FEATURES OF POLYURETHANE MATRIX REMODELING IN SHEEP MODEL EXPERIMENTS

Highlights

The article describes the features of remodeling of polyurethane matrices during long-term implantation into the vascular bed of sheep. The results indicate high biocompatibility of polyurethane and resistance to bioresorption. The obtained data are significant for the development of medical products for cardiovascular surgery, in particular, biodegradable vascular prostheses.

Abstract

Aim. To evaluate the features of polyurethane remodeling in a long-term experiment on a large animal model.

Methods. Matrices made of 12% polyurethane solution in chloroform were manufactured by electrospinning at the Nanon-01A nanofiber electrospinning system (MIC, Japan). Matrix samples in the form of patches were implanted into the carotid arteries of sheep (n = 3) for a period of 6 months. The patency of vessels with implanted matrices was assessed after 2, 4 and 6 months using a portable hand-carried color Doppler - M7 Premium Ultrasound Machine (Mindray, China). The structure of the matrix surface before and after implantation was studied using an S-3400N scanning electron microscope (Hitachi, Japan). Histological examination of the explanted samples was carried out using an AXIO Imager A1 microscope (Carl Zeiss, Oberkochen, Germany) with previous staining of matrix sections with hematoxylin-eosin, Van Gieson and alizarin red C. Data processing was performed using the Statistica 6.0 software.

Results. After 2, 4 and 6 months of implantation of polyurethane matrices into the carotid artery of sheep, complete patency of the carotid arteries was revealed. Macroscopically, after 6 months of implantation, the matrix completely resembled the carotid artery wall due to the full consolidation of the matrix with the artery wall and remodeling. Layers of newly formed vascular tissue – neointima and neoadventitia – were formed on the basis of the matrix. Histological examination revealed the structural integrity of the matrix without signs of inflammation and calcification both in the matrix structure and adjacent tissues.

Conclusion. The biological inertia of polyurethane matrices with signs of remodeling was noted, which indicates a high biocompatibility of the material. Resistance to bioresorption and the ability to keep the frame of the product for a long time allows us to consider polyurethane as a suitable material for the formation of anti-aneurysmal protection of biodegradable vascular prostheses.

1. Radke D, Jia W, Sharma D, Fena K, Wang G, Goldman J, Zhao F. Tissue Engineering at the Blood-Contacting Surface: A Review of Challenges and Strategies in Vascular Graft Development. Adv Healthc Mater. 2018; 7(15): e1701461. doi: 10.1002/adhm.201701461.

2. Bergmeister H, Strobl M, Grasl C, Liska R, Schima H. Tissue engineering of vascular grafts. Eur. Surg. 2013; 45: 187-193. doi: 10.1007/s10353-013-0224-x.

3. van der Slegt J, Steunenberg SL, Donker JMW, Veen EJ, Ho GH, de Groot HG, van der Laan L. The current position of precuffed expanded polytetrafluoroethylene bypass grafts in peripheral vascular surgery. J. Vasc. Surg. 2014; 60 (1): 120–128. doi:10.1016/j.jvs.2014.01.062.

4. Antonova LV, Sevostyanova VV, Mironov AV, Krivkina EO, Velikanova EA, Matveeva VG, Glushkova TV, Elgudin YaL, Barbarash LS. In situ vascular tissue remodeling using biodegradable tubular scaffolds with incorporated growth factors and chemoattractant molecules. Complex Issues of Cardiovascular Diseases. 2018; 7 (2): 25-36. doi:10.17802/2306-1278-2018-7-2-25-36.

5. Tan W, Boodagh P, Selvakumar PP, Keyser S. Strategies to counteract adverse remodeling of vascular graft: A 3D view of current graft innovations. Front. Bioeng. Biotechnol. 2023; 10: 1097334. doi: 10.3389/fbioe.2022.1097334.

6. Xie X, Wu Q, Liu Y, Chen C, Chen Z, Xie C, Song M, Jiang Z, Qi X, Liu S, Tang Z, Wu Z. Vascular endothelial growth factor attenuates neointimal hyperplasia of decellularized smalldiameter vascular grafts by modulating the local inflammatory response. Front. Bioeng. Biotechnol. 2022; 10: 1066266. doi: 10.3389/fbioe.2022.1066266.

7. Zhang Q, Bosch-Rué È, Pérez RA, Truskey GA. Biofabrication of tissue engineering vascular systems. Apl. Bioeng. 2021; 5 (2): 021507. doi:10.1063/5.0039628.

8. Stegmayr B, Willems C, Groth T, Martins A, Neves NM, Mottaghy K, Remuzzi A, Walpoth B. Arteriovenous access in hemodialysis: A multidisciplinary perspective for future solutions. Int. J. Artif. Organs/ 2021; 44 (1): 3–16. doi:10.1177/0391398820922231.

9. Sassi S, Watanabe T, Shinoka T. Scaffold and Cell-Based Tissue Engineering Approaches as Alternative Therapy for Blood Vessel Disease. Preprints.org 2023, 2023050712. doi.org/10.20944/preprints202305.0712.v1.

10. Tissue-engineered Vascular Grafts. Walpoth BH, Bergmeister H, Bowlin GL, Kong D, Rotmans JI, Zilla P, editors. Cham: Springer International Publishing, 2020. 588 p. doi:10.1007/978-3-030-05336-9.

11. Eilenberg M, Enayati M, Ehebruster D, Grasl C, Walter I, Messner B, Baudis S, Potzmann P, Kaun C, Podesser BK, Wojta J, Bergmeister H. Long Term Evaluation of Nanofibrous, Bioabsorbable Polycarbonate Urethane Grafts for Small Diameter Vessel Replacement in Rodents. Eur J Vasc Endovasc Surg. 2020; 59: 643-652.

12. Grasl C, Bergmeister H, Stoiber M, Schima H, Weigel G. Electrospun polyurethane vascular grafts: In vitro mechanical behavior and endothelial adhesion molecule expression. Journal of Biomedical Materials Research Part A. 2009; 93: 716-723. doi:10.1002/jbm.a.32584.

13. Kucinska-Lipka J, Gubanska I, Janik H, Sienkiewicz M. Fabrication of polyurethane and polyurethane based composite fibres by the electrospinning technique for soft tissue engineering of cardiovascular system. Materials Science and Engineering: C. 2015; 46:166-176. doi.org/10.1016/j.msec.2014.10.027.

14. Grasl C, Stoiber M, Rohrich M, Moscato F, Bergmeister H. Heinrich Schima. Electrospinning of small diameter vascular grafts with preferential fiber directions and comparison of their mechanical behavior with native rat aortas. Materials Science & Engineering C. 2021; 124: 112085. doi.org/10.1016/j.msec.2021.112085.

15. Ghanbari E, Solouk A, Mehdinavaz Aghdam R, Haghbin Nazarpak M, Ahmadi Tafti SH. A novel substrate based on electrospun polyurethane nanofibers and electrosprayed polyvinyl alcohol microparticles for recombinant human erythropoietin delivery. J Biomed Mater Res A. 2022; 110(1): 181-195. doi:10.1002/jbm.a.37275

16. Zhen L, Creason SA, Simonovsky FI., Snyder JM, Lindhartsen SL, Mecwan MM, Johnson BW, Himmelfarb J, Ratner BD. Precision-porous polyurethane elastomers engineered for application in prohealing vascular grafts: Synthesis, fabrication and detailed biocompatibility assessment. Biomaterials. 2021; 279: 121174. doi:10.1016/j.biomaterials.2021.121174.

17. Fathi-Karkan S, Banimohamad-Shotorbani B, Saghati S, Rahbarghazi R, Davaran S. A critical review of fibrous polyurethane-based vascular tissue engineering scaffolds. J. Biol. Eng. 2022; 16 (1): 6. doi:10.1186/s13036-022-00286-9.