ePTFE Grafts Research Articles

Polytetrafluoroethylene and Bovine Mesenterial Vein Grafts for Hemodialysis Access: A Comparative Study

Purpose This study aimed to evaluate the safety and patency rate of bovine mesenterial vein grafts (BMVG) for vascular access (VA) in hemodialysis patients (HDP), compared to expanded polytetrafluorethylene (ePTFE grafts) over a mid- to long-term period. Methods Patency and complication rate of 23 consecutive HDP with BMVG for VA were compared to a control group consisting of 23 similar HDP with ePTFE grafts. In both groups, the graft was placed preferably in a forearm loop configuration. The same surgeon performed all procedures. All patients were followed over a period of 4 yrs. Results Graft placement was successful in all patients. Patency rates did not differ significantly in both groups. However, there were less severe complications in the BMVG group. Conclusion The BMVG is a viable alternative for HD access in patients where autologous construction is not possible, and should be given priority in patients with a failed ePTFE graft or high risk for infection.

Randomized comparison of percutaneous Viabahn stent grafts vs prosthetic femoral-popliteal bypass in the treatment of superficial femoral arterial occlusive disease

This randomized prospective study was designed to compare the effectiveness of treating superficial femoral artery occlusive disease percutaneously with expanded polytetrafluoroethylene (ePTFE)/nitinol self-expanding stent grafts vs surgical femoral-to-above knee (AK) popliteal artery bypass with synthetic graft material. From March 2004 to May 2005, 100 limbs in 86 patients with femoral-popliteal arterial occlusive disease were identified. Patients had symptoms ranging from claudication to rest pain, with or without tissue loss, and were prospectively randomized for treatment into one of two groups. The limbs were treated percutaneously with angioplasty and one or more self-expanding stent grafts (n = 50) or surgically with femoral-to-AK popliteal artery bypass using synthetic Dacron or ePTFE grafts (n = 50). The mean +/- SD total length of artery stented was 25.6 +/- 15 cm. Follow-up evaluation with ankle-brachial indices and color flow duplex sonography imaging were performed at 3, 6, 9, and 12 months after treatment. Patients were monitored for a median of 18 months. No statistical difference was found in the primary patency (P = .895) or secondary patency (P = .861) between the two treatment groups. Primary patency at 3, 6, 9, and 12 months of follow-up was 84%, 82%, 75.6%, and 73.5% for the stent graft group and 90%, 81.8%, 79.7%, and 74.2% for the femoral-popliteal surgical group. Thirteen patients in the stent graft group had 14 reinterventions, and 12 reinterventions occurred in the surgical group. This resulted in secondary patency rates of 83.9% for the stent graft group and 83.7% for the surgical group at the 12-month follow-up. Management of femoral-popliteal arterial occlusive disease using percutaneous treatment with a stent graft is comparable with surgical revascularization with conventional femoral-to-AK popliteal artery bypass using synthetic material up to 12 months. Longer-term follow-up would be helpful in determining ongoing efficacy.

Impact of Cuffed, Expanded Polytetrafluoroethylene Dialysis Grafts on Graft Outlet Stenosis

The objective of this study was to determine prospectively the difference between the graft outlet strictures of a polytetrafluoroethylene (ePTFE) graft with a cuff at the graft-vein anastomosis (Venaflo; Bard industries, Tempe, Ariz.) and that of the regular ePTFE graft (Stretch Gore-Tex; Gore, Flagstaff, Ariz.) placed for hemodialysis access. Between January and April 2005, 36 consecutive patients (average age: 63.3 years) underwent ePTFE graft implantation (36 implantations) for hemodialysis at the Vascular Surgery Section of Chang Gung Memorial Hospital. The patients of the study cohort were randomly assigned to two groups based on the graft used: cuffed graft group (Venaflo graft) and non-cuffed standard graft group (Gore-Tex graft). Each patient underwent antegrade venography at the 3-month follow-up to demonstrate the graft outlet stricture. Results of the graft outlet angiography analysis were examined, and all medical records were reviewed at end of the study. The degree of the graft outlet stenosis was compared between the two groups. Average stenosis of the cuffed graft group and non-cuffed (standard) graft group were 22.76 +/- 26.37%% and 44.95 +/- 27.48%%, respectively; the difference between the two groups was statistically significant (P < 0.05). The graft outlet stricture of cuffed ePTFE grafts for hemodialysis 3 months after implantation was less severe than that for the standard ePTFE graft. The correlation between the stricture level and dialysis graft patency requires further clarification.

The effect of a recombinant elastin-mimetic coating of an ePTFE prosthesis on acute thrombogenicity in a baboon arteriovenous shunt

A recombinant elastin-mimetic triblock protein polymer with an inverse transition temperature (∼20 °C) was used to impregnate small-diameter (4 mm i.d.) expanded polytetrafluoroethylene (ePTFE) vascular grafts. Scanning electron microscopy confirmed that initial elastin impregnation of the graft followed by further multilayer coating with elastin films filled in the fibril and node structure of the luminal surface of the ePTFE graft and was macroscopically smooth. Elastin protein polymer impregnation reduced the advancing contact angle of the luminal surface to 43°, which was comparable to the advancing contact angle of 47° for a cast elastin film. Attenuated total reflection infrared spectroscopy and Coomassie blue staining revealed little discernable change in the protein surface film after 24 h of shear at 500 s −1 and 37 °C. Excellent short-term blood-contacting properties as determined by minimal fibrin and platelet deposition were demonstrated using a baboon extracorporeal femoral arteriovenous shunt model. The results of this study demonstrate the applicability of an elastin-mimetic triblock protein polymer as a non-thrombogenic coating or as a component of a tissue-engineered composite.

Expanded polytetrafluoroethylene graft for bypass surgery using the excimer laser–assisted nonocclusive anastomosis technique

Patients with complex craniocerebral pathophysiologies such as giant cerebral aneurysms, skull base tumors, and/or carotid artery occlusive disease are candidates for a revascularization procedure to augment or preserve cerebral blood flow. However, the brain is susceptible to ischemia, and therefore the excimer laser-assisted nonocclusive anastomosis (ELANA) technique has been developed to overcome temporary occlusion. Harvesting autologous vessels of reasonable quality, which is necessary for this technique, may at times be problematic or impossible due to the underlying systemic vascular disease. The use of artificial vessels is therefore an alternative graft for revascularization. Note, however, that it is unknown to what degree these grafts are subject to occlusion using the ELANA anastomosis technique. Therefore, the authors studied the ELANA technique in combination with an expanded polytetrafluoroethylene (ePTFE) graft. The experimental surgeries involved bypassing the abdominal aorta in the rabbit. Ten rabbits were subjected to operations representing 20 ePTFE graft-ELANA end-to-side anastomoses. Intraoperative blood flow, followup angiograms, and long-term histological characteristics were assessed 75, 125, and 180 days postoperatively. Angiography results proved long-term patency of ePTFE grafts in all animals at all time points studied. Data from the histological analysis showed minimal intimal reaction at the anastomosis site up to 180 days postoperatively. Endothelialization of the ePTFE graft was progressive over time. The ELANA technique in combination with the ePTFE graft seems to have favorable attributes for end-to-side anastomoses and may be suitable for bypass procedures.

TIMP-2 Modulates Neointimal Formation in Experimental ePTFE Arterial Grafts

In vascular reconstructive surgery, myointimal hyperplasia contributes to the adverse outcome of synthetic grafts. This phenomenon is because of unregulated extracellular matrix degradation and remodeling, and excessive smooth muscle cell proliferation and migration. Matrix metallopreoteinase 2 (MMP-2) is known as an important contributor to these events. The aims of our study was to investigate the effects of selective MMP-2 inhibitor (TIMP-2) in endothelialization rate, SMC proliferation, and myointimal hyperplasia in experimental ePTFE arterial grafts. In 20 male Lewis rats, a 1-cm long ePTFE graft has been inserted at the level of the abdominal aorta. Animals were randomized in two groups (10 animals each): group A received six subcutaneous inoculations of TIMP-2 (2.5 microg) after surgery, group B received only the vehicle of TIMP-2. Neointimal thickness, as well as SMC density, were augmented in group B, whereas endothelial cells density was augmented in group A, and these findings were statistically significant. In group A SMC were better organized, just like SMC of thoracic aorta. In group B SMC were no organized. Furthermore, anti-TIMP-2 and anti-MMP-2 coloration revealed higher levels of TIMP-2 and lower levels of MMP-2 in group A versus group-B. Use of TIMP-2 affects the neointimal formation of experimental e-PTFE arterial grafts, leading to a better-organized neointima, with improved endothelialization.

Improved Neo-Endothelialization of Small Diameter ePTFE Grafts with Titanium Coating

Patency of small synthetic bypass grafts is inferior compared to autologous grafts for revascularization procedures. Titanium coating of foreign surfaces has shown to decrease thrombogenicity, enhance biocompatibility and promote adhesion of endothelial cells. The aim of this study was to test the effect of titanium coating of small diameter ePTFE grafts on short term patency, neo-endothelialization and neointimal proliferation. Bilateral carotid graft interposition was performed in 5 pigs with uncoated (n=5) and titanium-coated (n=5) ePTFE grafts (internal diameter=4 mm, length=5 cm), thus each pig served as its own control. At the end of the study (30 +/- 3 days), patency and stenosis severity was assessed by carotid angiography. Animals were sacrificed and grafts were excised for histology and scanning electron microscopy. Morphometry of histologic sections was carried out to determine neointimal proliferation and percentage of neo-endothelial coverage. Patency rate was 80% for uncoated and titanium-coated grafts. Quantitative angiography did not show any significant difference in lumen size between two groups. Morphometry revealed a significantly higher cellular coverage with CD31 positive endothelial cells for titanium-coated (84 +/- 19%) than uncoated grafts (48 +/- 26%, p<0.001). There was a non significant trend (p=0.112) towards increased neointimal proliferation in titanium-coated (94 +/- 61 micron2/micron) compared to uncoated grafts (60 +/- 57 micron2/micron). Patency rate in uncoated and titanium-coated ePTFE grafts is similar at one month. However, titanium coated grafts show a significant improvement in neo-endothelialization compared to uncoated grafts.

Diffusion of bioactive molecules through the walls of the medial tissue‐engineered hybrid ePTFE grafts for applications in designs of vascular tissue regeneration

Strategies of better vascular tissue engineering may require delivery of soluble bioactive signals in cell culture medium to the cells in tissue-regenerating constructs. We measured the diffusivity and permeability of model tissue-engineering bioactive molecules such as water and heparin through the walls of both a hybrid ePTFE graft and a porcine carotid artery, a model vascular tissue. While diffusivities of H(3)-water and H(3)-heparin were measured as 3.9 x 10(-) (6) and 1.6 x 10(-) (6) cm(2)/s in the artery, respectively, under diffusional circulation of cell culture medium through the lumens of the carotid arteries, their corresponding permeabilities were 4.7 x 10(-) (5) and 2.0 x 10(-) (5) cm/s. On the other hand, diffusivities of H(3)-water and H(3)-heparin were also measured as 5.1 x 10(-) (6) and 4.7 x 10(-) (6) cm(2)/s, respectively, in the tissue-engineered hybrid ePTFE grafts; their corresponding permeabilities were 5.1 x 10(-) (5) and 3.7 x 10(-) (5) cm/s. The hybrid graft tissues were engineered by replacing the biodegradable, porous poly(lactide-co-glycolide) layers coated on the ePTFE surfaces with smooth muscle cell-derived tissues for 6 weeks. We analyzed the morphologies of the artery and the engineered hybrid ePTFE tissues with scanning electron microscopy and H&E stains. While the artery had its typical structure properties with layers of intima, media and adventitia, the tissue-engineered ePTFE hybrid graft had two layers of engineered tissues on the inner and outer surfaces of the ePTFE. There were no significant differences among the luminal tissue morphologies of the test samples from the effects of diffusion flow applications, with minor changes on their luminal surfaces. The results of water and heparin diffusion experiments indicated that these bioactive molecules were well transported from the cell culture medium to the tissue-engineering cells, enough to support tissue regeneration. We hope that these transport results may elucidate the transport behaviors of soluble nutrient molecules and biological signals through the vascular constructs under tissue engineering processes.

The Use of Covered Nitinol Stents to Salvage Dialysis Grafts After Multiple Failures

The increasing number of patients requiring hemodialysis and the limited number of access sites have resulted in an increase in multiple graft revisions to maintain access for hemodialysis. Venous outflow or anastomotic stenoses in vascular grafts tend to recur and contribute to the difficulty in maintaining a functioning graft. Thus, extending the life of a failed graft becomes an important objective of this study, which was to assess the use of covered nitinol stents to salvage expanded polytetrafluoroethylene (ePTFE) grafts with venous anastomotic or outflow stenosis that have failed after multiple revisions. This is a review of 8 failed non-autogenous ePTFE grafts with isolated venous anastomotic or proximal outflow stenoses that had undergone multiple previous revisions, had failed percutaneous transluminal angioplasty (PTA), and required placement of a covered nitinol stent. Graft locations were forearm (2), upper arm (4), and femoral (2). The mean number of interventions per patient before stent placement was 5.87 thrombectomies (range 2-28) and 3.38 balloon angioplasties (range 2-19). Five patients had 0.62 interposition grafting and 3 had patch angioplasty. All 8 patients (100%) underwent successful dialysis after thrombectomy and stenting. The primary and secondary patency rates after stent placement were 50% and 75%, and 25% and 75%, at 3 and 6 months, respectively. Percutaneous thrombectomy, balloon angioplasty, and concomitant covered nitinol stent placement extend the function of hemodialysis access grafts that have previously failed multiple times.

Functional properties of fresh and cryopreserved carotid and femoral arteries, and of venous and synthetic grafts: comparison with arteries from normotensive and hypertensive patients

The ideal arterial graft must share identical functional properties with the host artery. Surgical reconstruction of the common carotid artery (CA) is performed in several clinical situations, using expanded polytetrafluoroethylene prosthesis (ePTFE) or saphenous vein (SV) grafts. At date there is interest in obtaining an arterial graft that improves the results of that nowadays available. The use of a fresh or cryopreserved/defrosted artery appears as an interesting alternative. However, if the fresh and cryopreserved/defrosted arteries allow an adequate viscoelastic and functional matching with the host arteries needs to be established. The aims were to compare the viscoelastic and functional performance of: (1) conduits used in CA reconstruction (SV and ePTFE) with those of the fresh and cryopreserved/ defrosted CA and femoral arteries (FA), and (2) normotensive and hypertensive patients' arteries with those of the arterial substitutes in vitro analyzed. Pressure, diameter and wall thickness of the CA were recorded in 15 normotensive and 15 hypertensive patients (in vivo studies), and in SV, fresh and cryopreserved/defrosted CA and FA (obtained from 15 donors), and ePTFE segments (in vitro studies). From stress-strain relationship we calculated elastic and viscous modulus, and the characteristic impedance. The local buffer and conduit functions were quantified as the viscous/elastic quotient and the inverse of the characteristic impedance. Fresh and cryopreserved/defrosted CA and FA were more alike, both in viscoelastic and functional levels, respect to normotensive and hypertensive patients' arteries, than the ePTFE and SV grafts. CA and FA cryografts could be considered an important alternative for carotid reconstruction.

Modulating Expanded Polytetrafluoroethylene Vascular Graft Host Response via Citric Acid‐Based Biodegradable Elastomers

A biodegradable polyester elastomer, poly(1,8-octanediol citrate) (POC), is used to modify the lumen of expanded polytetrafluoroethylene (ePTFE) grafts via a spin-shearing method followed by interfacial in situ polycondensation. We demonstrate successful surface modification of ePTFE grafts without affecting graft compliance (see figure). The POC interface confers hydrophilicity, reduced thrombogenicity, facilitated graft endothelialization in vitro, and reduced macrophage infiltration on the ePTFE grafts.

PEG-hirudin/iloprost Coating of Small Diameter ePTFE Grafts Effectively Prevents Pseudointima and Intimal Hyperplasia Development

Small diameter PTFE grafts are prone to thrombosis and intimal hyperplasia development. Heparin graft coating has beneficial effects but also potential drawbacks. The purpose of this study was to evaluate the experimental efficacy of PEG-hirudin/iloprost coated small caliber PTFE grafts. Thirty-six femoro-popliteal ePTFE grafts (expanded polytetrafluoroethylene, diameter 4 mm) were inserted into 18 pigs. Grafts were randomised individually for each leg and grouped for 3 groups. Group I consisted of native ePTFE grafts, group II were grafts coated with a polylactide polymer (PLA) without drugs and group III grafts were coated with PLA containing a polyethylene glycol (PEG)-hirudin/iloprost combination. The follow-up period was 6 weeks. Patency rates were calculated and development of pseudointima inside the grafts was noted. Thickness of intimal hyperplasia at the distal anastomoses was measured using light microscopy. Patency rates for group I were 6/9 (67%), for group II 9/10 (90%) and 12/12 (100%) for group III. In groups I and II there was a significant reduction of blood flow proximal to the graft at graft harvest, to 29+/-12 and 28+/-20 ml/min respectively (both p<0.01 versus preoperative value), whilst in group III blood flow, 99+/-21 ml/min, remained at the preoperative level. Subtotal stenosis due to development of pseudointima was noted in each of the native and PLA coated grafts but not in group III grafts. Intimal hyperplasia at the distal anastomosis was lowest in group III. The PEG-hirudin/iloprost coating of ePTFE prostheses effectively reduced pseudointima and intimal hyperplasia development and led to superior graft patency.

Bovine ureter graft for haemodialysis access surgery**This article was presented as an oral presentation in the 54th International Congress of the European Society for Cardiovascular Surgery, Athens, Greece, May 19–22, Interactive Cardiovascular and Thoracic Surgery, Vol. 4 (Suppl 1), May 2005.

Bovine ureter SynerGraft (SG) (CryoLife, Inc.) has been recently introduced into haemodialysis access surgery. It is a non-glutaraldehyde fixed acellular collagen and elastin matrix conduit that may withstand arterial pressures. There has only been one published report in humans with this graft for vascular access, except for a canine model which Matsuura et al. reported [1]. In this study, we report the early and mid-term outcome of bovine ureter as a haemodialysis access graft in chronic haemodialysis. Four female patients with an average age of 44.5 years (range 25–67 years) underwent surgery in November 2004, using the bovine ureter SynerGraft (CryoLife, Inc.) as a conduit for haemodialysis access surgery. The operations were indicated in these patients, as they had no suitable superficial venous system to create an arteriovenous fistula; they also had previously failed arteriovenous fistulas and expanded polytetra flouroethylene (ePTFE) grafts in several different locations. The patients were evaluated with Doppler ultrasound which revealed normal deep venous system. All the patients were informed about the graft and written consents were taken prior to the operation. The operations were done under axillary block. The xenografts were implanted between the brachial artery and the axillary vein in two patients, and between the radial artery and the deep brachial vein in two patients. After systemic heparinization, the graft was anastomosed to the artery in an end-to-side fashion, using a running 6/0 polypropylene suture. The artery was declamped to fill the graft. The graft was passed through the tunnel and the venous anastomosis was done using the same suturing technique. Heparin was not neutralized after the anastomosis. All grafts were allowed for a 6-week maturation for the remodelling of the vascular prosthesis prior to haemodialysis. The grafts were accessed three times a week for haemodialysis. All grafts implanted were patent on the first postoperative day. One of the grafts between the brachial artery and the axillary vein failed at the end of the second month after four times of haemodialysis. A severe aneurysm and pseudoaneurysm formation occurred in the other graft after a fifth intervention for haemodialysis. This required total excision of the graft and saphenous vein interpositioning to the brachial artery. At the end of the third month, both of the grafts between the radial artery and the brachial vein were patent and the patients had had several haemodialysis sessions. However, these grafts also failed at the end of fifth and sixth months. A recently occluded graft was re-operated for thrombectomy, but it re-occluded in the first post-operative day. The patency rates of the grafts by means of graft location are seen in Table 1.

True Aneurysm of Extracranial Internal Carotid Artery in a 10-year-old

In this report, we describe a very unusual case, true aneurysm of the internal carotid artery, in a child. A 10-year-old boy with a pulsating mass on his right neck was admitted with the diagnosis of a 25 mm by 50 mm true aneurysm of the right internal carotid artery, which was resected, and a 5-mm ePTFE graft was interposed. He was discharged on day 3 without complications. Prompt differential diagnosis of this pathology is crucially important. Open surgery yields acceptable results depending on the size, extension and the type of the aneurysm.

Paclitaxel-coated expanded polytetrafluoroethylene haemodialysis grafts inhibit neointimal hyperplasia in porcine model of graft stenosis

The main pathology of haemodialysis graft stenosis is venous neointimal hyperplasia at graft-venous anastomoses. Neointimal hyperplasia is also observed in cases of coronary artery in-stent restenosis. Paclitaxel is a chemotherapeutic agent used to treat cancer, and has been proven to inhibit neointimal hyperplasia of coronary artery in-stent restenosis. In this study, we examined whether a paclitaxel-coated haemodialysis graft could inhibit neointimal hyperplasia and prevent stenosis. We dip-coated paclitaxel on expanded polytetrafluoroethylene (ePTFE) grafts at a dose density of 0.59 microg/mm(2). In vitro release tests showed an initial paclitaxel burst followed by a long-term slow release. Using ePTFE grafts with (coated group, n = 8) or without a paclitaxel coating (control group, n = 11), we constructed arteriovenous (AV) grafts connecting the common carotid artery and the external jugular vein in Landrace pigs. After excluding seven pigs for technical failure, cross-sections of graft-venous anastomoses obtained 6 weeks after placing the AV grafts were analysed. Percentage luminal stenosis, ratios of intima to media in whole cross-sections, areas of intima in the peri-junctional areas (within 2 mm above and 2 mm below the graft-venous junction), and the mean thickness of intima within venous sides of cross-sections, were 60.5% (range, 41.5-60.7), 13.0 (range, 8.6-20.4), 23.7 mm(2) (range, 10.8-32.1) and 2.1 mm (range, 1.1-3.0), respectively, in the control group, whereas corresponding median values in the coated group were 10.4% (range, 1.0-17.8), 1.0 (range, 0.7-5.1), 1.6 mm(2) (range, 0.2-8.0) and 0.3 mm (range, 0.1-2.2). All parameters were significantly different between the two groups (P<0.05 by Mann-Whitney test). Paclitaxel-coated ePTFE grafts could prevent neointimal hyperplasia and the stenosis of AV haemodialysis grafts.

Fabrication of a phospholipid membrane-mimetic film on the luminal surface of an ePTFE vascular graft

A stabilized, membrane-mimetic film was produced on the luminal surface of an ePTFE vascular graft by in situ photopolymerization of an acrylate functonalized phospholipid using a fiber optic diffusing probe. The phospholipid monomer was synthesized, prepared as unilamellar vesicles, and fused onto close-packed octadecyl chains that were components of an amphiphilic terpolymer anchored onto the polyelectrolyte multilayer (PEM) by electrostatic interactions. Scanning electron microscopy (SEM) confirmed that gelatin impregnation of the graft followed by the subsequent biomimetic film coating filled in the fibril and node structure of the luminal surface of the ePTFE graft and was smooth. The lipid film displayed an initial advancing contact angle of 44°, which increased to 55° after being subjected to a wall shear rate of 500 s −1 for 24 h at 37 °C in phosphate buffered saline (PBS). Fourier transform (FT-IR) spectroscopy was used to characterize the stages of biomimetic film assembly and confirmed the stability of the film under shear flow conditions. In vivo assessment using a baboon femoral arteriovenous shunt model demonstrated minimal platelet and fibrinogen deposition over a 1-h blood-contacting period. The results of this study confirm the versatility of a biomimetic film coating system by successfully transferring the methodology previously developed for planar substrates to the luminal surface of an ePTFE vascular graft.

Heparin immobilization reduces thrombogenicity of small-caliber expanded polytetrafluoroethylene grafts

The patency of small-diameter expanded polytetrafluoroethylene (ePTFE) grafts for vascular reconstruction is impaired by acute thrombotic occlusion. Prosthetic materials are thrombogenic and cause platelet adhesion and activation of the coagulation cascade. Heparin is a potent anticoagulant drug widely used to prevent and treat thrombosis. A new ePTFE graft with long-term bonding of heparin is now commercially available in several European countries, but a basic analysis of its mechanism of action in humans has never been performed. This study was performed to evaluate the thrombogenicity of heparin-bonded ePTFE grafts compared with standard ePTFE in a newly developed human ex vivo model. Nonanticoagulated blood was drawn from antecubital veins of 10 healthy donors with a 19-gauge needle. The proximal end of a 60-cm ePTFE vascular graft with a diameter of 3 mm was connected to the needle while the distal end was connected to a syringe, which was placed in a syringe pump. Every volunteer served as his or her own control by using a heparin-bonded ePTFE graft on one arm and a standard ePTFE graft on the other arm. The perfusions were performed over 6 minutes with a flow rate of 20 mL/min, corresponding to a shear rate of 74/s. Serial samples were taken at the distal end of the graft for determination of prothrombin fragment 1 + 2, fibrinopeptide A, and P-selectin expression on perfused platelets. Fibrin deposition and platelet deposition were studied by using scanning electronic microscopy. Fibrinopeptide A production over time was significantly reduced on the heparin-bonded ePTFE grafts compared with standard ePTFE grafts (P < .05). There was no increase in the production of prothrombin fragment 1 + 2 or P selectin over time on either type of graft. Scanning electronic microscopy scanning showed platelet deposition and fibrin formation on standard ePTFE grafts, whereas no platelets or fibrin were observed on heparin-bonded ePTFE grafts. Heparin immobilization substantially reduces the thrombogenicity of small-diameter ePTFE in a newly developed human ex vivo model. In this study, we provide evidence that the mechanism of action of the heparin bonding is due not only to anticoagulant but also to antiplatelet effects. Heparin bonding may be an important improvement of ePTFE, resulting in better patency rates for vascular reconstructions.

Biomimetic materials for injectable tissue engineering: studies of acute, lasting and unexpected angiogenesis response

Challenges for therapeutic manipulation of adult angiogenesis with exogenous growth factors are to counteract (1) aberrant vessel growth (2) vessel leakage (3) vessel regression. We describe tissue engineering solutions, based on fibrin or poly ethyleneglycol-peptide implant matrices, for localized and prolonged delivery of VEGF that help ensure localized growth of structurally normal and lasting vessels and minimize adverse side effects. These matrices bind VEGF such that decisions on dosage, location, and duration of released factor are coupled to cellular proteolytic activity at the treatment site, i.e. biological feedback regulation of release. We describe acute angiogenesis response to such schemes of cell-demanded release using video microscopy, morphometry, casting techniques and scanning electron microscopy. Further, we have used biophotonic measurements in transgenic Vegfr2-luc (Xenogen) to correlate transcriptional activation of angiogenesis with immunohistochemical analysis of lasting vessel growth at and around VEGF- releasing implants. We have used VEGF-fibrin matrices applied to the flow surface of synthetic ePTFE grafts in pig trials of spontaneous graft endothelialization. We report an unexpected, untoward effect of VEGF for increasing intimal thickening, indicative of an effect for smooth muscle cell activation. Sponsored by Gebert Rüf Foundation.

Titanium coating improves neo-endothelialisation of ePTFE grafts

Objectives: Patency of small synthetic bypass grafts is inferior to autologous grafts. Titanium coating of vascular grafts has been shown to decrease thrombogenicity, enhance biocompatibility and to promote adhesion of endothelial cells, resulting in improved patency. The aim of this study was to test the short term patency and endothelialisation of novel coating of ePTFE grafts with titanium.

Invited commentary

Bosiers et al herein report the first clinical series of infrainguinal bypass with a new, heparin-bonded, expanded polytetrafluoroethylene (ePTFE) prosthesis. This option has now been added to the smorgasbord of options from which vascular surgeons may choose when performing infrainguinal bypass. The menu includes reversed, nonreversed, and in situ great and short saphenous vein; alternate (arm) vein; Dacron; heparin-bonded Dacron; human umbilical vein (HUV); Distaflo (Bard Peripheral Vascular, Inc, Tempe, Ariz) ePTFE; and standard ePTFE, to which one may add adjuncts such as a Miller cuff, St. Mary’s collar, Taylor patch, or distal arteriovenous fistula. Although this report is interesting and provocative, it represents at most a tantalizing tidbit on the smorgasbord of vascular grafts rather than a substantial main course. The study was conducted in a relatively low-risk group of patients and was limited by small sample size, short follow-up, and lack of a control group. Fifty-five of the 99 procedures were above-knee (AK) femoropopliteal (FP) bypasses, and 58 of the procedures were performed for claudication (Rutherford grade I, category 3); only 16 procedures were performed in patients with rest pain (grade II, category 4), and 26 bypasses were performed in individuals with minor tissue loss (category 5). Among 45 infrageniculate bypasses, the insertion site was the below-knee (BK) popliteal artery in 24 patients and a crural vessel in 21. Ten of 86 patients died during the first follow-up year, and 15 of 99 implanted grafts occluded during the first year after surgery, leaving small numbers of patients and grafts available for even short, 1-year follow-up. Reported, 1-year life-table primary patency rates were 84% for AK FP bypasses and 81% for BK FP grafts. The numbers were so small for the crural subgroup that the standard of error was >10% at both 6 and 12 months, making the Kaplan-Meier curve unreliable. Skeptics will note that almost any material performs well for the first 1 to 3 years in claudicants with an AK popliteal insertion site. At least three prospective, randomized trials have demonstrated equivalence between ePTFE and Dacron for AK FP bypass. Although a single study of 209 patients reported early improvement in FP graft patency for heparin-bonded Dacron compared with standard ePTFE at 3 years, by 5 years, results were equivalent. Randomized prospective trials have demonstrated that vein outperforms all prosthetic conduits for all infrainguinal insertion sites; while the demonstration of vein superiority in the AK position requires 3 to 5 years of follow-up, the superiority of vein over prosthetic has been readily demonstrated for BK FP and femorocrural bypasses with only 1 to 2 years of follow-up. A single study of PTFE with a Miller cuff for BK popliteal bypass reported dramatically improved 2-year patency (52% vs 29%) associated with the addition of a distal cuff. If the vascular surgeon of 2005 were to approach the infrainguinal graft smorgasbord and find that vein is unavailable, what conduit should he select? The present study will not help him reach a decision. Available in vitro animal studies suggest that heparin is detectable for up to 4 weeks on polyester Dacron grafts. Heparin activity has been reported to be measurable for up to 12 weeks on heparin-bonded ePTFE grafts. Whether this possibly longer duration of heparin activity confers increased thromboresistance as well as a patency advantage for heparin-bonded ePTFE grafts is uncertain. The clinical utility of this potentially promising off-the-shelf prosthesis will require prospective, randomized trials. Suitable control groups would include standard ePTFE, PTFE with a distal venous adjunct (cuff, collar, or patch), and perhaps ePTFE with a modified distal cuff such as Distaflo. Given the apparent aversion of vascular surgeons to prospective, randomized trials of infrainguinal bypass grafts, we may have to wait for quite a while before we know. Until then, the conduit choice in the absence of suitable vein remains a highly subjective matter of taste.