To the content
3 . 2021

Effect of the polymer composition of tissue-engineered vascular patches loaded with vascular endothelial growth factor on their properties and remodeling in situ

Abstract

Background. Carotid endarterectomy with patch angioplasty is an effective treatment for carotid artery stenosis. However, available vascular patches have shortcomings such as thrombosis, restenosis, calcification, and other complications. Tissue-engineered scaffolds based on biodegradable polymers are promising alternative for angioplasty.

The aim of the study was to compare the patches made of poly(ε-caprolactone) (PCL) and a mixture of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) and PCL, and modified with vascular endothelial growth factor (VEGF).

Material and methods. The patches loaded with the growth factor were fabricated via emulsion electrospinning. The vascular patches were tested to assess their morphology, mechanical properties and platelet aggregation, as well as remodeling and calcification after implantation into the abdominal aorta of rats for up to 12 months by histological and immunofluorescence studies. 

Results. The incorporation of VEGF into polymer fibres reduced the rigidity of PCL and PHBV/PCL and degree of platelet aggregation upon contact with scaffolds. PHBV/PCL/VEGF patches were completely endothelialized after 3 months of implantation into the vascular wall, and PCL/VEGF samples had an endothelial monolayer on the inner surface only after 12 months of implantation. Chronic granulomatous inflammation and thickening of the implant were observed in 50% of PCL patches with VEGF after 12 months of implantation, and extensive calcium deposits were found in all PCL/VEGF samples. The cell colonization of PHBV/PCL/VEGF showed no signs of chronic inflammation, and small areas of calcification were presented in 66.7% of cases after 12 months of implantation.

Conclusion. PHBV/PCL/VEGF patches have better biocompatibility and are more suitable for vascular wall reconstruction as compared to PCL/VEGF.

Keywords:vascular patch, tissue engineering, poly (3-hydroxybutyrate-co-3-hydroxyvalerate, poly(e-caprolactone), vascular endothelial growth factor, biodegradable polymers, endothelialisation

Funding. This work was supported by a comprehensive program of fundamental scientific research of the Siberian Branch of the Russian Academy of Sciences within the framework of the fundamental theme of the Research Institute KPSSZ No. 0546-2019-0002 "Pathogenetic substantiation of the development of implants for cardiovascular surgery based on biocompatible materials, with the implementation of a patient-oriented approach using mathematical modeling, tissue engineering and genomic predictors".
Conflict of interest. The authors declare no conflict of interest.
For citation: Sevostianova V.V., Mironov A.V., Antonova L.V., Krivkina E.O., Matveeva V.G., Velikanova E.A., Glushkova T.V., Akentyeva T.N., Barbarash L.S. Effect of the polymer composition of tissue-engineered vascular patches loaded with vascular endothelial growth factor on their properties and remodeling in situ. Clinical and Experimental Surgery. Petrovsky Journal. 2021; 9 (3): 25-36. DOI: https://doi.org/10.33029/2308-1198-2021-9-3-25-36 (in Russian)

References

1.    Oldenburg W.A., Almerey T., Selim M., Farres H., Hakaim A.G. Durability of carotid endarterectomy with bovine pericardial patch. Ann Vasc Surg. 2018; 50: 218-24. DOI: https://doi.org/10.10167j.avsg.2017.11.062

2. Gavrilenko A.V., Kuklin A.V., Fomina V.V. Conventional and eversion carotid endarterectomy for internal carotid artery stenosis. Khirurgiya. Zhurnal imeni N.I. Pirogova [Surgery. The Journal Named after N.I. Pirogov]. 2018; (2): 87-92. DOI: https://doi.org/10.17116/hirurg-ia2018287-92 (in Russian)

3.    Huizing E., Vos C.G., Hulsebos R.G., van den Ak-ker P.J., Borst G.J., UnlU Q. Patch angioplasty or primary closure following carotid endarterectomy for symptomatic carotid artery stenosis. Surg J (NY). 2018; 4 (2): e96-101. DOI: https://doi.org/10.1055/s-0038-1655757

4.    Naylor A.R., Ricco J.B., de Borst G.J., Debus S., de Haro J., Halliday A., et al. Editor’s choice e management of atherosclerotic carotid and vertebral artery disease: 2017 clinical practice guidelines of the European Society for Vascular Surgery (ESVS). Eur J Vasc Endovasc Surg. 2018; 55: 3-81. DOI: https://doi.org/10.1016/j.ejvs.2017.06.021

5. Yarikov A.V., Balyabin A.V., Yashin K.S., Mukhin A.S. Surgical treatment modalities of carotid artery stenosis (review). Sovremennye tekhnologii v meditsine [Modern Technologies in Medicine]. 2015; 7 (4): 189200 DOI:    https://doi.org/10.17691/stm2015.7.4.25 (in Russian)

6.    Ren S., Li X., Wen J., Zhang W., Liu P Systematic review of randomized controlled trials of different types of patch materials during carotid endarterectomy. PLoS One. 2013; 8 (1): e55050. DOI: https://doi.org/10.1371/journal.pone.0055050

7.    Saporito W.F., Pires A.C., Cardoso S.H., Correa J.A., de Abreu L.C., Valenti V.E., et al. Bovine pericardium retail preserved in glutaraldehyde and used as a vascular patch. BMC Surg. 2011; 11: 37. DOI: https://doi.org/10.1186/1471-2482-11-37

8.    Kim C.-W., Kim M.-K., Kim S.-G., Park Y.-W., Park Y.-T., Kim D.-W., et al. Angioplasty using 4-hexylres-orcinol-incorporated silk vascular patch in rat carotid defect model. Appl Sci. 2018; 8: 2388. DOI: https://doi.org/10.3390/app8122388.8

9.    Smith R.J., Yi T., Nasiri B., Breuer C.K., Andrea-dis S.T. Implantation of VEGF-functionalized cell-free vascular grafts: regenerative and immunological response. FASEB J. 2019; 3 (4): 5089-100. DOI: https://doi.org/10.1096/fj.201801856R

10.    Shin Y.M., Lee Y.B., Kim S.J., Kang J.K., Park J.C., Jang W., et al. Mussel-inspired immobilization of vascular endothelial growth factor (VEGF) for enhanced en-dothelialization of vascular grafts. Biomacromolecules. 2012; 13 (7): 2020-8. DOI: https://doi.org/10.1021/bm300194b

11. Antonova L.V., Sevostyanova V.V., Mironov A.V., Krivkina E.O., Velikanova E.A., Matveeva V.G., et al. 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: https://doi.org/10.17802/2306-1278-2018-7-2-25-36

12.    Krilleke D., Ng Y.S.E., Shima D.T. The heparinbinding domain confers diverse functions of VEGF-A in development and disease: a structure-function study. Biochem Soc Trans. 2009; 37: 1201-6. DOI: https://doi.org/10.1042/BST0371201.13

13.    Miyazu K., Kawahara D., Ohtake H., Watanabe G., Matsuda T. Luminal surface design of electrospun small-diameter graft aiming at in situ capture of endothelial progenitor cell. J Biomed Mater Res B Appl Biomat. 2010; 94 (1): 53-63. DOI: https://doi.org/10.1002/jbm.b.31623

14. Sevostianova V.V., Mironov A.V., Krivkina E.O., Khanova M.V., Velikanova E.A., Matveeva V.G., et al. Biodegradable poly(s-caprolactone) VEGF-containing vascular patches for angioplasty. In: AIP Conference Proceedings. 2019; 2167: 020321. DOI: https://doi.org/10.1063/1.5132188

15.    Sevost’yanova V.V., Mironov A.V., Antonova L.V., Krivkina E.O., Matveeva V.G., Velikanova E.A., et al. Tissue-engineered patch modified by vascular endothelial growth factor for reconstruction of vascular wall. Patologiya krovoobrashcheniya i kardiokhirurgiya [Pathology of Blood Circulation and Cardiac Surgery]. 2020; 24 (4): 114-28. DOI: https://doi.org/10.21688/1681-3472-2020-4-114-128 (in Russian)

16.    Arimura S., Kawahara K., Biswas K.K.,Abeyama K., Tabata M., Shimoda T., et al. Hydroxyapatite formed on/in agarose gel induces activation of blood coagulation and platelets aggregation. J Biomed Mater Res B Appl Biomater. 2007; 81 (2): 456-61. DOI: https://doi.org/10.1002/jbm.b.30684

17.    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: https://doi.org/10.1080/09205063.2015.1030992

18.    Catto V., Fare S., Freddi G., Tanzi M.C. Vascular tissue engineering: recent advances in small diameter blood vessel regeneration. ISRN Vasc Med. 2014; 2014: 923030. DOI: https://doi.org/10.1155/2014/923030

19.    Singh C., Wong C.S., Wang X. Medical textiles as vascular implants and their success to mimic natural arteries. J Funct Biomater. 2015; 6 (3): 500-25. DOI: https://doi.org/10.3390/jfb6030500

20. Glushkova T.V., Sevost’yanova V.V., Antonova L.V., Klyshnikov K.Yu., Ovcharenko E.A., Sergeeva E.A., et al. Biomechanical remodeling of biodegradable small-diameter vascular grafts in situ. Vestnik transplantologii i iskusstvennykh organov [Bulletin of Transplantology and Artificial Organs]. 2016; 18 (2): 99-109. DOI: https://doi.org/10.15825/1995-1191-2016-2-99-109  (in Russian)

21.    Muto A., Nishibe T., Dardik H., Dardik A. Patches for carotid artery endarterectomy: Current materials and prospects. J Vasc Surg. 2009; 50: 206-13. DOI: https://doi.org/10.1016/jjvs.2009.01.062

22. Sevostianova V.V., Antonova L.V., Mironov A.V., Yuzhalin A.E., Silnikov V.N., Glushkova T.V., et al. Biodegradable patches for arterial reconstruction modified with RGD peptides: results of an experimental study. ACS Omega. 2020; 5 (34): 21 700-11. DOI: https://doi.org/10.1021/acsomega.0c02593

23.    Tebaldi M.L., Maia A.L.C., Poletto F., Andrade F., Soares D.C.F. Poly(-3-hydroxybutyrate-co-3-hydroxyvaler-ate) (PHBV): Current advances in synthesis methodologies, antitumor applications and biocompatibility. J Drug Deliv Sci Technol. 2019; 51: 115-26. DOI: https://doi.org/10.1016/j.jddst.2019.02.007

24.    Abedalwafa M., Wang F., Wang L., Li C. Biodegradable poly-epsilon-caprolactone (PCL) for tissue engineering applications: a review. Rev Adv Mater Sci. 2013; 34: 123-40.

25.    Dolzhikov A.A., Kolpakov A.Y., Yarosh A.L., Molchanova A.S., Dolzhikova I.N. Giant foreign body cells and tissue reactions on the surface of implants. Chelovek i ego zdorov’e [Humans and Their Health].2017; (3): 86-94. DOI: https://doi.org/10.21626/vestnik/2017-3/15 (in Russian)

26.    New S.E., Goettsch C., Aikawa M., Marchini J.F., Shibasaki M., Yabusaki K., et al. Macrophage-derived matrix vesicles: an alternative novel mechanism for microcalcification in atherosclerotic plaques. Circ Res. 2013; 113: 72-7. DOI: https://doi.org/10.1161/CIRCRESAHA.113.301036

All articles in our journal are distributed under the Creative Commons Attribution 4.0 International License (CC BY 4.0 license)

CHIEF EDITOR
CHIEF EDITOR
Sergey L. Dzemeshkevich
MD, Professor (Moscow, Russia)

Journals of «GEOTAR-Media»