First Clinical Experience of Venous Reconstruction With Autologous Vascular Prosthesis From the Sickle Ligament of the Liver With Partial Portosystemic Bypass Surgery

Aim of study. Presentation of our own first clinical experience of venous reconstruction in portosystemic bypass surgery with the use of autologous vascular prostheses of the falciform ligament of the liver in the splenorenal position in a patient with portal hypertension syndrome in the outcome of liver cirrhosis of viral etiology.Material and methods. Clinical observation of a patient born in 1978 with a diagnosis of cirrhosis of the liver of viral etiology (HCV) Child-Pugh A (6). MELD 10 points. Inactive phase. Intrahepatic portal hypertension syndrome. Esophageal varices grade III according to A. G. Scherzinger, gastric varices type I (GOV1) according to Sarin. Condition after repeated recurrent esophageal-gastric bleeding. Due to the high risk of another bleeding, as a secondary prevention of esophageal-gastric bleeding, partial splenorenal anastomosis of “H” - type was performed with the use of an autologous vascular prosthesis of the falciform ligament of the liver in the splenorenal position.Results. A flap measuring 60.0x20.0 mm was cut from the falciform ligament of the patient’s liver. From the latter, after adjusting the size of the graft to the individual needs of the patient, an autologous conduit was formed. It was used as an insert in the formation of an “H” - type splenorenal anastomosis with the imposition of two end-to-side anastomoses between the splenic vein and one end of the conduit and between the left renal vein and the other end of the conduit. The patency of the anastomosis was checked using intraoperative sonography. In a satisfactory condition, the patient was discharged for outpatient follow-up treatment at the place of residence. At the moment of writing the article, the follow-up period was 8 months. The bleeding did not recur. No varicose veins were found in the esophagus and stomach during control endoscopic examinations. The patency of the splenorenal shunt was confirmed by ultrasound dopplerography.Conclusion. The first clinical experience of venous reconstruction with portosystemic bypass surgery using as a possible replacement of autologous vascular prostheses of the falciform ligament of the liver in the splenorenal position in a patient with portal hypertension syndrome in the outcome of cirrhosis of the liver of viral etiology gives hope for the possibility of further successful testing of this method of splenorenal bypass surgery to reduce the risk of bleeding from varicose veins.

Vascular Polyurethane Prostheses Modified with a Bioactive Coating—Physicochemical, Mechanical and Biological Properties

This study describes a method for the modification of polyurethane small-diameter (5 mm) vascular prostheses obtained with the phase inversion method. The modification process involves two steps: the introduction of a linker (acrylic acid) and a peptide (REDV and YIGSR). FTIR and XPS analysis confirmed the process of chemical modification. The obtained prostheses had a porosity of approx. 60%, Young’s Modulus in the range of 9–11 MPa, and a water contact angle around 40°. Endothelial (EC) and smooth muscle (SMC) cell co-culture showed that the surfaces modified with peptides increase the adhesion of ECs. At the same time, SMCs adhesion was low both on unmodified and peptide-modified surfaces. Analysis of blood-materials interaction showed high hemocompatibility of obtained materials. The whole blood clotting time assay showed differences in the amount of free hemoglobin present in blood contacted with different materials. It can be concluded that the peptide coating increased the hemocompatibility of the surface by increasing ECs adhesion and, at the same time, decreasing platelet adhesion. When comparing both types of peptide coatings, more promising results were obtained for the surfaces coated with the YISGR than REDV-coated prostheses.

In vivo performance of electrospun tubular hyaluronic acid/collagen nanofibrous scaffolds for vascular reconstruction in the rabbit model

One of the main challenges of tissue-engineered vascular prostheses is restenosis due to intimal hyperplasia. The aim of this study is to develop a material for scaffolds able to support cell growth while tolerating physiological conditions and maintaining the patency of carotid artery model. Tubular hyaluronic acid (HA)-functionalized collagen nanofibrous composite scaffolds were prepared by sequential electrospinning method. The tubular composite scaffold has well-controlled biophysical and biochemical signals, providing a good matrix for the adhesion and proliferation of vascular endothelial cells (ECs), but resisting to platelets adhesion when exposed to blood. Carotid artery replacement experiment from 6-week rabbits showed that the HA/collagen nanofibrous composite scaffold grafts with endothelialization on the luminal surface could maintain vascular patency. At retrieval, the composite scaffold maintained good structural integrity and had comparable mechanical strength as the native artery. This study indicating that electrospun scaffolds combined with cells may become an alternative to prosthetic grafts for vascular reconstruction. Graphical Abstract

Antimicrobial vascular grafts: experimental development and implementation in clinical practice

Prosthetic vascular graft infections, followed by severe complications and high mortality rates, remain one of the main issues in cardiovascular surgery. Therefore, the development of antimicrobial coating for vascular prostheses that is capable of preventing the infection is a very relevant field. This review outlines the main factors of development of antibiotic-resistant bacteria, the main directions in the development of vascular prostheses with an antimicrobial coating, and the prospects for the application of antimicrobial peptides and cationic amphiphiles as antimicrobial coating to develop an infection-resistant vascular prosthesis.

Impact of Modification on the Energy Characteristics of Surfaces and Matrix Properties of the New Effective Polymer Vascular Implants

New tissue-engineered vascular prostheses of small diameter (4mm) based on biodegradable polymer backbone – poly (ε-caprolactone) (PCL) and its composition with poly (3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV/ PCL) were created. The full cycle of surface modification of the backbone with polyvinylpyrrolidone and drugs permitted to increase significantly the atrombogenic and antimicrobial properties of prostheses and provide its effective matrix properties. Both types of the developed constructs are suitable for testing in vivo. The energy characteristics of the prosthesis surfaces at the different interfaces were determined. It was established that the value of the energy of the "polymer, saturated with octane/water" interface can be used as a parameter for predicting cell adhesion and proliferation in the case when it is difficult to determine or to distinguish the energy characteristics of the surfaces of tissue-engineered materials at the interface with air.

Results of long-term patency of small-diameter biodegradable vascular prostheses with atrombogenic drug coating of sheep model

Background. Preclinical tests of biodegradable small diameter vascular prostheses on a sheep model have been carried out.Aim. To assess the results of long-term patency and remodeling of biodegradable vascular prostheses based on polyhydroxybutyrate / valerate and polycaprolactone with an atrombogenic drug coating in a large laboratory animal model.Methods. We researched vascular prostheses made of polyhydroxybutyrate / valerate and polycaprolactone (PHBV/PCL) 4 mm in diameter with layer-by-layer vascular endothelial growth factor incorporated into the polymer framework, the main fibroblast growth factor, chemoattractant molecule containing SDF-1a (GFmix) surface, and additional modifying drug surface heparin and iloprost (PHBV/PCL/ GFmix/Heparin/Iloprost). Animals with implanted synthetic Gore-Tex vascular grafts with a diameter of 4 mm were included into a comparison group.Results. After one day of implantation it was revealed that the patency of biodegradable PHBV/PCL/GFmix/Heparin/Iloprost prostheses was 62.5%, while synthetic Gore-Tex prostheses were thrombosed in 100% of cases. At the same time, after 18 months of implantation, the patency of biodegradable vascular PHBV/PCL/ GFmix/Heparin/Iloprost prostheses decreased to 50%. Passable drug-eluting polymer grafts were completely resorbed after 18 months of implantation, and aneurysmically expanded newly formed vascular tissue was formed in their place.Conclusion. Vascular prostheses made of polyhydroxybutyrate/valerate and polycaprolactone showed better long-term patency results than synthetic prostheses used in the clinical practice. However, the strengthening of the external framework of the prostheses is required in order to prevent the formation of aneurysms.

Development of personalized cell-populated vascular graft in vitro

Aim. To create a personalized cell-populated small-diameter vascular prosthesis in a pulsating bioreactor.Methods. Tubular grafts were made by electrospinning from mixtures of biodegradable polymers, poly (3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) and poly(εcaprolactone) (PCL). The inner surface is modified with fibrin. Tubular scaffolds were colonized with cultured colony-forming endothelial cells and grown under static conditions for 2 days. Then, the cell-populated prostheses continued to be cultivated for 5 days in a pulsating bioreactor system with a final shear stress of 2.85 dynes/cm².Results. The advantages of the cultivation of cell-populated vascular prostheses in a pulsating bioreactor have been revealed. The selected mode of cultivation of cellpopulated vascular prostheses under conditions of a pulsating flow with a shear stress of 2.85 dynes/cm² did not have a damaging effect on the integrity of the endothelial monolayer. Moving unidirectional mechanical stimuli of chaotic orientation fibers of F-actin changed to a predominant orientation in the direction of flow, and also increased the expression of F-actin, Talin focal adhesion protein, and specific endothelial markers CD309, CD31, vWF.Conclusion. The creation of a personalized cell-populated small-diameter vascular prosthesis with a functional endothelial monolayer is possible due to the use of autologous endothelial cells, autologous fibrin, and cultivation under conditions of a pulsating flow.

Tissue-Engineered Carotid Artery Interposition Grafts Demonstrate High Primary Patency and Promote Vascular Tissue Regeneration in the Ovine Model

Tissue-engineered vascular graft for the reconstruction of small arteries is still an unmet clinical need, despite the fact that a number of promising prototypes have entered preclinical development. Here we test Poly(3-hydroxybutyrate-co-3-hydroxyvalerate)Poly(ε-caprolactone) 4-mm-diameter vascular grafts equipped with vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and stromal cell-derived factor 1α (SDF-1α) and surface coated with heparin and iloprost (PHBV/PCL[VEGF-bFGF-SDF]Hep/Ilo, n = 8) in a sheep carotid artery interposition model, using biostable vascular prostheses of expanded poly(tetrafluoroethylene) (ePTFE, n = 5) as a control. Primary patency of PHBV/PCL[VEGF-bFGF-SDF]Hep/Ilo grafts was 62.5% (5/8) at 24 h postimplantation and 50% (4/8) at 18 months postimplantation, while all (5/5) ePTFE conduits were occluded within the 24 h after the surgery. At 18 months postimplantation, PHBV/PCL[VEGF-bFGF-SDF]Hep/Ilo grafts were completely resorbed and replaced by the vascular tissue. Regenerated arteries displayed a hierarchical three-layer structure similar to the native blood vessels, being fully endothelialised, highly vascularised and populated by vascular smooth muscle cells and macrophages. The most (4/5, 80%) of the regenerated arteries were free of calcifications but suffered from the aneurysmatic dilation. Therefore, biodegradable PHBV/PCL[VEGF-bFGF-SDF]Hep/Ilo grafts showed better short- and long-term results than bio-stable ePTFE analogues, although these scaffolds must be reinforced for the efficient prevention of aneurysms.

The novel hybrid polycarbonate polyurethane / polyester three-layered large-diameter artificial blood vessel

Background The most common materials of artificial blood vessels are polyethylene terephthalate and polytetrafluoroethylene. But polycarbonate polyurethane (PCU) is an ideal material for vascular prostheses because of their excellent characteristics. As far as we know, our artificial blood vessel is the first type of hybrid PCU/polyester three-layered large-diameter artificial blood vessel in the world. Objective The purpose of this preclinical animal experiment is to evaluate the hemocompatibility, histocompatibility, effectiveness, and safety of the three-layered large-diameter artificial blood vessel in sheep. Methods The artificial blood vessels took place of the initial segments of the sheep’s thoracic aorta by end-to-end anastomosis. Results All of the 14 sheep are male, their average body weight (BW) was 30.57 ± 3.95 kg. All 14 artificial blood vessels successfully replaced the thoracic aortas. 5 sheep did not survive to the end of the experiment, while the remaining 9 sheep did. After the surgery, the blood biochemical and blood routine indicators fluctuate slightly within the normal range. The angiography showed that the implanted artificial blood vessels were unobstructed without obvious stenosis or expansion. 24 weeks after surgery, the lumen surfaces of the artificial blood vessels were covered by endothelia in different degrees, and the average endothelialization rate was 69.44% (range: 20% to 100%). Conclusions This artificial blood vessel is the first to use PCU in large-diameter artificial vascular grafts. It has excellent blood compatibility, wonderful biocompatibility, high endothelialization rate, and 100% patency.