Evaluation of the biocompatibility and antimicrobial properties of biodegradable vascular grafts of various polymer composition with atrombogenic and antimicrobial drug coating

Creation of vascular grafts with atrombogenic and antimicrobial coating is a very important area.

Objective: to evaluate the biocompatibility and antimicrobial properties of biodegradable vascular grafts of various polymer compositions with atrombogenic and antimicrobial drug coating.

Materials and methods. Modification of the surface of the biodegradable vascular grafts was performed through complexation with polyvinylpyrrolidone, which was polymerized with polymer scaffold surface by means of ionizing radiation at 10 and 15 kGy. Physical and mechanical properties, as well as hemocompatibility were evaluated. Bacteriological studies were carried out using test strains of gram-negative and gram-positive microorganisms: Klebsiella pneumoniae spp. ozaena No. 5055, Escherichia coli ATCC 25922, Staphylococcus aureus ATCC 25923, Proteus mirabillis ATCC3177, Pseudomonas aeruginosa.

Results. There was no influence of modifying manipulations with ionizing radiation on the physical and mechanical characteristics of biodegradable prostheses. Vascular grafts with atrombogenic and antimicrobial coatings exhibited atrombogenic properties upon contact with blood, reducing platelet aggregation by 5–7 times (p < 0.05). Also decrease in adhesion and platelets deformation index was found on the surface of drug-eluting scaffolds (for PCL-based prostheses, the latter decreased by 1.9 times relative to unmodified counterparts (p < 0.05), for PHBV/PCL-based prostheses – by 1.3 times relative to unmodified counterparts and 1.5 times relative to scaffolds with polyvinylpyrrolidone (p < 0.05). Bacteriological studies revealed a local inhibitory effect in the place where scaffolds with cationic amphiphile were applied on agar. No growth retardation zones were identified. Polymeric composition of the scaffolds and the used dose of ionizing radiation did not lead to a difference in the bacteriostatic properties of the scaffolds with amphiphile.

Conclusion. A full cycle of surface modification of biodegradable polymer prostheses based on both PCL and РHBV/PCL composition resulted in significant increase in the atrombogenic and antimicrobial properties of prostheses and did not worsen the physical-mechanical and biocompatible properties of the structures being developed.

1. Taggart DP. Current status of arterial grafts for coronary artery bypass grafting. Ann. Cardiothorac Surg. 2013; 2 (4): 427–430. doi: 10.3978/j.issn.2225-319X.2013.07.21. PMID: 23977618.

2. Altun G, Pulathan Z, Hemsinli D. Obturator bypass in the treatment of prosthetic graft infection: Classic but still effective. Turk Gogus Kalp Damar Cerrahisi Derg. 2018; 26 (3): 480–483. doi: 1010.5606/tgkdc.dergisi.2018.15744. PMID: 32082784.

3. Gentili A, Di Pumpo M, La Milia DI, Vallone D, Vangi G, Corbo MI et al. A Six-Year Point Prevalence Survey of Healthcare-Associated Infections in an Italian Teaching Acute Care Hospital. Int J Environ Res Public Health. 2020; 17 (21): 7724. doi: 10.3390/ijerph17217724. PMID: 33105772.

4. Welborn MB, Valentine RJ. Vascular infection. In Vascular Medicine; 2006. p. 859–879. Elsevier Inc. doi: 10.1016/B978-0-7216-0284-4.50067-1.

5. Sousa JV, Antunes L, Mendes C, Marinho A, Gonçalves A, Gonçalves Ó et al. Prosthetic vascular graft infections: a center experience. Angiologia e Cirurgia Vascular. 2014; 10 (2): 52–57. doi.org/10.1016/S1646-706X(14)70050-3.

6. Aslam S, Darouiche RO. Role of antibiofilm-antimicrobial agents in controlling device-related infections. Int J Artif Organs. 2011; 34 (9): 752–758. doi: 10.5301/ijao.5000024. PMID: 22094553.

7. Geipel U. Pathogenic organisms in hip joint infections. Int J Med Sci. 2009; 6 (5): 234–240. doi: 10.7150/ijms.6.234. PMID: 19834588.

8. Staneviciute E, Na’amnih W, Kavaliauskas P, Prakapaite R, Ridziauskas M, Kevlicius L et al. New in vitro model evaluating antiseptics’ efficacy in biofilm-associated Staphylococcus aureus prosthetic vascular graft infection. J Med Microbiol. 2019; 68 (3): 432–439. doi: 10.1099/jmm.0.000939. PMID: 30735113.

9. Zhao G, Hochwalt PC, Usui ML, Underwood RA, Singh PK, James GA et al. Delayed wound healing in diabetic (db/db) mice with Pseudomonas aeruginosa biofilm challenge: a model for the study of chronic wounds. Wound Repair Regen. 2010; 18 (5): 467–477. doi: 10.1111/j.1524-475X.2010.00608.x. PMID: 20731798.

10. Ng VW, Chan JM, Sardon H, Ono RJ, García JM, Yang YY et al. Antimicrobial hydrogels: a new weapon in the arsenal against multidrug-resistant infections. Adv Drug Deliv Rev. 2014; 78: 46–62. doi: 10.1016/j.addr.2014.10.028. PMID: 25450263.

11. Ghosh C, Haldar J. Membrane-Active Small Molecules: Designs Inspired by Antimicrobial Peptides. Chem Med Chem. 2015; 10 (10): 1606–1624. doi: 10.1002/cmdc.201500299. PMID: 26386345.

12. Molchanova N, Hansen PR, Franzyk H. Advances in Development of Antimicrobial Peptidomimetics as Potential Drugs. Molecules. 2017; 22 (9): 1430. doi: 10.3390/molecules22091430. PMID: 28850098.

13. Ghosh C, Haldar J. Membrane-Active Small Molecules: Designs Inspired by Antimicrobial Peptides. ChemMedChem. 2015; 10 (10): 1606–1624. doi: 10.1002/cmdc.201500299. PMID: 26386345.

14. Antonova LV, Sevostyanova VV, Rezvova MA et al. Technology of producing functionally active biodegradable small-diameter vascular prostheses with drug coating: patent # 2702239. Proprietor: Federalnoe gosudarstvennoe byudzhetnoe nauchnoe uchrezhdenie «Nauchno-issledovatelskij institut kompleksnykh problem serdechno-sosudistykh zabolevanij» (NII KPSSZ) (RU); № 2019119912; effective date for property rights: 25.06.2019; registration date: 07.10.2019, Bull. № 28. [In Russ].

15. Fedorova AA, Azzami K, Ryabchikova EI, Spitsyna YE, Silnikov VN, Ritter W et al. Inactivation of a non-enveloped RNA virus by artificial ribonucleases: honey bees and acute bee paralysis virus as a new experimental model for in vivo antiviral activity assessment. Antiviral Res. 2011; 91 (3): 267–277. doi: 10.1016/j.antiviral.2011.06.011. PMID: 21722669.

16. Yarinich LA, Burakova EA, Zakharov BA, Boldyreva EV, Babkina IN, Tikunova NV et al. Synthesis and structureactivity relationship of novel 1,4-diazabicyclo[2.2.2] octane derivatives as potent antimicrobial agents. Eur J Med Chem. 2015; 95: 563–573. doi: 10.1016/j.ejmech.2015.03.033. PMID: 25867737.

17. Burakova EA, Saranina IV, Tikunova NV, Nazarkinaa ZK, Laktionova PP, Karpinskaya LA et al. Biological evaluation of tetracationic compounds based on two 1,4-diazabicyclo[2.2.2]octane moieties connected by different linkers. Bioorg Med Chem. 2016; 24 (22): 6012–6020. doi: 10.1016/j.bmc.2016.09.064. PMID: 27720324.

18. Ye X, Wang Z, Zhang X, Zhou M, Cai L. Hemocompatibility research on the micro-structure surface of a bionic heart valve. Biomed Mater Eng. 2014; 24 (6): 2361– 2369. doi: 10.3233/BME-141049. PMID: 25226936.

19. Shen X, Su F, Dong J, Fan Z, Duan Y, Li S. In vitro biocompatibility evaluation of bioresorbable copolymers prepared from L-lactide, 1, 3-trimethylene carbonate, and glycolide for cardiovascular applications. J Biomater Sci Polym Ed. 2015; 26 (8): 497–514. doi: 10.1080/09205063.2015.1030992. PMID: 25783945.

20. Jung F, Braune S, Lendlein A. Haemocompatibility testing of biomaterials using human platelets. Clin Hemorheol Microcirc. 2013; 53 (1–2): 97–115. doi: 10.3233/CH-2012-1579. PMID: 22954639.

21. Bai J, Dai J, Li G. Electrospun composites of PHBV/ pearl powder for bone repairing. Progress in Natural Science: Materials International. 2015; 25 (4): 327–333. doi: 10.1016/j.pnsc.2015.07.004.

22. Lyu JS, Lee JS, Han J. Development of a biodegradable polycaprolactone film incorporated with an antimicrobial agent via an extrusion process. Sci Rep. 2019; 9 (1): 20236. doi: 10.1038/s41598-019-56757-5. PMID: 31882928.

23. Mireles LK, Wu MR, Saadeh N, Yahia H, Sacher E. Physicochemical Characterization of Polyvinyl Pyrrolidone: A Tale of Two Polyvinyl Pyrrolidones. ACS Omega. 2020; 5 (47): 30461–30467. doi: 10.1021/acsomega.0c04010. PMID: 33283094.

24. Källrot M, Edlund U, Albertsson AC. Surface functionalization of degradable polymers by covalent grafting. Biomaterials. 2006; 27 (9): 1788–1796. doi: 10.1016/j.biomaterials.2005.10.010. PMID: 16257444.