IMPACT OF CYCLIC LOADING ON THE RESISTANCE OF EPOXY-TREATED BOVINE PERICARDIUM MODIFIED WITH POLYVINYL ALCOHOL TO CALCIFICATION AND PROTEOLYTIC DEGRADATION

Highlights:

• Epoxy-treated xenopericardium modified with polyvinyl alcohol has increased resistance to calcification and proteolytic degradation in vitro.
• Cyclic loads negatively affect fatigue life of studied material, moreover, this process is accompanied by deterioration of its anti-calcium and anti-enzyme properties. Additional studies aimed at improving the wear resistance of the hydrogel in the biological material are required.

Aim. To study the resistance of epoxy-treated bovine pericardium modified with polyvinyl alcohol to calcification and proteolytic degradation in collagenase after exposure to cyclic loading.

Material and methods. The epoxy-treated patches made with xenopericardium were treated with polyvinyl alcohol according to the original method, after that they were subjected to cyclic loading (70 million cycles) using the HiCycle wear tester system. Visualization of the surface and internal structure of the biomaterial was performed by scanning electron microscopy. The resistance to calcification was assessed by incubating the samples in a solution saturated with calcium ions and phosphate ions for 3 and 6 weeks, followed by quantitative measurement of the calcium by spectrophotometry. The susceptibility of the samples to proteolytic degradation was determined by weight loss after incubation in a solution of clostridial collagenase for 24 hours. The control group consisted of patches of unmodified epoxy-treated bovine pericardium.

Results. After cyclic loading, patches of xenopericardium modified with polyvinyl alcohol showed signs of fatigue (cracks on the surface and large cavities in the internal structure). Although cyclic loading significantly worsened the resistance of the modified tissue to calcification and proteolytic degradation (by 3 and 5 times, respectively, relative to the values obtained for patches stored under static conditions), patches from this group showed better results compared to unmodified patches. Thus, they contained 1.5 to 2 times less calcium after 3 and 6 weeks of incubation in a calcium-saturated solution. Mass loss after incubation in collagenase was 1.5 times lower for patches of modified biomaterial undergoing cyclic loading compared to unmodified patches.

Conclusion. The proposed modification method of the epoxy-treated xenopericardium with polyvinyl alcohol increases the resistance of biological tissue to calcification and proteolytic degradation. Although cyclic loading negatively affects the protective properties of the polymer coating over time, this type of modification can potentially slow down the degeneration of biomaterial used in manufacturing of bioprosthetic heart valves.

1. Velho T.R., Pereira R.M., Fernandes F., Guerra N.C., Ferreira R., Nobre Â. Bioprosthetic aortic valve degeneration: a review from a basic science perspective. Brazilian Journal of Cardiovascular Surgery. 2022; 37(2):239-250. doi:10.21470/1678-9741-2020-0635

2. Bax J.J., Delgado V. Bioprosthetic heart valves, thrombosis, anticoagulation, and imaging surveillance. JACC: Cardiovascular Interventions. 2017; 10(4):388-390. doi:10.1016/j.jcin.2017.01.017

3. Otto C.M., Nishimura R.A., Bonow R.O., Carabello B.A., Erwin J.P., Gentile F., Jneid H., Krieger E.V. et al. 2020 ACC/AHA guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Joint Committee on clinical practice guidelines. Circulation. 2021; 143(5):e72-e227. doi:10.1161/CIR.0000000000000923

4. Pibarot P., Dumesnil J.G. Prosthetic heart valves: selection of the optimal prosthesis and long-term management. Circulation. 2009; 119(7):1034-1048. doi:10.1161/CIRCULATIONAHA.108.778886

5. Tillquist M.N., Maddox T.M. Cardiac crossroads: deciding between mechanical or bioprosthetic heart valve replacement. Patient Preference and Adherence. 2011; 17(5):91-99. doi:10.2147/PPA.S16420

6. Dvir D., Bourguignon T., Otto C.M., Hahn R.T., Rosenhek R., Webb J.G., Treede H., Sarano M.E. et al. Standardized definition of structural valve degeneration for surgical and transcatheter bioprosthetic aortic valves. Circulation. 2018; 137(4):388-399. doi:10.1161/CIRCULATIONAHA.117.030729

7. Kostyunin A.E., Yuzhalin A.E., Rezvova M.A., Ovcharenko E.A., Glushkova T.V., Kutikhin A.G. Degeneration of bioprosthetic heart valves: update 2020. Journal of the American Heart Association. 2020; 9(19):e018506. doi:10.1161/JAHA.120.018506

8. Shetty R., Pibarot P., Audet A., Janvier R., Dagenais F., Perron J., Couture C., Voisine P., Després J.P., Mathieu P. Lipid-mediated inflammation and degeneration of bioprosthetic heart valves. European Journal of Clinical Investigation. 2009; 39(6):471-480. doi:10.1111/j.1365-2362.2009.02132.x

9. Simionescu A., Simionescu D.T., Deac R.F. Matrix metalloproteinases in the pathology of natural and bioprosthetic cardiac valves. Cardiovascular Pathology. 1996; 5(6):323-332. doi:10.1016/s1054-8807(96)00043-9

10. Ding K., Zheng C., Huang X., Zhang S., Li M., Lei Y., Wang Y. A PEGylation method of fabricating bioprosthetic heart valves based on glutaraldehyde and 2-amino-4-pentenoic acid co-cross linking with improved antithrombogenicity and cytocompatibility. Acta Biomaterialia. 2022; 144:279-291. doi:10.1016/j.actbio.2022.03.026

11. Kostyunin A.E., Rezvova M.A., Glushkova T.V., Shishkova D.K., Kutikhin A.G., Akentieva T.N., Ovcharenko E.A. Polyvinyl alcohol improves resistance of epoxy-treated bovine pericardium to calcification in vitro. The Russian Journal of Transplantation. 2023; 15(1):34-45. doi:10.23873/2074-0506-2023-15-1-34-45. (In Russian)

12. Stieglmeier F., Grab M., König F., Büch J., Hagl C., Thierfelder N. Mapping of bovine pericardium to enable a standardized acquirement of material for medical implants. Journal of the Mechanical Behavior of Biomedical Materials. 2021; 118:104432. doi:10.1016/j.jmbbm.2021.104432

13. Dalgliesh A.J., Parvizi M., Noble C., Griffiths L.G. Effect of cyclic deformation on xenogeneic heart valve biomaterials. PLoS One. 2019; 14(6):e0214656. doi:10.1371/journal.pone.0214656

14. Soares J.S., Feaver K.R., Zhang W., Kamensky D., Aggarwal A., Sacks M.S. Biomechanical behavior of bioprosthetic heart valve heterograft tissues: characterization, simulation, and performance. Cardiovasc Eng Technol. 2016; 7(4):309-351. doi:10.1007/s13239-016-0276-8

15. Shen M., Marie P., Farge D., Carpentier S., De Pollak C., Hott M., Chen L., Martinet B., Carpentier A. Osteopontin is associated with bioprosthetic heart valve calcification in humans. Comptes Rendus de l'Académie des Sciences - Series III. 1997; 320(1):49-57. doi:10.1016/s0764-4469(99)80086-9

16. Nkhwa S., Kemal E., Gurav N., Deb S. Dual polymer networks: a new strategy in expanding the repertoire of hydrogels for biomedical applications. Journal of Materials Science: Materials in Medicine.2019; 30:114. doi:10.1007/s10856-019-6316-9

17. Pazos V., Mongrain R., Tardif J.C. Polyvinyl alcohol cryogel: optimizing the parameters of cryogenic treatment using hyperelastic models. Journal of the Mechanical Behavior of Biomedical Materials. 2009; 2(5):542-549. doi:10.1016/j.jmbbm.2009.01.003

18. Tong X., Zheng J., Lu Y., Zhang Z., Cheng H. Swelling and mechanical behaviors of carbon nanotube/poly(vinyl alcohol) hybrid hydrogels. Materials Letters. 2007; 61(8-9):1704-1706. doi:10.1016/j.matlet.2006.07.115

19. Zheng Q., Javadi A., Sabo R., Cai Z., Gong S. Polyvinyl alcohol (PVA)–cellulose nanofibril (CNF)–multiwalled carbon nanotube (MWCNT) hybrid organic aerogels with superior mechanical properties. RSC Advances. 2013; 3(43):20816 doi:10.1039/c3ra42321b