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

Viktoriia V Sevostianova; Larisa V Antonova; Andrey V Mironov; Arseniy E Yuzhalin; Vladimir N Silnikov; Tatiana V Glushkova; Tatyana S Godovikova; Evgeniya O Krivkina; Evgeniy Bolbasov; Tatiana N Akentyeva; Mariam Yu Khanova; Vera G Matveeva; Elena A Velikanova; Roman S Tarasov; Leonid S Barbarash

doi:10.1021/acsomega.0c02593

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

ACS Omega. 2020 Aug 19;5(34):21700-21711. doi: 10.1021/acsomega.0c02593. eCollection 2020 Sep 1.

Authors

Viktoriia V Sevostianova¹, Larisa V Antonova¹, Andrey V Mironov¹, Arseniy E Yuzhalin¹, Vladimir N Silnikov², Tatiana V Glushkova¹, Tatyana S Godovikova², Evgeniya O Krivkina¹, Evgeniy Bolbasov³, Tatiana N Akentyeva¹, Mariam Yu Khanova¹, Vera G Matveeva¹, Elena A Velikanova¹, Roman S Tarasov¹, Leonid S Barbarash¹

Affiliations

¹ Research Institute for Complex Issues of Cardiovascular Diseases, Kemerovo 650002, Russia.
² Institute of Chemical Biology and Fundamental Medicine of the Siberian Branch of the Russian Academy of Sciences, Novosibirsk 630090, Russia.
³ National Research Tomsk Polytechnic University, Tomsk 634050, Russia.

Abstract

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.