Immobilized Bisphosphonates as Potential Inhibitors of Bioprosthetic Calcification: Effects on Various Xenogeneic Cardiovascular Tissues

Calcification is the major factor limiting the clinical use of bioprostheses. It may be prevented by the immobilization of bisphosphonic compounds (BPs) on the biomaterial. In this study, we assessed the accumulation and structure of calcium phosphate deposits in collagen-rich bovine pericardium (Pe...

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Main Authors: Irina Y. Zhuravleva, Anna A. Dokuchaeva, Elena V. Karpova, Tatyana P. Timchenko, Anatoly T. Titov, Svetlana S. Shatskaya, Yuliya F. Polienko
Format: Article
Language:English
Published: MDPI AG 2021-12-01
Series:Biomedicines
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Online Access:https://www.mdpi.com/2227-9059/10/1/65
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author Irina Y. Zhuravleva
Anna A. Dokuchaeva
Elena V. Karpova
Tatyana P. Timchenko
Anatoly T. Titov
Svetlana S. Shatskaya
Yuliya F. Polienko
author_facet Irina Y. Zhuravleva
Anna A. Dokuchaeva
Elena V. Karpova
Tatyana P. Timchenko
Anatoly T. Titov
Svetlana S. Shatskaya
Yuliya F. Polienko
author_sort Irina Y. Zhuravleva
collection DOAJ
description Calcification is the major factor limiting the clinical use of bioprostheses. It may be prevented by the immobilization of bisphosphonic compounds (BPs) on the biomaterial. In this study, we assessed the accumulation and structure of calcium phosphate deposits in collagen-rich bovine pericardium (Pe) and elastin-rich porcine aortic wall (Ao) and bovine jugular vein wall (Ve) cross-linked with glutaraldehyde (GA) or diepoxy compound (DE). These tissues were then modified with pamidronic (PAM) acid or 2-(2′-carboxyethylamino)ethylidene-1,1-bisphosphonic (CEABA) acid. Tissue transformations were studied using Fourier-transform infrared spectroscopy. After subcutaneous implantation of the biomaterials in 220 rats, calcification dynamics were examined using atomic absorption spectrophotometry, light microscopy after von Kossa staining, and scanning electron microscopy coupled with energy-dispersive X-ray spectroscopy The calcium content in all GA-cross-linked tissues and DE-cross-linked Ao increased to 100–160 mg/g on day 60 after implantation. BPs prevented the accumulation of phosphates on the surface of all materials and most effectively inhibited calcification in GA-cross-linked Ao and DE-cross-linked Pe. PAM containing -OH in the R1 group was more effective than CEABA containing -H in R1. The calcification-inhibitory effect of BPs may be realized through their ability to block nucleation and prevent the growth of hydroxyapatite crystals.
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spelling doaj.art-fc09cabaa17a47b3b1ddf292f764da002023-11-23T13:03:12ZengMDPI AGBiomedicines2227-90592021-12-011016510.3390/biomedicines10010065Immobilized Bisphosphonates as Potential Inhibitors of Bioprosthetic Calcification: Effects on Various Xenogeneic Cardiovascular TissuesIrina Y. Zhuravleva0Anna A. Dokuchaeva1Elena V. Karpova2Tatyana P. Timchenko3Anatoly T. Titov4Svetlana S. Shatskaya5Yuliya F. Polienko6E. Meshalkin National Medical Research Center of the RF Ministry of Health, 15 Rechkunovskaya Street, 630055 Novosibirsk, RussiaE. Meshalkin National Medical Research Center of the RF Ministry of Health, 15 Rechkunovskaya Street, 630055 Novosibirsk, RussiaN.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry SB RAS, 9 Lavrentiev Avenue, 630090 Novosibirsk, RussiaE. Meshalkin National Medical Research Center of the RF Ministry of Health, 15 Rechkunovskaya Street, 630055 Novosibirsk, RussiaV. Sobolev Institute of Geology and Mineralogy SB RAS, 3 Academician Koptyug Avenue, 630090 Novosibirsk, RussiaInstitute of Solid State Chemistry and Mechanochemistry SB RAS, 18 Kutateladze Street, 630128 Novosibirsk, RussiaN.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry SB RAS, 9 Lavrentiev Avenue, 630090 Novosibirsk, RussiaCalcification is the major factor limiting the clinical use of bioprostheses. It may be prevented by the immobilization of bisphosphonic compounds (BPs) on the biomaterial. In this study, we assessed the accumulation and structure of calcium phosphate deposits in collagen-rich bovine pericardium (Pe) and elastin-rich porcine aortic wall (Ao) and bovine jugular vein wall (Ve) cross-linked with glutaraldehyde (GA) or diepoxy compound (DE). These tissues were then modified with pamidronic (PAM) acid or 2-(2′-carboxyethylamino)ethylidene-1,1-bisphosphonic (CEABA) acid. Tissue transformations were studied using Fourier-transform infrared spectroscopy. After subcutaneous implantation of the biomaterials in 220 rats, calcification dynamics were examined using atomic absorption spectrophotometry, light microscopy after von Kossa staining, and scanning electron microscopy coupled with energy-dispersive X-ray spectroscopy The calcium content in all GA-cross-linked tissues and DE-cross-linked Ao increased to 100–160 mg/g on day 60 after implantation. BPs prevented the accumulation of phosphates on the surface of all materials and most effectively inhibited calcification in GA-cross-linked Ao and DE-cross-linked Pe. PAM containing -OH in the R1 group was more effective than CEABA containing -H in R1. The calcification-inhibitory effect of BPs may be realized through their ability to block nucleation and prevent the growth of hydroxyapatite crystals.https://www.mdpi.com/2227-9059/10/1/65bioprosthetic calcificationbisphosphonateporcine aortic wallbovine jugular veincross-linkingglutaraldehyde
spellingShingle Irina Y. Zhuravleva
Anna A. Dokuchaeva
Elena V. Karpova
Tatyana P. Timchenko
Anatoly T. Titov
Svetlana S. Shatskaya
Yuliya F. Polienko
Immobilized Bisphosphonates as Potential Inhibitors of Bioprosthetic Calcification: Effects on Various Xenogeneic Cardiovascular Tissues
Biomedicines
bioprosthetic calcification
bisphosphonate
porcine aortic wall
bovine jugular vein
cross-linking
glutaraldehyde
title Immobilized Bisphosphonates as Potential Inhibitors of Bioprosthetic Calcification: Effects on Various Xenogeneic Cardiovascular Tissues
title_full Immobilized Bisphosphonates as Potential Inhibitors of Bioprosthetic Calcification: Effects on Various Xenogeneic Cardiovascular Tissues
title_fullStr Immobilized Bisphosphonates as Potential Inhibitors of Bioprosthetic Calcification: Effects on Various Xenogeneic Cardiovascular Tissues
title_full_unstemmed Immobilized Bisphosphonates as Potential Inhibitors of Bioprosthetic Calcification: Effects on Various Xenogeneic Cardiovascular Tissues
title_short Immobilized Bisphosphonates as Potential Inhibitors of Bioprosthetic Calcification: Effects on Various Xenogeneic Cardiovascular Tissues
title_sort immobilized bisphosphonates as potential inhibitors of bioprosthetic calcification effects on various xenogeneic cardiovascular tissues
topic bioprosthetic calcification
bisphosphonate
porcine aortic wall
bovine jugular vein
cross-linking
glutaraldehyde
url https://www.mdpi.com/2227-9059/10/1/65
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AT elenavkarpova immobilizedbisphosphonatesaspotentialinhibitorsofbioprostheticcalcificationeffectsonvariousxenogeneiccardiovasculartissues
AT tatyanaptimchenko immobilizedbisphosphonatesaspotentialinhibitorsofbioprostheticcalcificationeffectsonvariousxenogeneiccardiovasculartissues
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