Biocompatibility of Small-Diameter Vascular Grafts in Different Modes of RGD Modification

Антонова, Л. В.; Silnikov, Vladimir N.; Sevost'yanova, V. V.; Yuzhalin, Arseniy E.; Королева, Л. С.; Великанова, Е. А.; Миронов, А. В.; Godovikova, Tatyana S.; Kutikhin, Anton G.; Глушкова, Т. В.; Serpokrylova, Inna Yu.; Senokosova, E. A.; Матвеева, В. Г.; Khanova, Mariam Yu.; Akentyeva, T.N.; Кривкина, Е. О.; Kudryavtseva, Yu. А.; Ls, Barbarash

doi:10.3390/polym11010174

Cited by 26 publications

(24 citation statements)

References 31 publications

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“…Previous studies also reported that these combinations improved adhesion, viability, and proliferation of both endothelial colony-forming cells and human umbilical vein endothelial cells on the surface of electrospun PHBV/PCL scaffolds. 25 , 26 Thus, we tested the performance of TTDDA/RGDK-, TTDDA/AhRGD-, and TTDDA/c[RGDFK]-modified patches upon the implantation into the rat abdominal aorta. Unmodified PHBV/PCL patches and commercially available KemPeriplas-Neo patches were used as controls.…”

Section: Resultsmentioning

confidence: 99%

Biodegradable Patches for Arterial Reconstruction Modified with RGD Peptides: Results of an Experimental Study

et al. 2020

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Modification by Arg-Gly-Asp (RGD) peptides is a promising approach to improve the biocompatibility of biodegradable vascular patches for arteriotomy. In this study, we evaluated the performance of vascular patches electrospun using a blend of polycaprolactone (PCL) and polyhydroxybutyrate/valerate (PHBV) and additionally modified with RGDK, AhRGD, and c[RGDFK] peptides using 1,6-hexamethylenediamine or 4,7,10-trioxa-1,13-tridecanediamine (TTDDA) linkers. We examined mechanical properties and hemocompatibility of resulting patches before implanting them in rat abdominal aortas to assess their performance in vivo. Patches were explanted 1, 3, 6, and 12 months postoperation followed by histological and immunofluorescence analyses. Patches manufactured from the human internal mammary artery or commercially available KemPeriplas-Neo xenopericardial patches were used as a control. The tensile strength and F max of KemPeriplas-Neo patches were 4- and 16.7-times higher than those made of human internal mammary artery, respectively. Both RGD-modified and unmodified PHBV/PCL patches demonstrated properties similar to a human internal mammary artery patch. Regardless of RGD modification, experimental PHBV/PCL patches displayed fewer lysed red blood cells and resulted in milder platelet aggregation than KemPeriplas-Neo patches. Xenopericardial patches failed to form an endothelial layer in vivo and were prone to calcification. By contrast, TTDDA/RGDK-modified biodegradable patches demonstrated a resistance to calcification. Modification by TTDDA/RGDK and TTDDA/c[RGDFK] facilitated the formation of neovasculature upon the implantation in vivo.

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Section: Resultsmentioning

confidence: 99%

Biodegradable Patches for Arterial Reconstruction Modified with RGD Peptides: Results of an Experimental Study

et al. 2020

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“…Также удалось добиться более качественного эндотелиального монослоя на внутренней поверхности графтов, имплантированных лабораторным крысам, и 100% проходимости графтов на разных сроках имплантации (1 и 3 месяца). Одновременно гемосовместимые свойства такого материала были выше в сравнении с образцами, модифицированными тем же циклическим RGD-пептидом, но сшитым с полимерной поверхностью через короткий линкер -1,6-hexamethylenediamine [100].…”

Section: виды конфигураций Rgd и сопряженные с ними лиганды/линкерыunclassified

Biodegradable small-diameter vascular graft: types of modification with bioactive molecules and RGD peptides

Senokosova

Кривкина

Антонова

et al. 2020

RJTAO

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The need for small-diameter grafts for replacing the damaged area of the blood pool is still very high. These grafts are very popular for coronary artery bypass grafting. Polymeric synthetic grafts are an alternative to autografts. A promising area of tissue engineering is the creation of a biodegradable graft. It can serve as the basis for de novo generation of vascular tissue directly in the patient’s body. Optimization of the polymer composition of products has led to improved physicomechanical and biocompatible properties of the products. However, the improvements are still far from needed. One of the decisive factors in the reliability of a small-diameter vascular graft is the early formation of endothelial lining on its inner surface, which can provide atrombogenic effect and full lumen of the future newly formed vessel. To achieve this goal, grafts are modified by incorporating bioactive molecules or functionally active peptide sequences into the polymer composition or immobilizing on its inner surface. Peptide sequences include cell adhesion site – arginine-glycine-aspartic acid (RGD peptide). This sequence is present in most extracellular matrix proteins and has a tropism for integrin receptors of endothelial cells. Many studies have shown that imitation of the functional activity of the natural extracellular matrix can promote spontaneous endothelization of the inner surface of a vascular graft. Moreover, configuration of the RGD peptide determines the survival and differentiation of endothelial cells. The linker through which the peptide is crosslinked to the polymer surface determines the bioavailability of the RGD peptide for endothelial cells.

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“…To modify the surfaces of 1.5 mm tubular PHBV/PCL polymer matrices, hexamethylenediamine, glutaraldehyde, ninhydrin, ascorbic acid (Sigma-Aldrich, USA), and RGD (NanoTech-S, Russia) have been used. First, matrices were treated with 10% solution of hexamethylenediamine in the mixture of isopropanol and water (1:1) at 37°С for 30 min with a 2-fold reduction of modification time [14,15]. Each graft here and further was in a separate 15 ml reactor in the horizontal position with constant swinging.…”

Section: Fabrication Of Tubular Phbv/pcl Scaffoldsmentioning

confidence: 99%

“…The maximal density of graft surface modification during 60 min was 8.9 nM/cm 2 [14]. However, the physical and mechanical characteristics of the grafts have become much worse [15].…”

Section: Introductionmentioning

confidence: 99%

Novel Technology of Modifying the Surface of Biodegradable Vascular Grafts with RGD Peptides: Effect on the Surface Structure and Physical and Mechanical Properties

Антонова¹,

Silnikov²,

Глушкова³

et al. 2019

Sovrem Tehnol Med

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The aim of the study was to assess the effectiveness of a new technology of modifying biodegradable small-diameter vascular grafts from polyhydroxybutyrate/valerate (PHBV) and polycaprolactone (PCL) with RGD peptides and its effect on the surface structure and physical and mechanical characteristics of these grafts. Materials and Methods. Tubular polymer prostheses (matrices, grafts) 1.5 mm in diameter were fabricated using electrospinning method from the composition of PHBV and PCL polymers. Hexamethylendiamine, glutaraldehyde, ascorbic acid, and arginine-glycineaspartic acid were used to modify the surface of polymer scaffolds. The quality of the modification performed was assessed using a ninhydrin test and by determining the arginine-containing peptide. The structure of the graft surfaces before and after modification was examined using scanning electron microscopy. Mechanical properties were evaluated by uniaxial tension with determination of ultimate tensile strength, relative elongation, and Young's modulus. The characteristics of the internal mammary artery (a. mammaria interna) were used as a control of these parameters, vascular synthetic ePTFE-based linear grafts served as a group of comparison. Results. Presence of RGD peptides on the polymer surface was confirmed by a Sakaguchi test which is specific for arginine. The mode of modification did not alter the surface structure of the polymer grafts but resulted in the reduction of their rigidity by 1.6 times, strength by 3.9 times, and relative elongation by 1.7 times. The physical and mechanical properties of PHBV/PCL+RGD grafts approached those of the a. mammaria. Conclusion. The developed technology of modifying the surfaces of PHBV/PCL-based vascular grafts with RGD peptides made it possible to obtain PHBV/PCL+RGD grafts with the physical and mechanical properties approaching to those of the native vessels without any changes of the surface structure.

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Biocompatibility of Small-Diameter Vascular Grafts in Different Modes of RGD Modification

Cited by 26 publications

References 31 publications

Biodegradable Patches for Arterial Reconstruction Modified with RGD Peptides: Results of an Experimental Study

Biodegradable Patches for Arterial Reconstruction Modified with RGD Peptides: Results of an Experimental Study

Biodegradable small-diameter vascular graft: types of modification with bioactive molecules and RGD peptides

Novel Technology of Modifying the Surface of Biodegradable Vascular Grafts with RGD Peptides: Effect on the Surface Structure and Physical and Mechanical Properties

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