Uncoated Grafts Research Articles

A Systematic Review and Meta-Analysis of Heparin-Bonded Expanded Polytetrafluoroethylene Grafts for Below-The-Knee Femoral Bypass Surgery

Heparin-bonded expanded polytetrafluoroethylene (hb-ePTFE) synthetic grafts are an alternative to autologous vein grafts (AVG) for surgical bypass interventions in lower limb peripheral arterial disease (LLPAD). However, the clinical benefits of hb-ePTFE grafts have not been reviewed systematically for patients undergoing below-the-knee (BK) surgical bypass. This study aimed to meta-analyze available data on the utility of hb-ePTFE in patients undergoing BK surgical bypass. Medline, Embase, and Cochrane databases were searched, restricted to material in English with no date restriction. In addition, proceedings from relevant congresses were screened going back 2years. The search was performed in December 2021. Eligible studies included prospective or retrospective comparative studies or prospective single-arm cohorts with an hb-ePTFE arm. Methodological quality was assessed with the ROBINS-I criteria. Outcomes included primary patency, amputation/limb salvage, and overall survival. Clinical outcomes were expressed as event rates. Studies were compared using meta-analysis to generate a standardized mean event rate for each outcome, with its 95% confidence interval (95% CI), using a random-effects model. Following deduplication, 10,263 records were identified and 261 were assessed as full texts. No prospective comparative studies were identified. The level of evidence was uniformly low. Seventeen publications describing data from 9 individual patient cohorts met the inclusion criteria. These cohorts included a total of 1,452 patients undergoing BK surgical bypass with hb-ePTFE. The primary patency rate was 78.9% [95% CI: 72.2-85.7%] at 1year, 68.2% [95% CI: 62.8-73.6%] at 2years, decreasing to 48.0% [95% CI: 27.3-68.7%] at 5years. The secondary patency rate was 84.8% [95% CI: 77.0-92.5%] at 1year and 68.9% [95% CI: 43.0-94.9%] at 3years; the 1-year limb salvage rate was 88.3% [95% CI: 79.6-97.1%] at 1year and 79.0% [95% CI: 56.7-100%] at 3years. In patients undergoing BK bypass surgery, hb-ePTFE synthetic grafts, compared to uncoated grafts, perform well for patency and limb salvage. However, the quality of the evidence is low, and well-performed randomized clinical trials are needed to inform clinical decision-making on the choice of synthetic graft.

Polycatecholamine and gentamicin as modifiers for antibacterial and blood-biocompatible polyester vascular prostheses

Polyester (PET) prostheses are commonly used in reconstructive vascular surgery. The most serious complication after implantation is early or late infection of the graft. Therefore, there is high demand to protect prosthesis against bacterial adhesion and biofilm development. For this reason, in this work PET prostheses were first coated by highly adhesive polycatecholamine layer. The grafts were then coupled with gentamicin and studied in relation to morphological and structural properties, biological safety (contact with blood, reaction of vascular endothelial cells (HUVEC), Danio rerio fish), drug release and antibacterial activity. Among two tested catecholamine monomers, L-DOPA was found to be more effective precursor in this process than dopamine. For L-DOPA, assistance of Cu2+, Mg2+ and Na+ ions seems to increase the amount of further immobilized drug. Coated prostheses exhibited greater human endothelial cell proliferation increase and lower cytotoxic effect than uncoated. The modification reduced the hemolysis observed for pristine commercial graft and limited the rate of abnormalities in D. rerio larvae, confirming the safety of the proposed modification. The coating allowed to double the amount of immobilized antibiotic in comparison with uncoated graft which resulted in increased antibacterial activity and reduced bacterial adhesion against 4 bacterial strains prevalent in biomaterials infections. Overall, poly(L-DOPA)-coatings deposited on PET vascular grafts can effectively functionalize these prostheses for higher safety in biomedical applications.

Controlled autologous recellularization and inhibited degeneration of decellularized vascular implants by side-specific coating with stromal cell-derived factor 1α and fibronectin

Optimized biocompatibility is crucial for the durability of cardiovascular implants. Previously, a combined coating with fibronectin (FN) and stromal cell-derived factor 1α (SDF1α) has been shown to accelerate the in vivo cellularization of synthetic vascular grafts and to reduce the calcification of biological pulmonary root grafts. In this study, we evaluate the effect of side-specific luminal SDF1α coating and adventitial FN coating on the in vivo cellularization and degeneration of decellularized rat aortic implants. Aortic arch vascular donor grafts were detergent-decellularized. The luminal graft surface was coated with SDF1α, while the adventitial surface was coated with FN. SDF1α-coated and uncoated grafts were infrarenally implanted (n = 20) in rats and followed up for up to eight weeks. Cellular intima population was accelerated by luminal SDF1α coating at two weeks (92.4 ± 2.95% versus 61.1 ± 6.51% in controls, p < 0.001). SDF1α coating inhibited neo-intimal hyperplasia, resulting in a significantly decreased intima-to-media ratio after eight weeks (0.62 ± 0.15 versus 1.35 ± 0.26 in controls, p < 0.05). Furthermore, at eight weeks, media calcification was significantly decreased in the SDF1α group as compared to the control group (area of calcification in proximal arch region 1092 ± 517 μm2 versus 11 814 ± 1883 μm2, p < 0.01). Luminal coating with SDF1α promotes early autologous intima recellularization in vivo and attenuates neo-intima hyperplasia as well as calcification of decellularized vascular grafts.

1164. In vitro Antimicrobial Efficacy of Novel Antimicrobial Dacron Vascular Grafts in the Inhibition of Multidrug-Resistant Gram-Negative Biofilm

BackgroundVascular graft infections can be a devastating complication in vascular reconstructive surgery. Management of these infections is highly invasive and includes excision of the graft, debridement of infected material, and in situ reconstruction. There is a need for additional strategies for infection prevention in graft surgeries. The minocycline + rifampin + chlorhexidine (MRCH) triple combination had been previously demonstrated to be effective against biofilm formation in central venous catheters. In this study, we evaluated in vitro effectiveness and durability of MRCH coated Dacron vascular grafts in inhibiting multidrug-resistant Gram-negative biofilm formation.MethodsDacron vascular grafts were coated with MRCH based on a proprietary method. Antimicrobial efficacy at baseline and 3-week durability was assessed using a well-established in vitro biofilm colonization model. Multidrug-resistant Gram-negative pathogens tested include CRE Escherichia coli (EC), MDR Pseudomonas aeruginosa (PS) and CRE Klebsiella pneumoniae (KB). Antimicrobial durability was assessed for grafts that had been eluting in serum for 3 weeks prior to testing. Baseline and 3-week grafts were quantitatively culture to enumerate any biofilm viable biofilm colonization. Uncoated Dacron grafts were used as controls.ResultsAt baseline and 3 weeks MRCH vascular grafts completely inhibited biofilm formation resulting in an 8-log10 reduction in bacterial colonization compared with uncoated grafts.ConclusionMRCH coated Dacron vascular grafts demonstrated in vitro effectiveness for at least 3 weeks in preventing biofilm colonization by multidrug-resistant Gram-negative pathogens. Further in vivo testing is warranted. Disclosures All authors: No reported disclosures.

Heparin-Coated Grafts Reduce Mortality in Pediatric Patients Receiving Systemic-to-Pulmonary Shunts.

We aimed to evaluate the outcomes of systemic-to-pulmonary (SP) shunt procedures utilizing heparin-coated (HC) polytetrafluoroethylene (PTFE) vascular grafts compared to uncoated (non-HC) grafts, in order to observe any benefits in pediatric patients. Our institution switched from using non-HC grafts to HC grafts in March 2011. We conducted a retrospective review of consecutive pediatric patients receiving SP shunts from May 2008 to December 2015. Perioperative variables including baseline characteristics, morbidity, mortality, and blood product utilization were evaluated between the HC and non-HC groups. A total of 142 pediatric patients received SP shunts during the study period: 69 patients received HC shunts and 73 patients received non-HC shunts. The HC group had significantly fewer desaturation or arrest events (P < 0.01), fewer shunt occlusions/thromboses (P < 0.01). There was no statistically significant difference in unplanned reoperations between groups (P = 0.18). The HC group demonstrated significantly lower overall 30-day mortality (P < 0.01), as well as shunt-related mortality (P < 0.01). The HC group had significantly lower postoperative packed red blood cell utilization as compared to the non-HC group (P < 0.01). In this study, pediatric patients receiving HC PTFE grafts in SP shunts demonstrated significantly lower shunt-related mortality. The majority of HC grafts remained patent. These findings suggest that HC grafts used in SP shunt procedures may benefit pediatric patients in terms of efficacy and outcomes.

Biomimetic Heparan Sulfate-Like Coated ePTFE Grafts Reduce In-graft Neointimal Hyperplasia in Ovine Carotids

Thrombogenicity and neointimal hyperplasia are major causes for synthetic vascular graft failure. Bioactive coatings like heparin have improved patency by reducing thrombogenicity, but neointimal hyperplasia still remains an unsolved problem. Surface coatings with heparan sulfate (HS), the major component of the glycocalyx of endothelial cells, have shown reduced platelet and cell adhesion invitro. The aim of the study was to evaluate the invivo surface properties of expanded ePTFE vascular grafts with a semisynthetic HS-like coating (SSHS). ePTFE vascular grafts (n=16, diameter 3.5mm) covalently coated with SSHS were compared with uncoated grafts (n=16) of the same diameter in a carotid interposition model in 16 sheep. The grafts were harvested at 20wk for histological and morphometric analysis. SSHS-coated grafts showed less neointima formation than uncoated grafts (P<0.001). There was no evidence for cell or protein adhesion to SSHS-coated grafts, whereas the surface of uncoated ePTFE grafts was covered with a confluent circular layer of neointima. No difference was found concerning reactions at the anastomotic site of the genuine carotid vessel, both groups displayed neointimal hyperplasia. ePTFE grafts covalently coated with a semisynthetic SSHS-glycosaminoglycan successfully mimicked the endothelial glycocalyx. They displayed excellent antiadhesive properties preventing neointimal formation on the graft surface. The results indicate that a biomimetic SSHS coating may be a useful component of bioengineered grafts and an alternative to synthetic surfaces and endothelial seeding.

Serum albumin coating of demineralized bone matrix results in stronger new bone formation.

Blood serum fractions are hotly debated adjuvants in bone replacement therapies. In the present experiment, we coated demineralized bone matrices (DBM) with serum albumin and investigated stem cell attachment in vitro and bone formation in a rat calvaria defect model. In the in vitro experiments, we observed that significantly more cells adhere to the serum albumin coated DBMs at every time point. In vivo bone formation with albumin coated and uncoated DBM was monitored biweekly by computed tomography until 11 weeks postoperatively while empty defects served as controls. By the seventh week, the bone defect in the albumin group was almost completely closed (remaining defect 3.0 ± 2.3%), while uncoated DBM and unfilled control groups still had significant defects (uncoated: 40.2 ± 9.1%, control: 52.4 ± 8.9%). Higher density values were also observed in the albumin coated DBM group. In addition, the serum albumin enhanced group showed significantly higher volume of newly formed bone in the microCT analysis and produced significantly higher breaking force and stiffness compared to the uncoated grafts (peak breaking force: uncoated: 15.7 ± 4 N, albumin 46.1 ± 11 N). In conclusion, this investigation shows that implanting serum albumin coated DBM significantly reduces healing period in nonhealing defects and results in mechanically stronger bone. These results also support the idea that serum albumin coating provides a convenient milieu for stem cell function, and a much improved bone grafting success can be achieved without the use of exogenous stem cells.

Paclitaxel coating on the terminal portion of hemodialysis grafts effectively suppresses neointimal hyperplasia in a porcine model

The local delivery of paclitaxel onto a graft has been reported to prevent neointimal hyperplasia. Because more than half of vascular stenoses occur within 3 cm of the venous anastomosis, this study tested the effectiveness of a paclitaxel coating restricted to both ends of the expanded polytetrafluoroethylene (ePTFE) graft to reduce the amount of drug delivered. Both ends of ePTFE grafts were coated with paclitaxel at a dose of 0.58 μg/mm(2); the total amount of paclitaxel per graft was 0.66 mg. Paclitaxel-coated hemodialysis grafts 15 cm in length were surgically implanted between the common carotid artery and external jugular vein in female Landrace pigs. The animals were sacrificed 6 weeks after graft placement. Cross sections of the anastomosis sites were analyzed histomorphometrically to measure the ratio of neointimal hyperplasia to the graft area (H/G ratio) and the percentage of luminal stenosis. The experimental results were compared between grafts coated with paclitaxel at the ends only (n = 8), grafts coated over the entire length (n = 6), and uncoated control grafts (n = 6). The mean ± standard error values of the H/G ratios for the arterial anastomosis were 0.82 ± 0.13 (control), 0.41 ± 0.09 (terminal coating), and 0.21 ± 0.04 (whole coating). The values for the venous anastomosis were 0.82 ± 0.12 (control), 0.39 ± 0.11 (terminal coating), and 0.12 ± 0.03 (whole coating). Compared with the uncoated grafts, neointimal hyperplasia was suppressed effectively in the vascular grafts coated terminally with paclitaxel (artery, P = 050; vein, P < .001). However, the suppressive effect was less than that of grafts coated with paclitaxel over the entire length. The percentages of luminal stenosis showed similar tendency to the H/G ratios. Despite a reduced amount of the drug, paclitaxel coating applied to both ends of the ePTFE hemodialysis grafts effectively suppressed neointimal hyperplasia at the sites of anastomosis.

Local hemodynamic disturbance accelerates early thrombosis of small-caliber expanded polytetrafluoroethylene grafts

Small-caliber expanded polytetrafluoroethylene (ePTFE) grafts cannot be used widely in the clinical situation because of early thrombosis and occlusion. This unsolved and under-recognized problem warrants further investigation. Grafts of uncoated ePTFE (n = 6) and anti-CD34-coated ePTFE (n = 6) were implanted unilaterally into the carotid artery in 12 domestic pigs. Ultrasonography was used to test the proximal and distal anastomotic stoma morphology, diameters and blood velocities. A thrombosis instrument was used to examine the blood coagulation state. After seven days, the pigs were sacrificed and the implanted grafts were excised for general and histological analysis. Computational fluid dynamics was used to investigate the blood flow fields of the implanted grafts and to calculate parameters that might be indicative of thrombosis. Thrombosis was detected in 10 of 12 (83.3%) implanted ePTFE grafts, 5 in uncoated grafts and 5 in anti-CD34-coated grafts. Endothelial cell coverage was observed in both uncoated and anti-CD34-coated grafts. No obvious abnormalities in anastomotic stoma or blood coagulation state were observed. Computer-based local hemodynamic simulation showed the low flexibility of synthetic ePTFE grafts caused obvious coarctation. Local wall pressure, velocity and wall shear stress were much higher than in the contralateral normal vessel. The patency of small-caliber ePTFE grafts for clinical use is impaired by early thrombosis due to mixed causes. Local hemodynamic disturbance was the most powerful predictor of early thrombosis. Decreasing local hemodynamic disturbance, improving the quality of anastomotic stoma, selecting reasonable anticoagulation strategies and promoting rapid endothelialization may increase the long-term patency of small-caliber vascular grafts.

Abstract 175: Efficacy of Biomimetic Peptide-Fluorosurfactant Polymer Coated Expanded Poly(tetrafluoroethylene) Vascular Grafts in a Porcine Carotid Artery Interposition Model

Objectives Vascular grafts currently see limited use in small diameter applications due to the prevalence of thrombosis. Patency of ePTFE grafts could be improved by reducing thrombosis via an endothelial cell specific peptide fluorosurfactant polymer (FSP) coating. Methods In this study, ePTFE grafts were coated with cRRE-FSP, RGD-FSP, or Maltose-7 (M7)-FSP, sodded with porcine pulmonary artery endothelial cells (PPAECs), and evaluated in vivo in a porcine carotid artery interposition model. Grafts were excised after one month and evaluated by quantifying thrombosis and intimal hyperplasia and by qualitatively examining inflammation, smooth muscle cell infiltration, and endothelialization. Results Angiography of the grafts after one month showed at least partial patency in all grafts with the exception of one RGD-coated and one uncoated graft. Immunofluorescent staining of cell-sodded grafts showed a complete endothelial layer of adherent and spread PPAECs. Thrombus formation was present in two uncoated grafts and one RGD-coated graft. Intimal hyperplasia comprised mostly of smooth muscle cells was present in all grafts, but developed to the highest extent in RGD-coated grafts. Mean graft occlusion in M7 (24.7%) and cRRE-coated grafts (25.1%) was reduced by half compared to uncoated (58.5%) and RGD-coated grafts (53.9%). Conclusions Increased intimal hyperplasia in RGD grafts suggests that RGD, a prominent cell adhesion peptide, may facilitate ingrowth of more smooth muscle cells compared to the other grafts. These results show that cRRE-FSP coating of ePTFE grafts may reduce thrombosis, making it a promising candidate for improving graft patency.

Serum albumin enhances bone healing in a nonunion femoral defect model in rats: a computer tomography micromorphometry study

Blood-derived proliferative factors such as platelet rich plasma or activated plasma are promising adjuvants for bone grafts. Our earlier studies showed that serum albumin itself can markedly enhance the proliferation of stem cells on bone allograft and postulated that albumin coating alone may improve bone graft integration in vivo. Two femoral defect models were performed in adult male Wistar rats. In the critical size model a six millimetre gap was created in the midshaft of the femur and fixed with plate and screws, while a nonunion model was established by the interposition of a spacer in the osteotomy for four weeks which resulted in compromised healing and nonunion. Albumin coated and uncoated grafts were placed into the defects. Bone healing and morphometry were evaluated by μCT and histology four weeks after implantation of the grafts. In the critical size model none of the bone grafts were able to bridge the defect, and graft resorption was the typical outcome. In the nonunion model regular uncoated grafts had a low union rate (two out of six), which increased markedly when albumin coating was applied (six out of eight). Trabecular thickness and pattern factor improved significantly in the albumin coated group versus uncoated or empty controls. Our results showed that serum albumin coating of bone grafts can enhance the remodelling and efficacy of treatment in a nonunion model.

Prosthetic Vascular Conduit in Contaminated Fields: A New Technology to Decrease ePTFE Infections

Vascular reconstruction using prosthetic materials in contaminated fields can lead to infection, graft loss, and subsequent amputation. We hypothesized that minocycline and rifampin bound to an ePTFE graft using a unique methacrylate technology would provide for resistance from infection and controlled antibiotic elution. Kirby Bauer susceptibility testing was performed on plates overlaid with Staph aureus (SA) and Staph epidermidis (SE) using 6 mm diameter discs of uncoated graft or antibiotic coated graft (ABX). Zones of inhibition (ZIH) were determined after 24 hours. ABX grafts were then placed in a continuous water bath and a recirculating, pulsatile flow device. Susceptibility testing and high performance liquid chromatography with mass spectroscopy was performed to determine graft performance and antibiotic elution rate. ABX grafts had an average ZIH of 35 mm for SA and 44 mm for SE (each P < 0.0001). After the 1 week water bath, the ZIH of the ABX grafts was 23 mm on both the SA and SE plates. The high performance liquid chromatography with mass spectroscopy revealed that after 24 hours, 50 per cent of the antibiotics remained on the graft, and there was a sustained elution for 7 days. Minocycline and rifampin can be bound to ePTFE vascular grafts using a unique methacrylate method. In vitro, the grafts provide a slow elution of antibiotics that provide resistance from infection by SA and SE for up to 2 weeks after graft insertion.

Lateral ridge augmentation using particulated or block bone substitutes biocoated with rhGDF-5 and rhBMP-2: an immunohistochemical study in dogs

The aim of the present study was to immunohistochemically evaluate lateral ridge augmentation using a particulated (BOG) or block (BOB) natural bone mineral biocoated with rhGDF-5 and rhBMP-2 in dogs. Three standardized box-shaped defects were surgically created at the buccal aspect of the alveolar ridge in each quadrant of eight beagle dogs. After 2 months of healing, the chronic-type defects were randomly allocated in a split-mouth design to either (i) BOG or (ii) BOB biocoated with (a) rhGDF-5 or (b) rhBMP-2, respectively. Uncoated grafts served as controls. After 3 and 8 weeks, dissected blocks were prepared for immunohistochemical [osteocalcin (OC)] and histomorphometrical analysis [e.g. area (mm(2)) of new bone fill (BF), newly formed mineralized (MT) and non-mineralized tissue (NMT)]. rhBMP-2 biocoated BOG revealed significantly highest BF and MT values at 3 (upper and lower jaws - UJ/LJ - compared with BOG) and 8 weeks (UJ - compared with rhGDF-5). Biocoating of BOB using both rhGDF-5 and rhBMP-2 resulted in significantly increased MT values at 8 weeks (UJ/LJ - compared with BOB). In all groups, NMT adjacent to BOG and BOB scaffolds revealed pronounced signs of an OC antigen reactivity. Within the limits of the present study, it was concluded that both rhGDF-5 and rhBMP-2 have shown efficacy; however, their bone regenerative effect was markedly influenced by the carrier.

Lateral ridge augmentation using particulated or block bone substitutes biocoated with rhGDF‐5 and rhBMP‐2: an immunohistochemical study in dogs

AbstractObjectives: The aim of the present study was to immunohistochemically evaluate lateral ridge augmentation using a particulated (BOG) or block (BOB) natural bone mineral biocoated with rhGDF‐5 and rhBMP‐2 in dogs.Materials and methods: Three standardized box‐shaped defects were surgically created at the buccal aspect of the alveolar ridge in each quadrant of eight beagle dogs. After 2 months of healing, the chronic‐type defects were randomly allocated in a split‐mouth design to either (i) BOG or (ii) BOB biocoated with (a) rhGDF‐5 or (b) rhBMP‐2, respectively. Uncoated grafts served as controls. After 3 and 8 weeks, dissected blocks were prepared for immunohistochemical [osteocalcin (OC)] and histomorphometrical analysis [e.g. area (mm2) of new bone fill (BF), newly formed mineralized (MT) and non‐mineralized tissue (NMT)].Results: rhBMP‐2 biocoated BOG revealed significantly highest BF and MT values at 3 (upper and lower jaws – UJ/LJ – compared with BOG) and 8 weeks (UJ – compared with rhGDF‐5). Biocoating of BOB using both rhGDF‐5 and rhBMP‐2 resulted in significantly increased MT values at 8 weeks (UJ/LJ – compared with BOB). In all groups, NMT adjacent to BOG and BOB scaffolds revealed pronounced signs of an OC antigen reactivity.Conclusions: Within the limits of the present study, it was concluded that both rhGDF‐5 and rhBMP‐2 have shown efficacy; however, their bone regenerative effect was markedly influenced by the carrier.

Inhibition of experimental neointimal hyperplasia by recombinant human thrombomodulin coated ePTFE stent grafts

The goal of this study was to evaluate the ability of recombinant human thrombomodulin (rTM) to inhibit neointimal hyperplasia when bound to expanded polytetrafluoroethylene (ePTFE) stent grafts placed in a porcine balloon injured carotid artery model. The left carotid artery of male pigs, weighing 25 to 30 Kg, was injured with an angioplasty balloon. Two weeks later either a non-coated standard ePTFE stent graft (Viabahn, 6 x 25 mm, W. L. Gore & Associates) or a rTM coated stent graft was implanted into the balloon-injured segment using an endovascular technique. Carotid angiography was performed at the time of the balloon injury, two weeks later and then at 4 weeks to assess the degree of luminal stenosis. One month after stent graft deployment, the grafts were explanted following in situ perfusion fixation for histological analysis. The specimens were then cross-sectioned into proximal, middle and distal segments, and the residual arterial lumen and intimal to media (I/M) ratios were calculated with computerized planimetry. rTM binding onto ePTFE-grafts was confirmed by functional activation of protein C and histopathology with immuno-scanning electron microscopy, backscatter electron emission imaging and x-ray microanalysis. All seven of the rTM coated stent grafts and six of the seven uncoated stent grafts were patent at the time of explantation. The mean luminal diameter of the rTM coated stents was 93% +/- 2.0% of the original diameter, compared with 67% +/- 23% (P = .006) in the control group. Histological analysis demonstrated that the area obliterated by intimal hyperplasia at the proximal portion of the rTM stent was -27% compared with the control group: (2.73 +/- 0.69 mm(2), vs 3.47 +/- 0.67 mm(2), P <.05). Neointimal hyperplasia is significantly inhibited in ePTFE stent grafts coated with rTM compared with uncoated grafts, as documented by improved luminal diameter by angiography and by computerized planimetry measurements of residual lumen area. These findings suggest that binding of recombinant human thrombomodulin onto ePTFE grafts may improve the long-term patency of covered stents grafts. Decrease of neointimal hyperplasia of the magnitude observed in this study could significantly improve blood flow and patency of small caliber prosthetic grafts. If the durability of these results can be confirmed by long-term studies, this technique may prove useful in preventing graft stenosis and arterial thrombosis following angioplasty or vascular bypass procedures.

Study on Decellularized Porcine Aortic Valve/Poly (3‐hydroxybutyrate‐co‐3‐hydroxyhexanoate) Hybrid Heart Valve in Sheep Model

To overcome shortcomings of current heart valve prostheses, novel hybrid valves were fabricated from decellularized porcine aortic valves coated with poly (3-hydroxybutyrate-co-3-hydroxyhexanoate [PHBHHx]). In the mechanical test in vitro, the biomechanical performance of hybrid valve was investigated. In an in vivo study, hybrid valve conduits were implanted in pulmonary position in sheep without cardiopulmonary bypass. Uncoated grafts were used as control. The valves were explanted and examined histologically and biochemically 16 weeks after surgery. The hybrid valve conduits maintained original shapes, were covered by a confluent layer of cells, and had less calcification than uncoated control. The mechanical test in vitro revealed that PHBHHx coating improved tensile strength. The results in vivo indicated that PHBHHx coating reduced calcification and promoted the repopulation of hybrid valve with the recipient's cells resembling native valve tissue. The hybrid valve may provide superior valve replacement with current techniques.

Coating with paclitaxel improves graft survival in a porcine model of haemodialysis graft stenosis

Most commonly resulting from intimal hyperplasia at the venous anastomosis, stenosis leading to thrombosis is a major cause of failure of polytetrafluoroethylene (PTFE) dialysis grafts. We recently reported that coating haemodialysis grafts with paclitaxel could reduce neointimal hyperplasia. This study tested whether paclitaxel-coating could prolong graft survival in a porcine model. PTFE grafts were double-coated with paclitaxel. Bilateral grafts were created between the carotid arteries and the external jugular veins, and we evaluated graft survival by weekly measurements of blood flow for 12 weeks. We successfully implanted four pairs of paclitaxel-coated grafts and four pairs of control grafts in eight Landrace pigs. One control pig had to be euthanized at 4 weeks after graft placement. The grafts in the other three controls and four paclitaxel pigs survived until harvesting of the grafts. All paclitaxel-coated grafts remained patent for 12 weeks without decrease of blood flow. Median blood flow was 702 ml/min at three weeks and 818 ml/min at 12 weeks after placement. In contrast, the four control grafts lost luminal patency at 5, 6, 6 and 8 weeks, respectively. In Kaplan-Meier analysis, paclitaxel-coated grafts showed better survival than uncoated grafts (P = 0.011). Double-coating with paclitaxel improved graft survival. Coated PTFE grafts may be effective for the prevention of graft failure in patients on haemodialysis.

Novel thromboresistant materials

The development of a clinically durable small-diameter vascular graft as well as permanently implantable biosensors and artificial organ systems that interface with blood, including the artificial heart, kidney, liver, and lung, remain limited by surface-induced thrombotic responses. Recent breakthroughs in materials science, along with a growing understanding of the molecular events that underlay thrombosis, has led to the design and clinical evaluation of a variety of biologically active coatings that inhibit components of the coagulation pathway and platelet responses by surface immobilization or controlled release of bioactive agents. This report reviews recent progress in generating synthetic thromboresistant surfaces that inhibit (1) protein and cell adsorption, (2) thrombin and fibrin formation, and (3) platelet activation and aggregation.

Enhanced intimal thickening of expanded polytetrafluoroethylene grafts coated with fibrin or fibrin-releasing vascular endothelial growth factor in the pig carotid artery interposition model

Intimal hyperplasia and surface thrombogenicity are major factors in the high failure rate of synthetic small-diameter bypass grafts. Vascular endothelial growth factor is a potent stimulus for endothelial growth, and its provision in a fibrin matrix coating at the luminal graft surface may hold a key to spontaneous graft endothelialization and improved graft patency. Pigs underwent bilateral carotid artery interposition of expanded polytetrafluoroethylene grafts either impregnated with fibrin (n = 11)--engineered to locally release vascular endothelial growth factor121 (vascular endothelial growth factor-fibrin; n = 11)--or left uncoated (n = 12). Graft patency was assessed by quantitative carotid angiography followed by graft histomorphometry at the 1-month experimental end point. Patency rates were not significantly different between study groups. Grafts coated with fibrin or vascular endothelial growth factor-fibrin exhibited significantly increased angiographic narrowing at the proximal anastomosis (for both P < .05 vs uncoated) and no difference at the distal anastomosis and the grafts' middle. Histological analysis showed 80% to 90% endothelial coverage and buildup of intima throughout the lengths of all grafts. Examination of the grafts' midportion revealed significantly enlarged neointimal layers of smooth muscle actin-positive cells in grafts coated with vascular endothelial growth factor-fibrin (242 +/- 47 microm2/micron) and fibrin (177 +/- 41 microm2/micron), compared with uncoated grafts (131 +/- 39 microm2/micron) (for both P < .05 vs uncoated). This thickening could not be explained by enhanced inflammation or vessel wall angiogenesis, which were minimal at the experimental end point. Fibrin and vascular endothelial growth factor produced effects deleterious to graft healing, by increasing the narrowing at proximal anastomosis and neointimal growth beyond that seen in uncoated grafts. It may reflect direct activation by exogenous vascular endothelial growth factor of vascular smooth muscle cells.

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.