Implantation Of Vascular Grafts Research Articles

Regional Differences in Vascular Graft Degradation and Regeneration Contribute to Dilation.

Severe coronary artery disease is often treated with a coronary artery bypass graft using an autologous blood vessel. When this is not available, a commercially available synthetic graft can be used as an alternative but is associated with high failure rates and complications. Therefore, the research focus has shifted toward the development of biodegradable, regenerative vascular grafts that can convert into neoarteries. We previously developed an electrospun tropoelastin (TE)-polyglycerol sebacate (PGS) vascular graft that rapidly regenerated into a neoartery, with a cellular composition and extracellular matrix approximating the native aorta. We noted, however, that the TE-PGS graft underwent dilation until sufficient neotissue had been regenerated. This study investigated the mechanisms behind the observed dilation following TE-PGS vascular graft implantation in mice. We saw more pronounced dilation at the graft middle compared with the graft proximal and graft distal regions at 8 weeks postimplantation. Histological analysis revealed less degradation at the graft middle, although the remaining graft material appeared pitted, suggesting compromised structural and mechanical integrity. We also observed delayed cellular infiltration and extracellular matrix (ECM) deposition at the graft middle, corresponding with the area's reduced ability to resist dilation. In contrast, the graft proximal region exhibited greater degradation and significantly enhanced cellular infiltration and ECM regeneration. The nonuniform dilation was attributed to the combined effect of the regional differences in graft degradation and arterial regeneration. Consideration of these findings is crucial for graft optimization prior to its use in clinical applications.

Preventing Sheep Carotid Artery Spasm for Vascular Graft Surgery and Computed Tomography Angiography.

The development of small-diameter vascular grafts requires testing in large animal models before advancing to clinical trials. Vascular graft interposition implantation in sheep carotid arteries (CAs) is the most widely used model, but ovine CAs are prone to severe spasm following surgical manipulation, potentially impairing graft performance assessment. There is paucity in the literature on reducing sheep CA spasm using effective vasodilator therapeutic protocols. In this study, four healthy Merino cross White Suffolk wethers (1-2 years, 52.1 ± 0.8 kg) underwent CT angiography and CA graft surgery. CT angiography using iodinated contrast agent was performed with innominate artery access through the CA or ascending aortic arch access through the femoral artery. Sheep then underwent right CA sham surgery or left CA vascular graft implantation. A variety of vasodilators, including papaverine, sodium nitroprusside, verapamil, and their combination, were tested for preventing or treating CA spasms intraoperatively. Blood flow was reassessed immediately after CA surgery using CT angiography. The results showed that innominate artery access through the CA for CT angiography in sheep induced presurgical CA spasm with reduced arterial flow. Conversely, ascending aortic arch access through the femoral artery for CT angiography did not cause CA spasm and maintained arterial flow. During CA graft surgery, surgical trauma induced CA spasm, which was prevented by localized intra-arterial administration of vasodilators papaverine hydrochloride and verapamil before significant surgical manipulation.

ИЗМЕНЕНИЯ БИОХИМИЧЕСКИХ ПОКАЗАТЕЛЕЙ КРОВИ У КРЫС ЛИНИИ WISTAR ПОСЛЕ ИМПЛАНТАЦИИ ФРАГМЕНТОВ СОСУДИСТЫХ ПРОТЕЗОВ

Background. This article deals with the use of biological vascular grafts made from bovine xenopericardium as a plastic material for reconstructive operations on the great vessels, which is one of the most important topics in modern vascular surgery. Aim. To compare changes in blood biochemical parameters in Wistar rats after implantation of fragments of biological and synthetic vascular grafts. Material and methods. The experimental study was performed on male laboratory Wistar rats (n = 50). The animals were divided into two groups: group 1 included 25 animals with implantation of a Dacron vascular graft; group 2 was composed of 25 animals with implantation of a vascular graft made from bovine xenopericardium. Blood samples from the laboratory rats were collected on days 3, 7, 14, 21 and 30 after the operation. Plasma urea, creatinine, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and lactate dehydrogenase levels were measured. Results. No clinically significant changes in concentrations of low molecular weight metabolites of nitrogen metabolism or liver enzymes activity, alkaline phosphatase and lactate dehydrogenase activity were observed after implantation of a biological vascular graft from bovine xenopericardium compared to the animals with implanted synthetic vascular graft. Conclusion. The use of a biological vascular graft made from bovine xenopericardium does not cause clinically significant changes in blood biochemical parameters in laboratory rats.

Characteristics and Outcome of Vascular Graft Infections: A Risk Factor and Survival Analysis.

Vascular graft infection (VGI) is a serious complication after implantation of arterial vascular grafts. Optimal surgical and pathogen-specific antimicrobial treatment regimens for VGI are largely unknown. We evaluated patients with arterial VGI according to onset, location, microbiological and imaging characteristics, and surgical and antimicrobial treatment and performed an outcome evaluation. Consecutive patients with VGI treated in 2 hospitals from 2010 through 2020 were retrospectively analyzed. Uniform definition criteria and standardized outcome evaluation were applied. Logistic regression was used for multiple analysis; survival analysis was performed with Kaplan-Meier analysis and a log-rank test. Seventy-eight patients with VGI were included: 30 early-onset cases (<8 weeks after graft implantation) and 48 late-onset cases, involving 49 aortic and 29 peripheral grafts. The median time from initial implantation to diagnosis of VGI was significantly longer in aortic than peripheral VGIs (363 vs 56 days, P = .018). Late-onset VGI (odds ratio [OR], 7.3; P = .005) and the presence of surgical site infection/complication (OR, 8.21; P = .006) were independent risk factors for treatment failure. Surgical site infection/complication was associated with a higher risk for early-onset VGI (OR, 3.13; P = .040). Longer infection-free survival was observed in cases where the infected graft was surgically removed (P = .037). This study underlines the importance of timely diagnosis of VGI and preventing surgical site infections/complications at graft implantation. It highlights the complexity of infection eradication, especially for late-onset infections, and the importance of adequate antimicrobial and surgical treatment.

Preliminary in-silico analysis of vascular graft implantation configuration and surface modification

Vascular grafts are used to reconstruct congenital cardiac anomalies, redirect flow, and offer vascular access. Donor tissue, synthetic, or more recently tissue-engineered vascular grafts each carry limitations spanning compatibility, availability, durability and cost. Synthetic and tissue-engineered grafts offer the advantage of design optimization using in-silico or in-vitro modeling techniques. We focus on an in-silico parametric study to evaluate implantation configuration alternatives and surface finishing impact of a novel silicon-lined vascular graft. The model consists of a synthetic 3D-generic model of a graft connecting the internal carotid artery to the jugular vein. The flow is assumed unsteady, incompressible, and blood is modeled as a non-Newtonian fluid. A comparison of detached eddy turbulence and laminar modeling to determine the required accuracy needed found mild differences mainly dictated by the roughness level. The conduit walls are modeled as non-compliant and fixed. The shunt configurations considered, are straight and curved with varied surface roughness. Following a grid convergence study, two shunt configurations are analyzed to better understand flow distribution, peak shear locations, stagnation regions and eddy formation. The curved shunt was found to have lower peak and mean wall-shear stress, while resulting in lower flow power system and decreased power loss across the graft. The curved smooth surface shunt shows lower peak and mean wall-shear stress and lower power loss when compared to the straight shunt.

P34: Polymers With Antimicrobial Properties For Manufacture Of Tissue-Engineered Vascular Grafts To Prevent Infection.

After vascular graft implantation, the most dreaded complication is a bacterial infection due to high morbidity (45%) and mortality rates (30%). The treatment is challenging due to the possibility of encountering antibiotic-resistant strains and the inability of drugs to penetrate the formed biofilms, which can be manifested even years after implantation. Polymer-based tissue-engineered vascular grafts (TEVGs) with antimicrobial properties might be a strategy to prevent infection. Polycaprolactone (PCL) was chemically oxidized to introduce carboxyl groups on the polymer backbone (PCL-COOH) and then in-situ functionalized with Polyethylene Glycol (PEG 4-Arm-NH2) and Buforin II (PPB). In parallel, magnetite-silver core-shell nanoparticles were synthesized and dispersed in a PCL/gelatin blend (75:25) (PGN). Solvent casting was then allowed for both polymers and functionalization was confirmed via Fourier-transformed infrared spectroscopy (FTIR) and Thermogravimetric analysis (TGA). Metabolic activity (MTT) and hemolysis assays were performed to validate biocompatibility. Antimicrobial tests were conducted by a disc diffusion assay and a leachate toxicity assay using S.aureus and E.coli cultures. Physicochemical characterization showed effective polymer functionalization with PPB, as well as homogeneous nanoparticle incorporation in the PGN blend. Antimicrobial activity against S.aureus and E.coli was found for both polymers along with high cell viability (> 80%) and low hemolytic behavior (<5%), indicating high biocompatibility and hemocompatibility. The strategy proposed here holds much promise for long-term infection control as PCL is the most frequently used polymer for TEVGs fabrication.

Vascular endothelial growth factor attenuates neointimal hyperplasia of decellularized small-diameter vascular grafts by modulating the local inflammatory response.

Small-diameter vascular grafts (diameter <6mm) are in high demand in clinical practice. Neointimal hyperplasia, a common complication after implantation of small-diameter vascular grafts, is one of the common causes of graft failure. Modulation of local inflammatory responses is a promising strategy to attenuates neointimal hyperplasia. Vascular endothelial growth factor (VEGF) is an angiogenesis stimulator that also induces macrophage polarization and modulates inflammatory responses. In the present study, we evaluated the effect of VEGF on the neointima hyperplasia and local inflammatory responses of decellularized vascular grafts. In the presence of rhVEGF-165 in RAW264.6 macrophage culture, rhVEGF-165 induces RAW264.6 macrophage polarization to M2 phenotype. Decellularized bovine internal mammary arteries were implanted into the subcutaneous and infrarenal abdominal aorta of New Zealand rabbits, with rhVEGF-165 applied locally to the adventitial of the grafts. The vascular grafts were removed en-bloc and submitted to histological and immunofluorescence analyses on days 7 and 28 following implantation. The thickness of the fibrous capsule and neointima was thinner in the VEGF group than that in the control group. In the immunofluorescence analysis, the number of M2 macrophages and the ratio of M2/M1 macrophages in vascular grafts in the VEGF group were higher than those in the control group, and the proinflammatory factor IL-1 was expressed less than in the control group, but the anti-inflammatory factor IL-10 was expressed more. In conclusion, local VEGF administration attenuates neointimal hyperplasia in decellularized small-diameter vascular grafts by inducing macrophage M2 polarization and modulating the inflammatory response.

Integral and Local Methods for the Evaluation of the Hemostasiological Profile in Sheep at Various Stages of Implantation of a Biodegradable Vascular Graft.

The object of the study was the whole blood of sheep collected at the stage of premedication, during the intraoperative period, and in the early postoperative period. Thromboelastography was used to assess the kinetics of clot formation and changes in its viscoelastic properties in whole blood samples. The thrombin generation test was performed in platelet-rich plasma (PRP) and platelet-poor plasma (PPP) with the assessment of quantitative and temporal parameters. The platelet factor 4 concentration in PRP and PPP was measured by the enzyme immunoassay. The functional activity of platelets in PPP was assessed with inductors and without additional stimulation. Prothrombin complex activity, APTT values, thrombin time, fibrinogen concentration, antithrombin III and protein C activity, soluble fibrin monomer complexes, and fibrinolysis were determined in blood plasma. Multidirectional changes in the hemostasiological profile at various stages of vascular prosthesis implantation have been revealed. On the one hand, it is an increased prothrombogenic status, on the other hand, it is the development of hypocoagulation. Shortening of the R (blood coagulation time) and K (clot formation time) intervals and an increase in the angle parameter and maximum amplitude on the thromboelastogram in all the studied periods relative to the reference values, a significant increase in platelet factor 4 in PRP and increased platelet aggregation testified in favor of hypercoagulation. However, the quantitative parameters of the thrombin generation test and a number of coagulogram indicators pointed to hypocoagulation in the intraoperative and early postoperative periods. The comparative analysis of local tests characterizing the state of hemostasis and indicators of integral methods demonstrated the advantages of the latter in assessing thrombotic risks during implantation of vascular grafts. Local tests are not sufficient to assess the dynamics of the coagulation process in real time and are not always sensitive to hypercoagulation. The use of integral methods will help to fill these gaps, make a timely diagnosis of hypercoagulability and minimize the risks associated with the implantation of vascular grafts in future.

The use of antimicrobial biomaterials as a savior from post-operative vascular graft-related infections: A review

Cardiovascular diseases rank first in mortality and morbidity. There are various treatments for replacing a blood vessel artificially, such as autologous graft implantation, bio-engineered vascular graft implantation, etc. Due to the external medical intervention or immunocompromised state in the patients, there are high chances of septic infection at the site of implantation. This increases the risk of blood-related infections in these patients. Thus, it is imperative to avoid the spread of infection and to destroy the infection-causing microorganisms by incorporating an antimicrobial agent in the implantable biomaterial. For instance, use combination of minocycline, chlorhexidine, and rifampin was impregnated on Dacron, and PTFE (polytetrafluoroethylene) vascular grafts showed a 100% patency rate and increased antibiotic activity than the counterparts. This review summarises various methods of incorporating antimicrobial agents in the biomaterial for developing an antimicrobial vascular graft.

Location matters: Offset in tissue-engineered vascular graft implantation location affects wall shear stress in porcine models

ObjectiveAlthough surgical simulation using computational fluid dynamics has advanced, little is known about the accuracy of cardiac surgical procedures after patient-specific design. We evaluated the effects of discrepancies in location for patient-specific simulation and actual implantation on hemodynamic performance of patient-specific tissue-engineered vascular grafts (TEVGs) in porcine models. MethodsMagnetic resonance angiography and 4-dimensional (4D) flow data were acquired in porcine models (n = 11) to create individualized TEVGs. Graft shapes were optimized and manufactured by electrospinning bioresorbable material onto a metal mandrel. TEVGs were implanted 1 or 3 months postimaging, and postoperative magnetic resonance angiography and 4D flow data were obtained and segmented. Displacement between intended and observed TEVG position was determined through center of mass analysis. Hemodynamic data were obtained from 4D flow analysis. Displacement and hemodynamic data were compared using linear regression. ResultsPatient-specific TEVGs were displaced between 1 and 8 mm during implantation compared with their surgically simulated, intended locations. Greater offset between intended and observed position correlated with greater wall shear stress (WSS) in postoperative vasculature (P < .01). Grafts that were implanted closer to their intended locations showed decreased WSS. ConclusionsPatient-specific TEVGs are designed for precise locations to help optimize hemodynamic performance. However, if TEVGs were implanted far from their intended location, worse WSS was observed. This underscores the importance of not only patient-specific design but also precision-guided implantation to optimize hemodynamics in cardiac surgery and increase reproducibility of surgical simulation.

Does a small-diameter rod-type tunneler reduce postoperative swelling? An evaluation using a canine arteriovenous graft model.

Sheath-type tunnelers are frequently used to create vascular access using vascular grafts. However, during vascular access creation, tunnelers damage the surrounding tissues, consequently causing problems, such as swelling, failure to heal, and infection. This study evaluated a novel rod-type tunneler that was designed to prevent tunneler-related tissue damage and its sequelae. We developed a small-diameter rod-type tunneler that reduces injuries during subcutaneous tunnel creation. The rod diameter of this tunneler is smaller than the vascular graft diameter being implanted. It has a structure in which a vascular graft is implanted at a target site by grasping and pulling the vascular graft. Three dogs were used in the experiment, and arteriovenous grafts were created using a rod-type and a sheath-type tunneler on the left and right thighs, respectively, with a different type of commercially available graft used in each dog. The edema of the tissues surrounding the vascular graft was measured at 11 sites by ultrasonography at prespecified intervals. Compared with implantation using a sheath-type tunneler, when the self-sealing Rapidax II was implanted using the small-diameter rod-type tunneler, the postimplantation edema (degree of change) decreased by 28-53% and 80-247% in the peri-vascular-graft area and within the loop, respectively. The MAXIFLO and SEALPTFE did not significantly reduce postoperative edema but exhibited a tendency for improved postimplantation tissue healing. The reduced-diameter rod-type tunneler may be a useful device for vascular graft implantation.

Mechanisms of Calcification in Materials for Valvular and Vascular In Situ Tissue Engineering

Objective: In situ tissue engineering (TE) of vascular and valvular graft implants has rapidly progressed over the past two decades as it prospects a great alternative to autologous, xenografted, and non-biological materials for vessel and valve replacements. In this approach, a synthetic degradable valve or vessel replacement is implanted at the site of a diseased valve or vessel, where it gradually remodels into viable tissue.1 However promising, some possible challenges need to be assessed to ensure safe clinical translation of this technique.

Vascular Imaging in Small Animals Using Clinical Ultrasound Scanners.

Conventional ultrasound with frequency (2-15MHz) has been a global diagnostic and therapeutic tool in clinical medicine, and high-frequency ultrasound (>30MHz) has been a powerful investigative device for preclinical studies such as cardiovascular research. In this chapter, we describe the use of conventional ultrasound with a 2.5-10MHz transducer as an investigative device for the measurement/detection of blood flow in rabbit model. The chapter will describe the procedures for the preparation of sonographer, imaging locations, and the details of the rabbits used as well as detailed imaging steps for the preoperative, immediately after operation, and postoperative follow-up ultrasound for vascular surgery, using a vascular graft implantation as an example. We also provide useful notes to avoid pitfalls for successful imaging. The overall goal of this chapter is to deliver the steps in using low-cost, non-invasive, and highly versatile clinical ultrasound imaging in preclinical small animal testing.

Rabbit Surgery Protocol for End-to-End and End-to-Side Vascular Graft Anastomosis.

Preclinical testing in animal model is a required stage of vascular device development. Among small animal models, rabbits provide vasculature with relative larger caliber for anastomotic implantation of vascular grafts as preclinical testing before conducting large animal studies. Rabbits have similar hemostatic mechanism with human and can accommodate vascular grafts with various diameters at different locations, and thus provide a valid model to assess small-diameter vascular grafts. This chapter will describe the procedures and materials required to conduct survival surgery in rabbit carotid artery models for implantation of small-diameter tubular grafts with an end-to-side and end-to-end anastomotic technique.

In vivo recellularization of xenogeneic vascular grafts decellularized with high hydrostatic pressure method in a porcine carotid arterial interpose model.

Autologous vascular grafts are widely used in revascularization surgeries for small caliber targets. However, the availability of autologous conduits might be limited due to prior surgeries or the quality of vessels. Xenogeneic decellularized vascular grafts from animals can potentially be a substitute of autologous vascular grafts. Decellularization with high hydrostatic pressure (HHP) is reported to highly preserve extracellular matrix (ECM), creating feasible conditions for recellularization and vascular remodeling after implantation. In the present study, we conducted xenogeneic implantation of HHP-decellularized bovine vascular grafts from dorsalis pedis arteries to porcine carotid arteries and posteriorly evaluated graft patency, ECM preservation and recellularization. Avoiding damage of the luminal surface of the grafts from drying significantly during the surgical procedure increased the graft patency at 4 weeks after implantation (P = 0.0079). After the technical improvement, all grafts (N = 5) were patent with mild stenosis due to intimal hyperplasia at 4 weeks after implantation. Neither aneurysmal change nor massive thrombosis was observed, even without administration of anticoagulants nor anti-platelet agents. Elastica van Gieson and Sirius-red stainings revealed fair preservation of ECM proteins including elastin and collagen after implantation. The luminal surface of the grafts were thoroughly covered with von Willebrand factor-positive endothelium. Scanning electron microscopy of the luminal surface of implanted grafts exhibited a cobblestone-like endothelial cell layer which is similar to native vascular endothelium. Recellularization of the tunica media with alpha-smooth muscle actin-positive smooth muscle cells was partly observed. Thus, we confirmed that HHP-decellularized grafts are feasible for xenogeneic implantation accompanied by recellularization by recipient cells.

The Influence of a Knitted Hydrophilic Prosthesis of Blood Vessels on the Activation of Coagulation System—In Vitro Study

The replacement of affected blood vessels of the polymer material can cause imbalances in the blood haemostatic system. Changes in blood after the implantation of vascular grafts depend not only on the chemical composition but also on the degree of surface wettability. The Dallon® H unsealed hydrophilic knitted vascular prosthesis double velour was assessed at work and compare with hydrophobic vascular prosthesis Dallon®. Spectrophotometric studies were performed in the infrared and differential scanning calorimetry, which confirmed the effectiveness of the process of modifying vascular prostheses. Determination of the parameters of coagulation time of blood after contact in vitro with Dallon® H vascular prosthesis was also carried out. Prolongation of activated thromboplastin time, decreased activity of factor XII, IX and VIII, were observed. The prolonged thrombin and fibrinogen were reduced in the initial period of the experiment. The activity of plasminogen and antithrombin III and protein C were at the level of control value. The observed changes in the values of determined parameters blood coagulation do not exceed the range of referential values for those indexes. The observed changes are the result of considerable blood absorptiveness by the prosthesis of blood vessels and their sealing.

Long-term clinical outcomes of losartan in patients with Marfan syndrome: follow-up of the multicentre randomized controlled COMPARE trial.

AimsThe COMPARE trial showed a small but significant beneficial effect of 3-year losartan treatment on aortic root dilatation rate in adults with Marfan syndrome (MFS). However, no significant effect was found on clinical endpoints, possibly due to a short follow-up period. The aim of the current study was therefore to investigate the long-term clinical outcomes after losartan treatment.Methods and resultsIn the original COMPARE study (inclusion 2008–2009), adult patients with MFS (n = 233) were randomly allocated to either the angiotensin-II receptor blocker losartan® on top of regular treatment (β-blockers in 71% of the patients) or no additional medication. After the COMPARE trial period of 3 years, study subjects chose to continue their losartan medication or not. In a median follow-up period of 8 years, 75 patients continued losartan medication, whereas 78 patients, originally allocated to the control group, never used losartan after inclusion. No differences existed between baseline characteristics of the two groups except for age at inclusion [losartan 34 (interquartile range, IQR 26–43) years, control 41 (IQR 30–52) years; P = 0.031], and β-blocker use (losartan 81%, control 64%; P = 0.022). A pathological FBN1 mutation was present in 76% of patients and 58% of the patients were male. Clinical endpoints, defined as all-cause mortality, aortic dissection/rupture, elective aortic root replacement, reoperation, and vascular graft implantation beyond the aortic root, were compared between the two groups. A per-patient composite endpoint was also analysed. Five deaths, 14 aortic dissections, 23 aortic root replacements, 3 reoperations, and 3 vascular graft implantations beyond the aortic root occurred during follow-up. Except for aortic root replacement, all endpoints occurred in patients with an operated aortic root. Patients who used losartan during the entire follow-up period showed a reduced number of events compared to the control group (death: 0 vs. 5, P = 0.014; aortic dissection: 3 vs. 11, P = 0.013; elective aortic root replacement: 10 vs. 13, P = 0.264; reoperation: 1 vs. 2, P = 0.463; vascular graft implantations beyond the aortic root 0 vs. 3, P = 0.071; and composite endpoint: 14 vs. 26, P = 0.019). These results remained similar when corrected for age and β-blocker use in a multivariate analysis.ConclusionThese results suggest a clinical benefit of combined losartan and β-blocker treatment in patients with MFS.

A Brief Report on an Implantation of Small-Caliber Biodegradable Vascular Grafts in a Carotid Artery of the Sheep.

The development of novel biodegradable vascular grafts of a small diameter (<6 mm) is an unmet clinical need for patients requiring arterial replacement. Here we performed a pre-clinical study of new small-caliber biodegradable vascular grafts using a sheep model of carotid artery implantation. The 4 mm diameter vascular grafts were manufactured using a mix of polyhydroxybutyrate/valerate and polycaprolactone supplemented with growth factors VEGF, bFGF and SDF-1α (PHBV/PCL-GFmix) and additionally modified by a polymer hydrogel coating with incorporation of drugs heparin and iloprost (PHBV/PCL-GFmixHep/Ilo). Animals with carotid artery autograft implantation and those implanted with clinically used GORE-TEX® grafts were used as control groups. We observed that 24 h following surgery, animals with carotid artery autograft implantation showed 87.5% patency, while all the PHBV/PCL-GFmix and GORE-TEX® grafts displayed thrombosis. PHBV/PCL-GFmixHep/Ilo grafts demonstrated 62.5% patency 24 h following surgery and it had remained at 50% 1 year post-operation. All the PHBV/PCL grafts completely degraded less than 1 year following surgery and were replaced by de novo vasculature without evidence of calcification. On the other hand, GORE-TEX® grafts displayed substantial amounts of calcium deposits throughout graft tissues. Thus, here we report a potential clinical usefulness of PHBV/PCL grafts upon their additional modification by growth factors and drugs to promote endothelialization and reduce thrombogenicity.

Aptamer supported in vitro endothelialization of poly(ether imide) films.

Implantation of synthetic small-diameter vascular bypass grafts is often associated with an increased risk of failure, due to thrombotic events or late intimal hyperplasia. As one of the causes an insufficient hemocompatibility of the artificial surface is discussed. Endothelialization of synthetic grafts is reported to be a promising strategy for creating a self-renewing and regulative anti-thrombotic graft surface. However, the establishment of a shear resistant cell monolayer is still challenging. In our study, cyto- and immuno-compatible poly(ether imide) (PEI) films were explored as potential biomaterial for cardiovascular applications. Recently, we reported that the initial adherence of primary human umbilical vein endothelial cells (HUVEC) was delayed on PEI-films and about 9 days were needed to establish a confluent and almost shear resistant HUVEC monolayer. To accelerate the initial adherence of HUVEC, the PEI-film surface was functionalized with an aptamer-cRGD peptide based endothelialization supporting system. With this functionalization the initial adherence as well as the shear resistance of HUVEC on PEI-films was considerable improved compared to the unmodified polymer surface. The in vitro results confirm the general applicability of aptamers for an efficient functionalization of substrate surfaces.

BIODEGRADABLE VASCULAR GRAFT MODIFIED BY RGD-PEPTIDES: EXPERIMENTAL RESEARCH

Research goals. To study the effectiveness of RGD-peptide modification of the small-diameter biodegradable vascular grafts depending on the type of a linker and RGD configuration.Material and Methods. Tubular scaffolds with a diameter of 1.5 and 4.0 mm were produced by electrospinning from polyhydroxybutyrate/valerate (PHBV) and polycaprolactone (PCL). The PHBV/PCL grafts were modified with RGD peptides. In vitro experiments showed the degree of erythrocyte hemolysis and adhesion of the platelets and endothelial cells when in contact with a modified surface. The physico-mechanical properties and the structure of graft surface were studied before and after modification. The PHBV/PCL and PHBV/PCL/RGD vascular grafts were implanted into the abdominal aorta of rats for the periods of 1 and 3 months. Explant samples were studied using confocal microscopy and histological methods.Results. The results of physical and mechanical tests showed a significant decrease in the strength properties of the PHBV/PCL/RGD grafts relative to the unmodified analogs. A significant increase in platelet aggregation was found in the modified grafts. The level of adhesion of the endothelial cells on the modified surfaces was higher than that on the unmodified surfaces. Shortterm implantation of the grafts for 1 and 3 months showed that the modified grafts had higher patency and a less tendency to calcification compared with the unmodified grafts. Immunofluorescence study demonstrated the significant superiority of the modified vascular grafts in terms of stimulating the formation of a mature endothelial monolayer. A longer linker of 4,7,10-trioxa-1,13-tridecane diamine was found to increase the bioavailability of RGD peptides; the use of RGDK and c[RGDFK] for surface modification of the grafts stimulated early endothelialization of the internal surface of the implants and reduced the prosthetic wall calcification tendency, which together increased the patency of the implanted grafts.Conclusion. In short-term implantation of biodegradable vascular grafts modified with RGD peptides, the grafts with RGDK and c[RGDFK], attached to the surface of the prostheses through the 4,7,10-triox-1,13-tridecane diamine linker, showed the best results in terms of endothelial adhesion and maintenance of the viability of the endothelial cells in vitro and endothelialization in vivo; these grafts had high patency after implantation into the bloodstream of small laboratory animals and a less tendency to calcification.