Sevostianova Viktoriia V, Antonova Larisa V, Mironov Andrey V, Yuzhalin Arseniy E, Silnikov Vladimir N, Glushkova Tatiana V, Godovikova Tatyana S, Krivkina Evgeniya O, Bolbasov Evgeniy, Akentyeva Tatiana N, Khanova Mariam Yu, Matveeva Vera G, Velikanova Elena A, Tarasov Roman S, Barbarash Leonid S
Research Institute for Complex Issues of Cardiovascular Diseases, Kemerovo 650002, Russia.
Institute of Chemical Biology and Fundamental Medicine of the Siberian Branch of the Russian Academy of Sciences, Novosibirsk 630090, Russia.
ACS Omega. 2020 Aug 19;5(34):21700-21711. doi: 10.1021/acsomega.0c02593. eCollection 2020 Sep 1.
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 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.
用精氨酸 - 甘氨酸 - 天冬氨酸（RGD）肽进行修饰是一种很有前景的方法，可用于改善用于动脉切开术的可生物降解血管补片的生物相容性。在本研究中，我们评估了使用聚己内酯（PCL）和聚羟基丁酸酯/戊酸酯（PHBV）的混合物进行电纺丝，并使用1,6 - 己二胺或4,7,10 - 三氧杂 - 1,13 - 十三烷二胺（TTDDA）接头用RGDK、AhRGD和c[RGDFK]肽进行额外修饰的血管补片的性能。在将所得补片植入大鼠腹主动脉之前，我们检查了其力学性能和血液相容性，以评估它们在体内的性能。术后1、3、6和12个月取出补片，随后进行组织学和免疫荧光分析。用人乳内动脉制成的补片或市售的KemPeriplas - Neo异种心包补片用作对照。KemPeriplas - Neo补片的拉伸强度和 分别是人乳内动脉制成的补片的4倍和16.7倍。RGD修饰和未修饰的PHBV/PCL补片均表现出与人乳内动脉补片相似的性能。无论是否进行RGD修饰，实验性PHBV/PCL补片裂解的红细胞数量均较少，且血小板聚集程度比KemPeriplas - Neo补片更轻。异种心包补片在体内未能形成内皮层，且易于钙化。相比之下，TTDDA/RGDK修饰的可生物降解补片表现出抗钙化能力。TTDDA/RGDK和TTDDA/c[RGDFK]修饰促进了体内植入后新生血管的形成。
