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

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-glycine-aspartic 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.

1. Fadini G.P., Rattazzi M., Matsumoto T., Asahara T., Khosla S. Emerging role of circulating calcifying cells in the bone-vascular axis. Circulation 2012; 125(22): 2772–2781, https://doi.org/10.1161/circulationaha.112.090860.
2. Lee K.-W., Johnson N.R., Gao J., Wang Y. Human progenitor cell recruitment via SDF-1α coacervate-laden PGS vascular grafts. Biomaterials 2013; 34(38): 9877–9885, https://doi.org/10.1016/j.biomaterials.2013.08.082.
3. Ren X., Feng Y., Guo J., Wang H., Li Q., Yang J., Hao X., Lv J., Ma N., Li W. Surface modification and endothelialization of biomaterials as potential scaffolds for vascular tissue engineering applications. Chem Soc Rev 2015; 44(15): 5680–5742, https://doi.org/10.1039/c4cs00483c.
4. Wang F., Li Y., Shen Y., Wang A., Wang S., Xie T. The functions and applications of RGD in tumor therapy and tissue engineering. Int J Mol Sci 2013; 14(7): 13447–13462, https://doi.org/10.3390/ijms140713447.
5. Harburger D.S., Calderwood D.A. Integrin signalling at a glance. J Cell Sci 2008; 122(2): 159–163, https://doi.org/10.1242/jcs.018093.
6. Tiwari A., Kidane A., Salacinski H., Punshon G., Hamilton G., Seifalian A.M. Improving endothelial cell retention for single stage seeding of prosthetic grafts: use of polymer sequences of arginine-glycine-aspartate. Eur J Vasc Endovasc Surg 2003; 25(4): 325–329, https://doi.org/10.1053/ejvs.2002.1854.
7. Kidane A.G., Punshon G., Salacinski H.J., Ramesh B., Dooley A., Olbrich M., Heitz J., Hamilton G., Seifalian A.M. Incorporation of a lauric acid-conjugated GRGDS peptide directly into the matrix of a poly(carbonate-urea)urethane polymer for use in cardiovascular bypass graft applications. J Biomed Mater Res A 2006; 79(3): 606–617, https://doi.org/10.1002/jbm.a.30817.
8. Alobaid N., Salacinski H.J., Sales K.M., Ramesh B., Kannan R.Y., Hamilton G., Seifalian A.M. Nanocomposite containing bioactive peptides promote endothelialisation by circulating progenitor cells: an in vitro evaluation. Eur J Vasc Endovasc Surg 2006; 32(1): 76–83, https://doi.org/10.1016/j.ejvs.2005.11.034.
9. Salacinski H.J., Hamilton G., Seifalian A.M. Surface functionalization and grafting of heparin and/or RGD by an aqueous-based process to a poly(carbonate-urea)urethane cardiovascular graft for cellular engineering applications. J Biomed Mater Res A 2003; 66(3): 688–697, https://doi.org/10.1002/jbm.a.10020.
10. Gabriel M., van Nieuw Amerongen G.P., van Hinsbergh V.W.M., van Nieuw Amerongen A.V., Zentner A. Direct grafting of RGD-motif-containing peptide on the surface of polycaprolactone films. J Biomater Sci Polym Ed 2006; 17(5): 567–577, https://doi.org/10.1163/156856206776986288.
11. Chung T.-W., Yang M.-G., Liu D.-Z., Chen W.-P., Pan C.-I., Wang S.-S. Enhancing growth human endothelial cells on Arg-Gly-Asp (RGD) embedded poly(epsilon-caprolactone) (PCL) surface with nanometer scale of surface disturbance. J Biomed Mater Res A 2004; 72(2): 213–219, https://doi.org/10.1002/jbm.a.30225.
12. Zheng W., Guan D., Teng Y., Wang Z., Zhang S., Wang L., Kong D., Zhang J. Functionalization of PCL fibrous membrane with RGD peptide by a naturally occurring condensation reaction. Chinese Science Bulletin 2014; 59(22): 2776–2784, https://doi.org/10.1007/s11434-014-0336-0.
13. Gabriel M., Nazmi K., Dahm M., Zentner A., Vahl C.-F., Strand D. Covalent RGD modification of the inner pore surface of polycaprolactone scaffolds. J Biomater Sci Polym Ed 2012; 23(7): 941–953, https://doi.org/10.1163/092050611x566793.
14. Antonova L.V., Silnikov V.N., Khanova M.Yu., Koroleva L.S., Serpokrilova I.Yu., Velikanova E.A., Matveeva V.G., Senokosova E.A., Mironov A.V., Krivkina E.O., Kudryavtseva Yu.A., Barbarash L.S. Adhesion, proliferation and viability of human umbilical vein endothelial cells cultured on the surface of biodegradable non-woven matrices modified with RGD peptides. Vestnik transplantologii i iskusstvennyh organov 2019; 21(1): 142–152, https://doi.org/10.15825/1995-1191-2019-1-142-152.
15. Antonova L.V., Silnikov V.N., Sevostyanova V.V., Yuzhalin A.E., Koroleva L.S., Velikanova E.A., Mironov A.V., Godovikova T.S., Kutikhin A.G., Glushkova T.V., Serpokrylova I.Yu., Senokosova E.A., Matveeva V.G., Khanova M.Yu., Akentyeva T.N., Krivkina E.O., Kudryavtseva Yu.A., Barbarash L.S. Biocompatibility of small-diameter vascular grafts in different modes of RGD modification. Polymers 2019; 11(1): 174, https://doi.org/10.3390/polym11010174.
16. Lin H.B., Sun W., Mosher D.F., García-Echeverría C., Schaufelberger K., Lelkes P.I., Cooper S.L. Synthesis, surface, and cell-adhesion properties of polyurethanes containing covalently grafted RGD-peptides. J Biomed Mater Res 1994; 28(3): 329–342, https://doi.org/10.1002/jbm.820280307.
17. Parniak M.A., Lange G., Viswanatha T. Quantitative determination of monosubstituted guanidines: a comparative study of different procedures. J Biochem Biophys Methods 1983; 7(4): 267–276, https://doi.org/10.1016/0165-022x(83)90051-9.

Antonova L.V., Silnikov V.N., Glushkova T.V., Koroleva L.S., Serpokrilova I.Yu., Sevostyanova V.V., Krivkina E.O., Senokosova E.A., Mironov A.V., Kudryavtseva Yu.A., Barbarash L.S. Novel Technology of Modifying the Surface of Biodegradable Vascular Grafts with RGD Peptides: Effect on the Surface Structure and Physical and Mechanical Properties. Sovremennye tehnologii v medicine 2019; 11(3): 15, https://doi.org/10.17691/stm2019.11.3.02