopy (SEM), histopathological and immunohistochemical analysis. All PVA/Dx grafts could maintain a similar or higher PR and systolic/diastolic laminar blood flow velocities were similar to ePTFE grafts. CD14 (macrophages) and α-actin (smooth muscle) staining presented similar results in PVA/Dx/MSCs and ePTFE graft groups. Fibrosis layer was lower and endothelial cells were only detected at graft-artery transitions where it was added the MSCs. In conclusion, PVA/Dx graft can be an excellent scaffold candidate for vascular reconstruction, including clinic mechanically challenging applications, such as SDVGs, especially when associated to MSCs-based therapies to promote higher endothelialization and lower fibrosis of the vascular prosthesis, but also higher PR values.

Surface Coating of Polytetrafluoroethylene with Extracellular Matrix and Anti-CD34 Antibodies Facilitates Endothelialization and Inhibits Platelet Adhesion Under Sheer Stress.

Expanded polytetrafluoroethylene (ePTFE) polymers do not support endothelialization because of nonconductive characteristics towards cellular attachment. Inner surface modification of the grafts can improve endothelialization and increase the long-term patency rate of the ePTFE vascular grafts. Here we reported a method of inner-surface modification of ePTFE vascular graft with extracellular matrix (ECM) and CD34 monoclonal antibodies (CD34 mAb) to stimulate the adhesion and proliferation of circulating endothelial progenitor cells on ePTFE graft to enhance graft endothelialization. The inner surface of ECM-coated ePTFE grafts were linked with CD34 mAb in the presence of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide/N-hydroxysuccinimide (EDC/NHS) solution and the physicochemical properties, surface morphology, biocompatibility, and hemocompatibility of the grafts were studied. The hydrophilicity of CD34 mAb-coated graft inner surface was significantly improved. Fourier transform infrared spectroscopy analysis confirmed ECM and CD34 mAb cross-linking in the ePTFE vascular grafts with our method. Scanning electron microscopy analysis showed protein layer covering uniformly on the inner surface of the modified grafts. The cell-counting kit-8 (CCK-8) assay confirmed that the modified graft has no obvious cytotoxicity. The modified graft showed a low hemolytic rate (0.9%) in the direct contact hemolysis test, suggesting the modification improved hemocompatibility of biopolymers. The modification also decreased adhesion of platelets, while significantly increased the adhesion of endothelial cells on the grafts. We conclude that our method enables ePTFE polymers modification with ECM and CD34 mAb, facilitates endothelialization, and inhibits platelet adhesion on the grafts, thus may increase the long-term patency rate of the prosthetic bypass grafts.

Early cannulation graft Flixene™ for conventional and complex hemodialysis access creation.

The Flixene™ (Atrium™, Hudson, NH) is a trilaminate composite polytetrafluoroethylene (PTFE) graft that allows access within 72 hours. We evaluate our initial experience with this device for conventional and complex hemodialysis access creation. Retrospective review in end-stage renal disease (ESRD) patients who underwent access creation with Flixene from January 2013 to July 2014. For our analysis, the patients were divided in two groups: those with complex access configurations tunneled in the chest and/or abdominal wall (thoraco-abdominal wall access [TAWA]), and those tunneled in conventional sites (extremity access [EA]). Patient's demographics, indications, complications, reinterventions, patency rates and factors influencing outcomes were evaluated. In 19 patients (54% men; mean age 44 years ± 18), 24 grafts were implanted, (13 EA [54%] vs. 11 TAWA), all patent after surgery. Central venous occlusive disease (CVOD) was present in all patients with TAWA and in 7/13 (54%) EA patients (p = 0.016). Early cannulation (within 72 hours) was successful in 12 EA and 5 TAWA grafts (p = 0.044). Complication rates including infection, thrombosis, bleeding and steal syndrome were 8/11 (73%) in TAWA and 5/13 (38%) in EA (p = 0.02). At 12 months, primary patency rates for EA and TAWA were 25% and 41%; secondary patency rates were 55% and 41%, respectively. Early cannulation (EC) grafts are viable alternatives for conventional and complex access creation that allowed early cannulation (<72 hours) in 17 (70%) of our cases. Primary and secondary patency rates at 12 months were equivalent to data reported on ePTFE grafts.

Drug eluting grafts for hemodialysis access.

The development of new methods for drug elution of graft material, biofiber films and resurfacing of prosthetic graft surfaces offers new opportunities for improvement of graft function in arteriovenous (AV) access. Three areas of research include developing grafts that reduce the development of neointimal hyperplasia, reducing infection and reducing thrombogenicity. The only drug eluting graft presently being used, is the heparin coated expanded polytetrafluoroethylene (ePTFE) graft, which has been shown to decrease the incidence of early thrombosis. New drug eluting grafts include those with paclitaxel and those with antibiotics. The development of a hybrid coated prosthetic graft that can deliver targeted gene therapies holds great promise in the field.

Bovine carotid artery biologic graft outperforms expanded polytetrafluoroethylene for hemodialysis access

ObjectiveArteriovenous grafts remain reliable substitutes for permanent hemodialysis access in patients without a suitable autogenous conduit. Advances in conduit design and endovascular management of access-related complications question the preference for synthetic conduits over biologic grafts in contemporary practice. In this study, we compared outcomes between a bovine carotid artery (BCA) biologic graft and expanded polytetrafluoroethylene (ePTFE) grafts for hemodialysis access in a recent cohort of patients. MethodsThis was a single-institution retrospective review of 120 consecutive grafts placed in 98 patients between January 1, 2011, and June 30, 2014. Univariate methods (χ2, analysis of variance, t-test) were used to compare demographic and medical characteristics of patients who received each graft type. Kaplan-Meier, log-rank tests, univariate and multivariate logistic analyses, and Cox regression analyses were used to evaluate patency and graft complications. Outcomes were defined and analyzed according to reporting guidelines published by the Society for Vascular Surgery. ResultsOf the 120 grafts studied, 52 (43%) were BCA and 68 (57%) were ePTFE. Successful graft use for dialysis was 96% (95% confidence interval [CI], 90%-100%) for BCA and 84% (95% CI, 74%-93%) for ePTFE (P = .055). Comparing BCA vs ePTFE, estimates for primary patency were 30% vs 43% at 1 year and 16% vs 29% at 2 years (P = .27). Primary assisted patency was 36% vs 45% at 1 year and 24% vs 35% at 2 years (P = .57). Secondary patency was 67% vs 48% at 1 year and 67% vs 38% at 2 years (P = .05). There were no differences in primary (hazard ratio [HR], 0.70; 95% CI, 0.40-1.28; P = .25) and primary assisted (HR, 0.87; 95% CI, 0.46-1.65; P = .67) patency for BCA compared with ePTFE. However, secondary patency was higher for BCA compared with ePTFE (HR, 2.92; 95% CI, 1.29-6.61; P = .01). Graft infection rates during the study period were 15.4% for BCA and 20.6% for ePTFE (P = .47). The significant predictors of graft failure were higher body mass index (HR, 1.06; 95% CI, 1.00-1.11; P = .04) and hyperlipidemia (HR, 2.94; 95% CI, 1.27-6.76; P = .01). ConclusionsIn this study of a recent cohort of patients who received arteriovenous grafts, primary and primary assisted patencies were similar between BCA and ePTFE grafts. However, secondary patency was higher for BCA, indicating better durability for the biologic graft than for ePTFE grafts in patients whose anatomy preclude placement of an arteriovenous fistula.