Treatment of lower limb arterial disease by Dardik graft: It takes one to know one.

OBJECTIVE: To perform a comprehensive literature review on outcomes achieved with the historical Dardik graft, illustrated with a case report of a patient with 13-years primary patency and limb salvage. METHODS: A comprehensive literature review was performed through MedLine (PubMed.gov, U.S. National Library of Medicine, National Institute of Health) from 1976 to 2018 using search terms (Umbilical Vein Graft), (Dardik graft), (Glutaraldehyde stabilized human umbilical vein [HUV]) and (HUV) to collected data on clinical use of HUV. Only papers in English and reporting adequate information about indication for surgery, short- and long-term patency and complication rate were included. RESULTS: Data about a total of 899 patients (977 limbs) were available. Overall, 45% of patients (438 limbs) underwent HUV implantation for critical limb ischemia (rest pain or tissue loss) or for disabling claudication in 12.2% of cases (120 limbs). Others indication for surgery were acute onset limb ischemia, popliteal aneurysms or aneurysmal degeneration of a previously implanted synthetic graft. At a mean follow-up of 4.3 years (range 3-6 years), primary patency and secondary patency were 61.3% and 61%, respectively. Aneurisms formation was detected in 3% of cases (21 limbs), graft's infection in 24.4% of cases (31 limbs) and graft's thrombosis in 25.5% of cases (193 limbs). CONCLUSION: This article provide a historical review of the use, outcomes and complications of HUV. Even though it is no longer commercially available, the knowledge of this type of substitute still remains inspirational for the development of innovative vascular conduits and fundamental for the new generations of physician both in diagnostics and in the management of complications.

Successful Use of the Recanalized Remnant Umbilical Vein as a Patch Graft for Venous Reconstruction in Abdominal Surgery.

Various approaches have been described for the reconstruction of the portal vein (PV), superior mesenteric vein (SMV), and the inferior vena cava (IVC). We present the use of the recanalized remnant umbilical vein in various settings including transplantation, major liver resection, and pancreatic surgery. We retrospectively analyzed four cases, in which a recanalized remnant umbilical vein was used for vascular reconstruction. The graft harvesting, size of the graft, technique of application, and short-term results of vascular patency were studied. A recanalized umbilical vein was successfully harvested from the ligamentum teres hepatis in all patients with 5 cm (median, range 3-7 cm) in length and 1.3 cm (median, range 1.0-1.8 cm) in width. The preparation of the vein was technically feasible and took no more than 5 min in each patient. All grafts were used as a patch for venous reconstruction. In three cases, the graft was used for the reconstruction of the PV or SMV. In one patient, the graft was used to repair a large defect of the IVC. All vascular reconstructions were considered as successful as no bleeding or thrombosis was observed postoperatively. The remnant umbilical vein is a reliable native autologous graft. We found that it is feasible to use this graft as a patch for the reconstruction of the IVC, PV, and SMV.

Flow Preservation of Umbilical Vein for Autologous Shunt and Cardiovascular Reconstruction.

BACKGROUND: Synthetic graft materials are commonly used for shunts and cardiovascular reconstruction in neonates, but are prone to thrombosis and scarring. The umbilical vein is a potential source of autologous, endothelialized tissue for neonatal shunts and tissue reconstruction, but requires preservation before implantation. METHODS: Umbilical cords were collected in UW solution with antibiotics at 4°C until dissection. Umbilical vein segments were tested for burst pressure before and after 2 weeks of preservation. Umbilical veins segments were preserved under static or flow conditions at 4°C in UW solution with 5% human plasma lysate for 7 days. Veins were evaluated with histopathology, scanning electron microscopy, and platelet adhesion testing. RESULTS: Umbilical veins have no difference in burst pressure at harvest (n = 16) compared with 2 weeks of preservation (n = 11; 431 ± 229 versus 438 ± 244 mm Hg). After 1 week, static and flow-preserved veins showed viability of the vessel segments with endothelium staining positive for CD31, von Willebrand factor, and endothelial nitric oxide synthase. Scanning electron microscopy demonstrated preservation of normal endothelial morphology and flow alignment in the flow-preserved samples compared with cobblestone endothelial appearance and some endothelial cell loss in the static samples. Static samples had significantly more platelet adhesion than flow-preserved samples did. CONCLUSIONS: Umbilical veins have adequate burst strength to function at neonatal systemic pressures. Preservation under flow conditions demonstrated normal endothelial and overall vascular morphology with less platelet adhesion compared with static samples. Preserved autologous umbilical veins are potential source for endothelialized shunts or cardiovascular repair tissue for neonates.

Graft type for femoro-popliteal bypass surgery.

BACKGROUND: Femoro-popliteal bypass is implemented to save limbs that might otherwise require amputation, in patients with ischaemic rest pain or tissue loss; and to improve walking distance in patients with severe life-limiting claudication. Contemporary practice involves grafts using autologous vein, polytetrafluoroethylene (PTFE) or Dacron as a bypass conduit. This is the second update of a Cochrane review first published in 1999 and last updated in 2010. OBJECTIVES: To assess the effects of bypass graft type in the treatment of stenosis or occlusion of the femoro-popliteal arterial segment, for above- and below-knee femoro-popliteal bypass grafts. SEARCH METHODS: For this update, the Cochrane Vascular Information Specialist searched the Vascular Specialised Register (13 March 2017) and CENTRAL (2017, Issue 2). Trial registries were also searched. SELECTION CRITERIA: We included randomised trials comparing at least two different types of femoro-popliteal grafts for arterial reconstruction in patients with femoro-popliteal ischaemia. Randomised controlled trials comparing bypass grafting to angioplasty or to other interventions were not included. DATA COLLECTION AND ANALYSIS: Both review authors (GKA and CPT) independently screened studies, extracted data, assessed trials for risk of bias and graded the quality of the evidence using GRADE criteria. MAIN RESULTS: We included nineteen randomised controlled trials, with a total of 3123 patients (2547 above-knee, 576 below-knee bypass surgery). In total, nine graft types were compared (autologous vein, polytetrafluoroethylene (PTFE) with and without vein cuff, human umbilical vein (HUV), polyurethane (PUR), Dacron and heparin bonded Dacron (HBD); FUSION BIOLINE and Dacron with external support). Studies differed in which graft types they compared and follow-up ranged from six months to 10 years.Above-knee bypassFor above-knee bypass, there was moderate-quality evidence that autologous vein grafts improve primary patency compared to prosthetic grafts by 60 months (Peto odds ratio (OR) 0.47, 95% confidence interval (CI) 0.28 to 0.80; 3 studies, 269 limbs; P = 0.005). We found low-quality evidence to suggest that this benefit translated to improved secondary patency by 60 months (Peto OR 0.41, 95% CI 0.22 to 0.74; 2 studies, 176 limbs; P = 0.003).We found no clear difference between Dacron and PTFE graft types for primary patency by 60 months (Peto OR 1.67, 95% CI 0.96 to 2.90; 2 studies, 247 limbs; low-quality evidence). We found low-quality evidence that Dacron grafts improved secondary patency over PTFE by 24 months (Peto OR 1.54, 95% CI 1.04 to 2.28; 2 studies, 528 limbs; P = 0.03), an effect which continued to 60 months in the single trial reporting this timepoint (Peto OR 2.43, 95% CI 1.31 to 4.53; 167 limbs; P = 0.005).Externally supported prosthetic grafts had inferior primary patency at 24 months when compared to unsupported prosthetic grafts (Peto OR 2.08, 95% CI 1.29 to 3.35; 2 studies, 270 limbs; P = 0.003). Secondary patency was similarly affected in the single trial reporting this outcome (Peto OR 2.25, 95% CI 1.24 to 4.07; 236 limbs; P = 0.008). No data were available for 60 months follow-up.HUV showed benefits in primary patency over PTFE at 24 months (Peto OR 4.80, 95% CI 1.76 to 13.06; 82 limbs; P = 0.002). This benefit was still seen at 60 months (Peto OR 3.75, 95% CI 1.46 to 9.62; 69 limbs; P = 0.006), but this was only compared in one trial. Results were similar for secondary patency at 24 months (Peto OR 4.01, 95% CI 1.44 to 11.17; 93 limbs) and at 60 months (Peto OR 3.87, 95% CI 1.65 to 9.05; 93 limbs).We found HBD to be superior to PTFE for primary patency at 60 months for above-knee bypass, but these results were based on a single trial (Peto OR 0.38, 95% CI 0.20 to 0.72; 146 limbs; very low-quality evidence). There was no difference in primary patency between HBD and HUV for above-knee bypass in the one small study which reported this outcome.We found only one small trial studying PUR and it showed very poor primary and secondary patency rates which were inferior to Dacron at all time points.Below-knee bypassFor bypass below the knee, we found no graft type to be superior to any other in terms of primary patency, though one trial showed improved secondary patency of HUV over PTFE at all time points to 24 months (Peto OR 3.40, 95% CI 1.45 to 7.97; 88 limbs; P = 0.005).One study compared PTFE alone to PTFE with vein cuff; very low-quality evidence indicates no effect to either primary or secondary patency at 24 months (Peto OR 1.08, 95% CI 0.58 to 2.01; 182 limbs; 2 studies; P = 0.80 and Peto OR 1.22, 95% CI 0.67 to 2.23; 181 limbs; 2 studies; P = 0.51 respectively)Limited data were available for limb survival, and those studies reporting on this outcome showed no clear difference between graft types for this outcome. Antiplatelet and anticoagulant protocols varied extensively between trials, and in some cases within trials.The overall quality of the evidence ranged from very low to moderate. Issues which affected the quality of the evidence included differences in the design of the trials, and differences in the types of grafts they compared. These differences meant we were often only able to combine and analyse small numbers of participants and this resulted in uncertainty over the true effects of the graft type used. AUTHORS' CONCLUSIONS: There was moderate-quality evidence of improved long-term (60 months) primary patency for autologous vein grafts when compared to prosthetic materials for above-knee bypasses. In the long term (two to five years) there was low-quality evidence that Dacron confers a small secondary patency benefit over PTFE for above-knee bypass. Only very low-quality data exist on below-knee bypasses, so we are uncertain which graft type is best. Further randomised data are needed to ascertain whether this information translates into an improvement in limb survival.

The Usefulness of Patch Repair Using the Repermeabilized Umbilical Vein of the Round Ligament for Hepatobiliary Malignancies.

BACKGROUND: Patients with tumors invading major veins may require combined resection and reconstruction. However, venous reconstruction often demands complex hepatobiliary and vascular surgical procedures. In this study, we report a simple patch repair technique for venous reconstruction using the repermeabilized umbilical vein of the round ligament. METHODS: We reviewed the outcomes of eleven patients who underwent venous wedge resection and patch repair using the repermeabilized umbilical vein of the round ligament at our institution. RESULTS: Procurement of the round ligament and method of making a patch is simple. The duration of anastomosis was approximately 15 min. Eight patients (73%) underwent hepatic resection followed by hepatic vein reconstruction; two (18%) pancreaticoduodenectomy followed by inferior vena cava (IVC) reconstruction; one (9%) hepatic resection followed by IVC reconstruction. Although one reconstructed vein became narrowed, the other ten veins were patent after surgery. CONCLUSIONS: Patch repair using the repermeabilized umbilical vein of the round ligament is a simple and useful technique.

[Reconstruction of the Bile Duct with the Umbilical Vein after Laparoscopic Cholecystectomy]. / Gallengangsrekonstruktion mittels Umbilikalvene nach laparoskopischer Cholezystektomie.

Background: Roux-Y hepaticojejunostomy is currently the standard surgical procedure for the reconstruction of the bile duct after iatrogenic transection in laparoscopic cholecystectomy. However, about 30 % of all hepaticojejunostomies develop a stenosis after some time and in 7 % a cholangiocellular carcinoma occurs. Therefore, alternative procedures have been investigated. Patients: Between September 2009 and October 2013 an iatrogenic bile duct lesion was treated in 6 consecutive patients by using the pedicled umbilical vein. The median follow-up period was 16 months. Methods: In 3 cases, the bile duct lesion was detected during cholecystectomy and reconstructed in the same session. In the other 3 cases, the reconstruction was performed between the fourth and the seventh day after cholecystectomy. The pedicled umbilical vein was used as a patch in 4 cases and as an interposition graft in the other 2 cases. Results: Two out of 6 patients suffered from cholangitis after bile duct reconstruction, which was brought to complete remission by temporary endoscopic dilatation treatment. Conclusion: The use of the pedicled umbilical vein is a new surgical option for the treatment of iatrogenic bile duct lesions and seems to provide advantages over hepaticojejunostomy regarding the development and treatment of anastomotic stenosis and the risk of cholangiocellular carcinoma.

Usefulness of a recanalized umbilical vein for vascular reconstruction in pediatric hepatic surgery.

PURPOSE: Pediatric surgeons currently engage in various abdominal vascular surgeries, which sometimes require vascular conduits or grafts. Herein, we report our experience with patients undergoing vascular reconstruction using a recanalized umbilical vein (rUV) and their long-term outcome. METHOD: Five patients with extrahepatic portal vein obstruction (EHPVO) underwent mesenterico-/porto-left portal vein (PV) bypass surgery using a short rUV conduit with an interposition vein graft. A sixth neonate with a huge hepatic tumor underwent PV reconstruction with anastomosis of rUV to the proximal PV stump following right hepatectomy with partial PV resection. A seventh patient underwent living donor liver transplantation for recurrent hepatoblastoma. The hepatic inferior vena cava (IVC) was resected because of tumor involvement and reconstructed by transposition of the infrahepatic IVC and interposition of rUV obtained from the donor liver graft. RESULTS: Sufficient flow through rUV was achieved and maintained in all patients without any complications during follow-up (0.7-6.9 years). Esophageal varices, splenomegaly, and other laboratory test abnormalities because of portal hypertension disappeared after surgery in patients with EHPVO. CONCLUSION: Our experience confirmed the usefulness and long-term patency of rUV as an entry to the intrahepatic PV and as a free vascular graft to reconstruct PV or IVC.

One-step venous reconstruction using the donor's round ligament in right-lobe living-donor liver transplantation.

We herein report the use of an opened round ligament as a venous patch graft for inferior right hepatic vein (IRHV) reconstruction and anastomosis to the inferior vena cava (IVC) in living-donor liver transplantation (LDLT) using a right-lobe (RL) graft. After laparotomy, the donor's round ligament was harvested and opened, and the semi-transparent umbilical vein, which was 7.0 cm in length and 3.0 cm in width, was carefully trimmed on the back table for use as a patch graft. The right hepatic vein of the graft was anastomosed to the harvested patch, and the IRHV was anastomosed to an independent hole made in the wall on the other side of the patch, to form a bridged vascular patch for anastomosis to the IVC. The interposition graft filled promptly and provided a good outflow from the posterior segment. This is the first report of venous reconstruction using a donor's round ligament graft in RL-LDLT.

Outcomes of complex femorodistal sequential autologous vein and biologic prosthesis composite bypass grafts.

OBJECTIVE: Femorodistal autologous vein bypass proves to be the preferred surgical therapy for long arterial occlusions and provides excellent early and long-term results in critical lower limb ischemia. Whenever vein length was insufficient and two distal outflow arteries were present, a sequential composite bypass configuration was chosen with human umbilical vein (HUV) or ovine collagen prosthesis (Omniflow II; Bio Nova International Pty Ltd, North Melbourne, Australia) as the proximal prosthetic part of the bypass. Single-center experience with this technique regarding limb salvage, graft function, secondary reinterventions, and biodegeneration is presented. METHODS: Between January 1998 and January 2009, 122 consecutive sequential composite bypass operations were performed on 116 patients for short-distance claudication (2), chronic critical ischemia (117), or acute ischemia (3) in the absence of sufficient autologous vein length. HUV was used in 90 cases and Omniflow II in 32 cases. Grafts were followed by duplex scan supplemented by angiography in case of recurrent ischemia with prospective documentation of follow-up data in a computerized vascular database. Retrospective analysis of graft patency, limb salvage, and aneurysmal degeneration of the biologic prosthesis was performed. RESULTS: Mean follow-up was 59 ± 45.5 months (range, 1-161 months). The 30-day mortality was 4.1%. Early postoperative complete or partial bypass thrombosis developed in 16% (20 cases) and required successful revision in 16 cases. During follow-up, 30 complete and 12 partial bypass occlusions occurred, necessitating selective surgical or interventional revision. Primary, primary assisted, and secondary patency rates and the limb salvage rate were 48%, 62%, 71%, and 87%, respectively, after 5 years and 26%, 46%, 54%, and 77%, respectively, after 10 years for all bypasses. Late biodegeneration of HUV prostheses was detected in four instances. CONCLUSIONS: Late graft patency and limb salvage were good. These factors, combined with a tolerable rate of late aneurysmal degeneration, justify the use of biologic vascular conduits and autologous vein for complex femorodistal reconstructions.

Durability of open popliteal artery aneurysm repair.

OBJECTIVE: The objective of this study was to analyze our long-term results after open surgery for popliteal artery aneurysm. METHODS: Records of patients who received surgery between 1998 and 2010 were retrieved from a computerized database and analyzed retrospectively. End points of the study were perioperative mortality and morbidity and patency and limb salvage rate. RESULTS: Two hundred and six popliteal aneurysms (median diameter, 30 mm; interquartile range, 18 mm) were treated (161 elective, 45 emergent) in 154 patients (mean age, 67 ± 11 years) using vein grafts (82%) via the medial approach (92%). Above-knee popliteal artery (45%) and below-knee popliteal artery (65%) were the predominant inflow and outflow vessels. The overall surgical mortality was 2% (2% for elective and 3% for emergent procedures; P = not significant). Primary, assisted primary, and secondary patency rates were 88.1% (73.5%), 92.1% (84.3%), and 96.5% (89.8%) at 5 (at 10) years, respectively, with no significant difference between elective and emergent surgeries. Limb salvage rate was significantly reduced in the emergent group vs the elective group with 91.1% vs 98.6% at 5 and 10 years (P = .0049). The rate of freedom from any reintervention was 84.3% at 5 and 69.8% at 10 years, respectively. CONCLUSIONS: Open surgery for popliteal artery aneurysm is marked by low perioperative mortality and morbidity and provides excellent long-term results.

Percutaneous revascularization of reoccluded meso-Rex shunts in extrahepatic portal vein obstruction.

Extrahepatic portal vein (PV) obstruction (EHPVO) is a rare disorder in early childhood with unknown incidence and mostly unknown etiology. In children with EHPVO, the hepatopedal flow of the mesenteric venous blood is hindered by an obstruction of the PV resulting in prehepatic portal hypertension. The curative treatment with a meso-Rex shunt connects the superior mesenteric vein to the left PV by a venous autograft. Despite good primary patency, reocclusion of a meso-Rex bypass and its treatment can be challenging. We present 2 patients with EHPVO with subtotal functional occlusion of a meso-Rex shunt treated by percutaneous interventions with short- and mid-term follow-up.

All-in-one sleeve patch graft venoplasty for multiple hepatic vein reconstruction in living donor liver transplantation.

OBJECTIVES: This paper presents an innovative technique to address complex multiple hepatic vein (HV) reconstruction in right lobe graft living donor liver transplantation (RL-LDLT). METHODS: A patient with hepatitis C virus-related cirrhosis underwent RL-LDLT. The graft had seven HVs, including: the right HV (17 mm); one segment VII HV (11 mm); two segment VI HVs (6 mm and 16 mm), and three segment V HVs. The graft weighed 663 g (53% of standard liver volume; ratio of graft weight to recipient body weight: 0.96). Each HV had significant drainage territory requiring reconstruction. A cryopreserved iliac vein graft was used to create a sleeve patch to incorporate the HV openings. The holes were anastomosed to their corresponding HV tributaries using continuous 6-0 polydioxanone (PDS) sutures. Two of the three segment V HVs were combined using a smaller iliac vein patch, which was anastomosed in an end-to-side fashion to a previously harvested recipient umbilical vein interposition graft. The other end of the umbilical vein graft was anastomosed to the larger iliac vein sleeve patch. RESULTS: Overall, six HV openings were incorporated in one sleeve patch to allow a single wide anastomosis with the recipient inferior vena cava. Doppler ultrasound after reconstruction showed adequate flow patterns in all the HVs. CONCLUSIONS: All-in-one sleeve patch graft venoplasty simplifies the reconstruction of multiple HVs and reduces warm ischaemia time in RL-LDLT with excellent outcomes.

Graft type for femoro-popliteal bypass surgery.

BACKGROUND: Femoro-popliteal bypass is implemented to save limbs that might otherwise require amputation, in patients with ischaemic rest pain or tissue loss; and to improve walking distance in patients with severe life-limiting claudication. Contemporary practice involves using autologous vein, polyterafluoroethylene (PTFE) or Dacron as a bypass conduit.This is an update of a Cochrane review first published in 1999 and previously updated in 2002. OBJECTIVES: The objective of this review was to determine the most effective type of graft for femoro-popliteal bypass surgery. SEARCH STRATEGY: The Cochrane Peripheral Vascular Diseases Group searched their Specialised Register (last searched January 2010) and the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2010, Issue 1 for last search). The authors searched reference lists of relevant articles, and handsearched conference proceedings from the British and European Vascular Surgical Societies. SELECTION CRITERIA: Randomised trials comparing femoro-popliteal grafts. DATA COLLECTION AND ANALYSIS: Two authors (CT and ADM) screened studies, extracted data and assessed trials. MAIN RESULTS: Thirteen randomised control trials were included with a total of 2313 patients (1955 above knee, 358 below knee bypass surgery). Seven graft types were compared (reversed and in situ autologous vein, PTFE with and without vein cuff, human umbilical vein (HUV), Dacron and heparin bonded Dacron (HBD).Above the knee, there was a benefit in primary patency for autologous vein over PTFE (P = 0.0001) and HUV (P = 0.0003) by 60 months. Dacron showed primary patency benefit over PTFE by 24 months (P = 0.02), continuing to 60 months (P = 0.02). HUV also showed benefit over PTFE by 24 months (P = 0.0003) in one trial. Below the knee, in the one trial there was a significant benefit in primary patency for PTFE with a vein cuff when compared to PTFE alone at all time intervals to 24 months (P = 0.03).Limited data were available for limb survival. Antiplatelet and anticoagulant protocols varied extensively between trials, and in some cases within trials. AUTHORS' CONCLUSIONS: There was a clear primary patency benefit for autologous vein when compared to synthetic materials for above knee bypasses. In the long term (five years) Dacron confers a small primary patency benefit over PTFE for above knee bypass. PTFE with a vein cuff improved primary patency when compared to PTFE alone for below knee bypasses. Further randomised data is needed to ascertain whether this information translates into improvement in limb survival.

Mesoportal bypass for extrahepatic portal vein obstruction in children: close to a cure for most!

AIM: Extrahepatic portal vein obstruction (EPVO) is a common cause of portal hypertension in children and can lead to life-threatening bleeding, thrombocytopenia, and coagulation disorders. Mesoportal bypass (MPB) restores normal physiologic portal flow to the liver and corrects portal hypertension. There is, however, little long-term outcome data after MPB. The aim of our study was to analyze the long-term outcome after MPB in children. METHODS: Retrospective single-center review of all MPB with more than 5-year follow-up was performed in children between 1998 and 2003. RESULTS: Thirty children underwent MPB, which was successful in 29. Long-term follow-up is available for 24. Median age at the time of bypass was 8.5 years (range, 0.4-14.2 years). Material used for bypass was as follows: left internal jugular vein (n = 20), recanalized umbilical vein (n = 2), gastric vein, and a large colic vein (n = 2). Median time since MPB is 8 years (range, 5.3-8.8 years). One MPB using recanalized umbilical vein thrombosed at 4 months but was successfully refashioned using Gortex. One MPB with left internal jugular vein was thrombosed at 1 year after cardiac surgery. Overall, 23 of 24 children have a patent bypass and resolution of portal hypertension. All showed an decrease in spleen size. Recurrent blood flow in the cavernoma with secondary increase in spleen size occurred in 5 children (median time, 3.4 years after MPB). Further evaluation of these 5 revealed no recurrence of portal hypertension. CONCLUSION: The MPB provides long-term correction of portal hypertension owing to EPVO. Where technically feasible, MPB is the preferred surgical procedure for treatment of EPVO.

The human umbilical vein with Wharton's jelly as an allogeneic, acellular construct for vocal fold restoration.

This study investigated the potential of the decellularized human umbilical vein (HUV) as an allogeneic, acellular extracellular matrix (ECM) scaffold for engineering the vocal fold lamina propria in vitro. HUV specimens with Wharton's jelly on the abluminal surface were uniformly dissected from native umbilical cords using an automated procedure and subjected to a novel saline-based decellularization treatment for removal of potentially antigenic epitopes. Human vocal fold fibroblasts from primary culture were seeded onto the resulting acellular constructs and cultured for 21 days. The structures of decellularized and fibroblast-repopulated HUV constructs and the attachment, proliferation, and infiltration of fibroblasts were examined with light microscopy and scanning electron microscopy. Changes in the relative densities of collagen in the constructs associated with decellularization and recellularization were quantified using digital image analysis. In addition, fibroblasts infiltrating the scaffolds were released by cell recovery and quantified by counting. Viscoelastic properties of the scaffolds were measured using a linear, simple-shear rheometer at phonatory frequencies. Results showed that an acellular ECM construct with an intact three-dimensional structure of Wharton's jelly was fabricated. Vocal fold fibroblasts readily attached on the abluminal surface of the construct with high viability, with significant cellular infiltration up to approximately 600 microm deep into the construct. A significant increase in collagen expression was observed with recellularization. The elastic modulus and dynamic viscosity of the fibroblast-repopulated scaffolds were comparable to those of the human vocal fold lamina propria. These findings supported the potential of the construct as a possible surgical allograft for vocal fold restoration and reconstruction.

The human umbilical vein: a novel scaffold for musculoskeletal soft tissue regeneration.

The umbilical cord is a biological tissue that is readily available and is usually discarded. In this study, we investigate the potential of making use of part of the human umbilical cord, in particular the umbilical vein, as a functional tissue engineering scaffold. Previous studies suggested the use of the human umbilical vein (HUV) as an acellular vascular grafting material. We propose taking advantage of the longitudinal mechanical properties of the HUV to use it as a scaffold material for musculoskeletal soft tissue regeneration. HUVs were mechanically dissected from 8.5-cm sections of fresh human umbilical cords. The sections were inverted such that the luminal side formed the exterior surface. HUVs were then decellularized, and filled with mesenchymal stem cells (MSCs) suspended in a type I collagen hydrogel. Seeded HUVs were cultured for periods of up to 2 weeks. After 2 weeks of culture, results showed a significant increase in cell number reaching almost three times the original inoculation density. Histological analysis revealed cell integration and migration into the HUV scaffold and extensive remodeling of extracellular matrix. Mechanically, the ultimate tensile stress doubled, and elastic modulus values were almost 2.7-fold higher. Given the differentiation capacity of the MSCs, along with the appropriate biochemical and biomechanical environment, the seeded HUV has a potential for ligament or tendon regeneration.

A self-renewing, tissue-engineered vascular graft for arterial reconstruction.

OBJECTIVE: Various tissue-engineered vascular grafts have been studied to overcome the clinical disadvantages of conventional prostheses. Previous tissue-engineered vascular grafts have generally required preoperative cellular manipulation or use of bioreactors to improve performance, and their mechanical properties have been insufficient. We focused on the concept of in situ cellularization and developed a tissue-engineered vascular graft for arterial reconstruction that would facilitate renewal of autologous tissue without any pretreatment. METHODS: The graft comprised an interior of knitted polyglycolic acid compounded with collagen to supply a scaffold for tissue growth and an exterior of woven poly-L-lactic acid for reinforcement. All components were biocompatible and biodegradable, with excellent cellular affinity. The grafts, measuring 10 mm in internal diameter and 30 mm in length, were implanted into porcine aortas, and their utility was evaluated to 12 months after grafting. RESULTS: All explants were patent throughout the observation period, with no sign of thrombus formation or aneurysmal change. Presence in the neomedia of endothelialization with proper integrity and parallel accumulation of functioning smooth muscle cells, which responded to vasoreactive agents, was confirmed in an early phase after implantation. Sufficient collagen synthesis and lack of elastin were quantitatively demonstrated. Dynamic assessment and long-term results of the in vivo study indicated adequate durability of the implants. CONCLUSION: The graft showed morphologic evidence of good in situ cellularization, satisfactory durability to withstand arterial pressure for 12 postoperative months, and the potential to acquire physiologic vasomotor responsiveness. These results suggest that our tissue-engineered vascular graft shows promise as an arterial conduit prosthesis.

Human umbilical vein versus heparin-bonded polyester for femoro-popliteal bypass: 5-year results of a prospective randomized multicentre trial.

PURPOSE: To compare long-term patency of Heparin-Bonded Dacron (HBD) and Human Umbilical Vein (HUV) vascular prostheses in above-knee femoro-popliteal bypass surgery. DESIGN: A prospective randomized multi-centre clinical trial. PATIENTS AND METHODS: Femoro-popliteal bypasses were performed in 129 patients between 1996 and 2001. After randomization 70 patients received an HUV and 59 an HBD prosthesis. Patients were followed up every three months during the first postoperative year and yearly thereafter. The median follow-up was 60 months (range 3-96 months). Graft occlusions were detected by duplex scanning, angiography or surgical exploration. RESULTS: The cumulative primary patency rates were 79%, 66% and 58% at 1, 3 and 5 years postoperatively. Primary patency rates for HUV were 74%, 64% and 58% at 1, 3 and 5 years and 84%, 68% and 58% for HBD, respectively (log-rank test, p=0.745). Overall secondary patency rates were 82%, 72% and 61% at 1, 3 and 5 years postoperatively. The overall cumulative limb salvage at 5 years follow-up was 89% (CI 80%-91%) and was not dependent on graft type. Smoking (p=0.019), number of patent crural arteries (p=0.030) and previous cerebro-vascular events (p=0.030) were significant predictors of graft occlusion. CONCLUSION: There was no difference in long-term graft performance between HUV and HBD for above knee infrainguinal bypass.

Femoropopliteal prosthetic bypass with glutaraldehyde stabilized human umbilical vein (HUV).

OBJECTIVE: Femoropopliteal bypass still is the standard surgical therapy for disabling claudication and critical ischemia. When autologous vein is not suitable synthetic or biological prostheses may be considered. Second generation glutaraldehyde tanned human umbilical vein (HUV) graft was chosen for above and below knee femoropopliteal bypass when autologous vein was not available. A single center experience regarding long-term graft function, secondary reinterventions, and potential biodegeneration of the HUV is presented. METHODS: Between January 1994 and January 2005, 211 consecutive femoropopliteal bypass operations with HUV (65 above knee and 146 below knee) were performed in 197 patients for disabling claudication (57), chronic critical ischemia (130), popliteal artery aneurysm (9), acute ischemia (14), or aneurysmal degeneration of a synthetic graft (1) in the absence of suitable ipsilateral great saphenous vein. Grafts were followed with duplex scan supplemented by additional angiography in case of recurrent ischemia with prospective documentation of follow-up data in a computerized vascular database. Surveillance of the HUV included routine evaluation of potential biodegeneration with duplex scan. Retrospective analysis of graft patency, limb salvage, and signs of aneurysmal degeneration was performed. RESULTS: Mean (median) follow-up was 44 (35) months (range 1 to 143 months). Thirty-day mortality was 2.4%. Early postoperative bypass thrombosis after a median of 4 days postoperatively (0 to 30 days) prompted revision with thrombectomy in 16% of cases. Besides late bypass thrombosis in 14.7%, additional operative or endovascular reinterventions during follow-up to maintain or restore graft patency was necessary in 8.5% of bypasses. Primary, primary assisted, secondary patency rate, and limb salvage rate after 5 years were 54%, 63%, 76%, and 92%, respectively, for all bypasses with no significant difference between above and below knee anastomosis. Duplex scan identified segmental aneurysmal degeneration in six grafts, which led to operative reintervention in three cases. The rate of detected aneurysm for grafts patent for more than three years was 7% with a rate of reintervention for aneurysm of 3.5%. CONCLUSION: Although a considerable rate of early thrombotic occlusions occurred, excellent secondary graft patency and limb salvage combined with a tolerable rate of late aneurysmal degeneration detected by means of duplex scan surveillance justify the use of the HUV in femoropopliteal bypass surgery when ipsilateral autogenous vein is not suitable.