Vol. 30 No. 2 (2026)
ANALYTICAL REVIEW

Structural degeneration of biological conduits: mechanisms of calcification: an analytical review of calcification mechanisms

PDF (Русский) PDF HTML (Русский) JATS XML (Русский)
  • Nataliya R. Nichay
Nataliya R. Nichay
Meshalkin National Medical Research Center, Novosibirsk, Russian Federation
DOI: https://doi.org/10.21688/1681-3472-2026-2-20-33

Published 2026-08-10

Keywords

  • biological heart valves; mineralization mechanisms; pathological calcification; pulmonary valve conduit; structural valve degeneration

How to Cite

Nichay, N. R. . (2026). Structural degeneration of biological conduits: mechanisms of calcification: an analytical review of calcification mechanisms. Patologiya Krovoobrashcheniya I Kardiokhirurgiya, 30(2), 20–33. https://doi.org/10.21688/1681-3472-2026-2-20-33

Copyright (c) 2026 Nichay

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Abstract

Introduction: In congenital heart surgery, pulmonary valve replacement remains the most common valve substitution procedure. Pulmonary valved conduit implantation is essential for correcting most complex congenital heart defects and is performed five times more frequently than other valve replacements in children. However, all pulmonary valved conduits lack growth potential and inevitably undergo structural valve degeneration (SVD), limiting their long-term durability. Calcification constitutes the principal manifestation and predominant pathophysiological process of SVD.

Objective: To provide a comprehensive overview of the factors contributing to pathological calcification and their role in the pathogenesis of mineralization in biological conduits.

Materials: Literature sources, including both clinical and experimental studies, were analyzed.

Results: This narrative review examines the key drivers of pathological calcification, including recipient metabolic and immune factors, biomaterial structure and composition, and mechanical stress on the implant.

Conclusions: Understanding the basic mechanisms of biomaterial mineralization is essential for addressing early prosthesis dysfunction. Strategies targeting these mechanisms could underpin the development of next-generation conduits with greater resistance to tissue mineralization and improved long-term durability.

Received 15 May 2026. Revised 10 June 2026. Accepted 11 June 2026.

Funding
Research was carried out within the state assignment of Ministry of Health of Russian Federation (theme No. 124022500251-0). The funding source had no involvement in the study design; collection, analysis of data; writing of the report; or decision to submit the article for publication.

PDF (Русский) PDF HTML (Русский) JATS XML (Русский)

References

  1. Huyan Y., Chang Y., Song J. Application of homograft valved conduit in cardiac surgery. Front Cardiovasc Med. 2021;8:740871. PMID: 34712711; PMCID: PMC8545902. рttps://doi.org/10.3389/fcvm.2021.740871
  2. Schoen F.J., Levy R.J. Calcification of tissue heart valve substitutes: progress toward understanding and prevention. Ann Thorac Surg. 2005;79(3):1072-80. PMID: 15734452. https://doi.org/10.1016/j.athoracsur.2004.06.033
  3. Сойнов И.А., Ким А.И., Мовсесян Р.Р., Теплов П.В., Миллер А.Ю., Кулябин Ю.Ю., Авраменко А.А., Горбатиков К.В., Горбатых А.В., Налимов К.А., Абрамян М.А., Борисков М.В., Ковалев С.А., Свободов А.А., Архипов А.Н., Кривощеков Е.В., Амансахатова Е.Н., Тарасюк Е.С. Хирургическое лечение врожденных пороков сердца в Российской Федерации: данные национального регистра за 2024 год. Патология кровообращения и кардиохирургия. 2026;30(1):5-25. https://doi.org/10.21688/1681-3472-2026-1-5-25 Soynov I.A., Kim A.I., Movsesyan R.R., Teplov P.V., Miller A.Yu., Kulyabin Yu.Yu., Avramenko A.A., Gorbatikov K.V., Gorbatykh A.V., Nalimov K.A., Abramyan M.A., Boriskov M.V., Kovalev S.A., Svobodov A.A., Arkhipov A.N., Krivoshchekov E.V., Amansakhatova E.N., Tarasyuk E.S. Surgical Management of Congenital Heart Diseases in the Russian Federation: National Registry Data for 2024. Patologiya krovoobrashcheniya i kardiokhirurgiya = Circulation Pathology and Cardiac Surgery. 2026;30(1):5-25. (In Russ.) https://doi.org/10.21688/1681-3472-2026-1-5-25
  4. Herrmann J.L., Larson E.E., Mastropietro C.W., Rodefeld M.D., Turrentine M.W., Nozaki R., Brown J.W. Right ventricular outflow tract reconstruction in infant truncus arteriosus: a 37-year experience. Ann Thorac Surg. 2020;110(2):630-637. PMID: 31904368. https://doi.org/10.1016/j.athoracsur.2019.11.023
  5. Harris A.G., Iacobazzi D., Caputo M., Bartoli-Leonard F. Graft rejection in paediatric congenital heart disease. Transl Pediatr. 2023;12(8):1572-1591. PMID: 37692547; PMCID: PMC10485650. https://doi.org/10.21037/tp-23-80
  6. Crago M., Winlaw D.S., Farajikhah S., Dehghani F., Naficy S. Pediatric pulmonary valve replacements: Clinical challenges and emerging technologies. Bioeng Transl Med. 2023;8(4):e10501. PMID: 37476058; PMCID: PMC10354783. https://doi.org/10.1002/btm2.10501
  7. Ong K., Boone R., Gao M., Carere R., Webb J., Kiess M., Grewal J. Right ventricle to pulmonary artery conduit reoperations in patients with tetralogy of Fallot or pulmonary atresia associated with ventricular septal defect. Am J Cardiol. 2013;111(11):1638-43. PMID: 23481618. https://doi.org/10.1016/j.amjcard.2013.01.337
  8. Dave H., Mueggler O., Comber M., Enodien B., Nikolaou G., Bauersfeld U., Jenni R., Bettex D., Prêtre R. Risk factor analysis of 170 single-institutional contegra implantations in pulmonary position. Ann Thorac Surg. 2011;91(1):195-302; discussion 202-3. PMID: 21172512. https://doi.org/10.1016/j.athoracsur.2010.07.058
  9. Romeo J.L.R., Mokhles M.M., van de Woestijne P., de Jong P., van den Bosch A., van Beynum I.M., Takkenberg J.J.M., Bogers A.J.J.C. Long-term clinical outcome and echocardiographic function of homografts in the right ventricular outflow tract. Eur J Cardiothorac Surg. 2019;55(3):518-526. PMID: 30084965. https://doi.org/10.1093/ejcts/ezy265
  10. Mery C.M., Guzmán-Pruneda F.A., De León L.E., Zhang W., Terwelp M.D., Bocchini C.E., Adachi I., Heinle J.S., McKenzie E.D., Fraser C.D. Jr. Risk factors for development of endocarditis and reintervention in patients undergoing right ventricle to pulmonary artery valved conduit placement. J Thorac Cardiovasc Surg. 2016;151(2):432-9, 441.e1-2. PMID: 26670191. https://doi.org/10.1016/j.jtcvs.2015.10.069
  11. Alfieris G.M., Swartz M.F., Lehoux J., Bove E.L. Long-term survival and freedom from reoperation after placement of a pulmonary xenograft valved conduit. Ann Thorac Surg. 2016;102(2):602-7. PMID: 27154149. https://doi.org/10.1016/j.athoracsur.2016.02.045
  12. Журавлева И.Ю., Ничай Н.Р., Докучаева А.А., Сойнов И.А., Иванцов С.М., Кейль И.М., Омельченко А.Ю., Горбатых Ю.Н., Горбатых А.В. Клинико-морфологический анализ дисфункции кондуита Contegra у пациентов первого года жизни. Патология кровообращения и кардиохирургия. 2016;20(1):56-61. Zhuravleva I.Yu., Nichai N.R., Dokuchaeva A.A., Soinov I.A., Ivantsov S.M., Keil I.M., Omelchenko A.Yu., Gorbatykh Yu.N., Gorbatykh A.V. Clinical morphological analysis of Contegra dysfunction in infants. Patologiya Krovoobrashcheniya I Kardiokhirurgiya = Circulation Pathology and Cardiac Surgery. 2016;20(1):56-61. (In Russ.)
  13. Nichay N.R., Zhuravleva I.Y., Kulyabin Y.Y., Timchenko T.P., Voitov A.V., Kuznetsova E.V., Soynov I.A., Zubritskiy A.V., Bogachev-Prokophiev A.V., Karaskov A.M. In search of the best xenogeneic material for a paediatric conduit: an analysis of clinical data. Interact Cardiovasc Thorac Surg. 2018;27(1):34-41. PMID: 29452369. https://doi.org/10.1093/icvts/ivy029
  14. Schoen F.J., Levy R.J., Tam H., Vyavahare N. Pathological calcification of biomaterials. Biomaterials science. Wagner W.R., Sakiyama-Elbert S.E., Zhang G., Yaszemski M.J. (editors). Cambridge, Massachusetts: Academic Press; 2020; p. 973-994. https://doi.org/10.1016/B978-0-12-816137-1.00065-9
  15. Vidavsky N., Kunitake J.A.M.R., Estroff L.A. Multiple pathways for pathological calcification in the human body. Adv Healthc Mater. 2021;10(4):e2001271. PMID: 33274854; PMCID: PMC8724004. https://doi.org/10.1002/adhm.202001271
  16. Snijders B.M.G., Peters M.J.L., Koek H.L. Ectopic calcification: what do we know and what is the way forward? J Clin Med. 2023;12(11):3687. PMID: 37297880; PMCID: PMC10253322. https://doi.org/10.3390/jcm12113687
  17. Manji R.A., Hara H., Cooper D.K. Characterization of the cellular infiltrate in bioprosthetic heart valves explanted from patients with structural valve deterioration. Xenotransplantation. 2015;22(5):406-7. PMID: 26315116. https://doi.org/10.1111/xen.12187
  18. Kostyunin A., Mukhamadiyarov R., Glushkova T., Bogdanov L., Shishkova D., Osyaev N., Ovcharenko E., Kutikhin A. Ultrastructural pathology of atherosclerosis, calcific aortic valve disease, and bioprosthetic heart valve degeneration: commonalities and differences. Int J Mol Sci. 2020;21(20):7434. PMID: 33050133; PMCID: PMC7587971. https://doi.org/10.3390/ijms21207434
  19. Bozso S.J., Kang J.J.H., Basu R., Adam B., Dyck J.R.B., Oudit G.Y., Moon M.C., Freed D.H., Nagendran J., Nagendran J. Structural valve deterioration is linked to increased immune infiltrate and chemokine expression. J Cardiovasc Transl Res. 2021;14(3):503-512. PMID: 33089488. https://doi.org/10.1007/s12265-020-10080-x
  20. Senage T., Paul A., Le Tourneau T., Fellah-Hebia I., Vadori M., Bashir S., Galiñanes M., Bottio T., Gerosa G., Evangelista A., Badano L.P., Nassi A., Costa C., Cesare G., Manji R.A., Cueff de Monchy C., Piriou N., Capoulade R., Serfaty J.M., Guimbretière G., Dantan E., Ruiz-Majoral A., Coste du Fou G., Leviatan Ben-Arye S., Govani L., Yehuda S., Bachar Abramovitch S., Amon R., Reuven E.M., Atiya-Nasagi Y., Yu H., Iop L., Casós K., Kuguel S.G., Blasco-Lucas A., Permanyer E., Sbraga F., Llatjós R., Moreno-Gonzalez G., Sánchez-Martínez M., Breimer M.E., Holgersson J., Teneberg S., Pascual-Gilabert M., Nonell-Canals A., Takeuchi Y., Chen X., Mañez R., Roussel J.C., Soulillou J.P., Cozzi E., Padler-Karavani V. The role of antibody responses against glycans in bioprosthetic heart valve calcification and deterioration. Nat Med. 2022;28(2):283-294. PMID: 35177855; PMCID: PMC8863575. https://doi.org/10.1038/s41591-022-01682-w
  21. Manji R.A., Zhu L.F., Nijjar N.K., Rayner D.C., Korbutt G.S., Churchill T.A., Rajotte R.V., Koshal A., Ross D.B. Glutaraldehyde-fixed bioprosthetic heart valve conduits calcify and fail from xenograft rejection. Circulation. 2006;114(4):318-27. PMID: 16831988. https://doi.org/10.1161/CIRCULATIONAHA.105.549311
  22. Chong D.S.T., Constantinou J., Davis M., Hamilton G. Calcification of a synthetic renovascular graft in a child. EJVES Short Rep. 2016;33:13-15. PMID: 28856317; PMCID: PMC5576012. https://doi.org/10.1016/j.ejvssr.2016.06.001
  23. Mehta R.I., Mukherjee A.K., Patterson T.D., Fishbein M.C. Pathology of explanted polytetrafluoroethylene vascular grafts. Cardiovasc Pathol. 2011;20(4):213-21. PMID: 20619685. https://doi.org/10.1016/j.carpath.2010.06.005
  24. Kenneth Ward W. A review of the foreign-body response to subcutaneously-implanted devices: the role of macrophages and cytokines in biofouling and fibrosis. J Diabetes Sci Technol. 2008;2(5):768-77. PMID: 19885259; PMCID: PMC2769792. https://doi.org/10.1177/193229680800200504
  25. Lejay A., Bratu B., Kuntz S., Neumann N., Heim F., Chakfé N. Calcification of synthetic vascular grafts: a systematic review. EJVES Vasc Forum. 2023;60:1-7. PMID: 37416860; PMCID: PMC10320244. https://doi.org/10.1016/j.ejvsvf.2023.05.013
  26. Matilla L., Roncal C., Ibarrola J., Arrieta V., García-Peña A., Fernández-Celis A., Navarro A., Álvarez V., Gainza A., Orbe J., Cachofeiro V., Zalba G., Sádaba R., Rodríguez J.A., López-Andrés N. A Role for MMP-10 (matrix metalloproteinase-10) in calcific aortic valve stenosis. Arterioscler Thromb Vasc Biol. 2020;40(5):1370-1382. PMID: 32188274. https://doi.org/10.1161/ATVBAHA.120.314143
  27. Simionescu D.T., Lovekamp J.J., Vyavahare N.R. Extracellular matrix degrading enzymes are active in porcine stentless aortic bioprosthetic heart valves. J Biomed Mater Res A. 2003;66(4):755-63. PMID: 12926026. https://doi.org/10.1002/jbm.a.10066
  28. Busch E., Hohenester E., Timpl R., Paulsson M., Maurer P. Calcium affinity, cooperativity, and domain interactions of extracellular EF-hands present in BM-40. J Biol Chem. 2000;275(33):25508-15. PMID: 10801822. https://doi.org/10.1074/jbc.M001770200
  29. Zhu Y.S., Gu Y., Jiang C., Chen L. Osteonectin regulates the extracellular matrix mineralization of osteoblasts through P38 signaling pathway. J Cell Physiol. 2020;235(3):2220-2231. PMID: 31489629. https://doi.org/10.1002/jcp.29131
  30. Hunter G.K. Role of osteopontin in modulation of hydroxyapatite formation. Calcif Tissue Int. 2013;93(4):348-54. PMID: 23334303. https://doi.org/10.1007/s00223-013-9698-6
  31. Christian A.J., Lin H., Alferiev I.S., Connolly J.M., Ferrari G., Hazen S.L., Ischiropoulos H., Levy R.J. The susceptibility of bioprosthetic heart valve leaflets to oxidation. Biomaterials. 2014;35(7):2097-102. PMID: 24360721; PMCID: PMC3937592. https://doi.org/10.1016/j.biomaterials.2013.11.045
  32. Lee S., Levy R.J., Christian A.J., Hazen S.L., Frick N.E., Lai E.K., Grau J.B., Bavaria J.E., Ferrari G. Calcification and oxidative modifications are associated with progressive bioprosthetic heart valve dysfunction. J Am Heart Assoc. 2017;6(5):e005648. PMID: 28483776; PMCID: PMC5524104. https://doi.org/10.1161/JAHA.117.005648
  33. Кудрявцева Ю.А., Насонова М.В., Акентьева Т.Н., Бураго А.Ю., Журавлева И.Ю. Роль шовного материала в кальцификации кардиоваскулярных биопротезов. Комплексные проблемы сердечно-сосудистых заболеваний. 2013;(4):22-27. https://doi.org/10.17802/2306-1278-2013-4-22-27 Kudryavtseva Yu.A., Nasonova M.V., Akentieva T.N., Burago A.Yu., Zhuravlyova I.Yu. The role of suture material in the calcification of cardiovascular bioprosthesis. Complex Issues of Cardiovascular Diseases. 2013;(4):22-27. https://doi.org/10.17802/2306-1278-2013-4-22-27
  34. Gersak B. Presence of calcium in the vessel walls after end-to-end arterial anastomoses with polydioxanone and polypropylene sutures in growing dogs. J Thorac Cardiovasc Surg. 1993;106(4):587-91. PMID: 8412250.
  35. Nichay N.R., Dokuchaeva A.A., Kulyabin Y.Y., Boyarkin E.V., Kuznetsova E.V., Rusakova Y.L., Murashov I.S., Vaver A.A., Bogachev-Prokophiev A.V., Zhuravleva I.Y. Epoxy-versus glutaraldehyde-treated bovine jugular vein conduit for pulmonary valve replacement: a comparison of morphological changes in a pig model. Biomedicines. 2023;11(11):3101. PMID: 38002101; PMCID: PMC10669752. https://doi.org/10.3390/biomedicines11113101
  36. Makkar R.R., Blanke P., Leipsic J., Thourani V., Chakravarty T., Brown D., Trento A., Guyton R., Babaliaros V., Williams M., Jilaihawi H., Kodali S., George I., Lu M., McCabe J.M., Friedman J., Smalling R., Wong S.C., Yazdani S., Bhatt D.L., Bax J., Kapadia S., Herrmann H.C., Mack M., Leon M.B. Subclinical leaflet thrombosis in transcatheter and surgical bioprosthetic valves: PARTNER 3 cardiac computed tomography substudy. J Am Coll Cardiol. 2020;75(24):3003-3015. PMID: 32553252. https://doi.org/10.1016/j.jacc.2020.04.043
  37. Casula M., Fortuni F., Ferlini M., Mauri S., Rebuffi C., Rossini R., Ferrario M., Oltrona Visconti L. Subclinical leaflet thrombosis after transcatheter aortic valve replacement: a meaningless finding? A systematic review and meta-analysis. Eur Heart J Qual Care Clin Outcomes. 2021;7(1):107-108. PMID: 32479593 https://doi.org/10.1093/ehjqcco/qcaa047
  38. Cartlidge T.R.G., Doris M.K., Sellers S.L., Pawade T.A., White A.C., Pessotto R., Kwiecinski J., Fletcher A., Alcaide C., Lucatelli C., Densem C., Rudd J.H.F., van Beek E.J.R., Tavares A., Virmani R., Berman D., Leipsic J.A., Newby D.E., Dweck M.R. Detection and prediction of bioprosthetic aortic valve degeneration. J Am Coll Cardiol. 2019;73(10):1107-1119. PMID: 30871693; PMCID: PMC6424589. https://doi.org/10.1016/j.jacc.2018.12.056
  39. Ghazy T., Dittfeld C., Jannasch A., Haase M., Galli R., Plötze K., Waldow T., Matschke K. Subclinical endocarditis might be a hidden trigger of early prosthetic valve calcification: a histological study. Heart Surg Forum. 2018;21(4):E300-E304. PMID: 30084783. https://doi.org/10.1532/hsf.1740
  40. Kostyunin A.E., Glushkova T.V., Lobov A.A., Ovcharenko E.A., Zainullina B.R., Bogdanov L.A., Shishkova D.K., Markova V.E., Asanov M.A., Mukhamadiyarov R.A., Velikanova E.A., Akentyeva T.N., Rezvova M.A., Stasev A.N., Evtushenko A.V., Barbarash L.S., Kutikhin A.G. Proteolytic degradation is a major contributor to bioprosthetic heart valve failure. J Am Heart Assoc. 2023;12(1):e028215. PMID: 36565196; PMCID: PMC9973599. https://doi.org/10.1161/JAHA.122.028215
  41. Saleeb S.F., Newburger J.W., Geva T., Baird C.W., Gauvreau K., Padera R.F., Del Nido P.J., Borisuk M.J., Sanders S.P., Mayer J.E. Accelerated degeneration of a bovine pericardial bioprosthetic aortic valve in children and young adults. Circulation. 2014;130(1):51-60. PMID: 24756063. https://doi.org/10.1161/CIRCULATIONAHA.114.009835
  42. Gellis L., Baird C.W., Emani S., Borisuk M., Gauvreau K., Padera R.F. Jr, Sanders S.P. Morphologic and histologic findings in bioprosthetic valves explanted from the mitral position in children younger than 5 years of age. J Thorac Cardiovasc Surg. PMID: 29102206. 2018;155(2):746-752. https://doi.org/10.1016/j.jtcvs.2017.09.091
  43. Ничай Н.Р., Кулябин Ю.Ю., Журавлева И.Ю., Горбатых Ю.Н., Зубрицкий А.В., Войтов А.В., Сойнов И.А., Горбатых А.В., Богачев-Прокофьев А.В., Караськов А.М. Правосторонние ксенокондуиты у детей: анализ причин дисфункции. Кардиология и сердечно-сосудистая хирургия. 2019;12(3):173-182. https://doi.org/10.17116/kardio201912031173 Nichay N.R., Kulyabin Yu.Yu., Zhuravleva I.Yu., Gorbatykh Yu.N., Zubritskiy A.V., Voitov A.V., Soynov I.A., Gorbatykh A.V., Bogachev-Prokof’ev A.V., Karas’kov A.M.. Right-sided xenografts in children: analysis of dysfunction. Russian Journal of Cardiology and Cardiovascular Surgery. 2019;12(3):173‑182. (In Russ.) https://doi.org/10.17116/kardio201912031173
  44. Simon A.K., Hollander G.A., McMichael A. Evolution of the immune system in humans from infancy to old age. Proc Biol Sci. 2015;282(1821):20143085. PMID: 26702035; PMCID: PMC4707740. https://doi.org/10.1098/rspb.2014.3085
  45. Vásquez-Alvarez S., Bustamante-Villagomez S.K., Vazquez-Marroquin G., Porchia L.M., Pérez-Fuentes R., Torres-Rasgado E., Herrera-Fomperosa O., Montes-Arana I., Gonzalez-Mejia M.E. Metabolic age, an index based on basal metabolic rate, can predict individuals that are high risk of developing metabolic syndrome. High Blood Press Cardiovasc Prev. 2021;28(3):263-270. PMID: 33666897. https://doi.org/10.1007/s40292-021-00441-1
  46. Homann M., Haehnel J.C., Mendler N., Paek S.U., Holper K., Meisner H., Lange R. Reconstruction of the RVOT with valved biological conduits: 25 years experience with allografts and xenografts. Eur J Cardiothorac Surg. 2000;17(6):624-30. PMID: 10856850. https://doi.org/10.1016/s1010-7940(00)00414-0
  47. Bass J.K., Chan G.M. Calcium nutrition and metabolism during infancy. Nutrition. 2006;22(10):1057-66. PMID: 16831534. https://doi.org/10.1016/j.nut.2006.05.014
  48. Peacock M. Calcium metabolism in health and disease. Clin J Am Soc Nephrol. 2010;5 Suppl 1:S23-30. PMID: 20089499. https://doi.org/10.2215/CJN.05910809
  49. Zhuravleva I.Y., Karpova E.V., Dokuchaeva A.A., Titov A.T., Timchenko T.P., Vasilieva M.B. Calcification of various bioprosthetic materials in rats: is it really different? Int J Mol Sci. 2023;24(8):7274. PMID: 37108443; PMCID: PMC10139218. https://doi.org/10.3390/ijms24087274
  50. Xue Y., Kossar A.P., Abramov A., Frasca A., Sun M., Zyablitskaya M., Paik D., Kalfa D., Della Barbera M., Thiene G., Kozaki S., Kawashima T., Gorman J.H., Gorman R.C., Gillespie M.J., Carreon C.K., Sanders S.P., Levy R.J., Ferrari G. Age-related enhanced degeneration of bioprosthetic valves due to leaflet calcification, tissue crosslinking, and structural changes. Cardiovasc Res. 2023;119(1):302-315. PMID: 35020813; PMCID: PMC10022861. https://doi.org/10.1093/cvr/cvac002
  51. D’Alessandro C.C., Komninou M.A., Badria A.F., Korossis S., Koutsoukos P., Mavrilas D. Calcification assessment of bioprosthetic heart valve tissues using an improved in vitro model. IEEE Trans Biomed Eng. 2020;67(9):2453-2461. PMID: 31902749. https://doi.org/10.1109/TBME.2019.2963043
  52. Lockitch G., Halstead A.C., Albersheim S., MacCallum C., Quigley G. Age- and sex-specific pediatric reference intervals for biochemistryanalytes as measured with the Ektachem-700 analyzer. Clin Chem. 1988;34(8):1622-1625. PMID: 3402068.
  53. Pagana K.D., Pagana T.J., Pagana T.N. Mosby’s diagnostic and laboratory test reference-E-book. Elsevier Health Sciences: New York, NY, USA; 2014; 1104 p.
  54. Bacchetta J., Bernardor J., Garnier C., Naud C., Ranchin B. Hyperphosphatemia and chronic kidney disease: a major daily concern both in adults and in children. Calcif Tissue Int. 2021;108(1):116-127. PMID: 31996964. https://doi.org/10.1007/s00223-020-00665-8
  55. van den Bos T., Oosting J., Everts V., Beertsen W. Mineralization of alkaline phosphatase-complexed collagen implants in the rat in relation to serum inorganic phosphate. J Bone Miner Res. 1995;10(4):616-24. PMID: 7610933. https://doi.org/10.1002/jbmr.5650100415
  56. Turan S., Topcu B., Gökçe İ., Güran T., Atay Z., Omar A., Akçay T., Bereket A. Serum alkaline phosphatase levels in healthy children and evaluation of alkaline phosphatase z-scores in different types of rickets. J Clin Res Pediatr Endocrinol. 2011;3(1):7-11. PMID: 21448327; PMCID: PMC3065317. https://doi.org/10.4274/jcrpe.v3i1.02
  57. Barbarash O., Rutkovskaya N., Hryachkova O., Gruzdeva O., Uchasova E., Ponasenko A., Kondyukova N., Odarenko Y., Barbarash L. Impact of recipient-related factors on structural dysfunction of xenoaortic bioprosthetic heart valves. Patient Prefer Adherence. 2015;9:389-99. PMID: 25834408; PMCID: PMC4358689. https://doi.org/10.2147/PPA.S76001
  58. van Geemen D., Soares A.L., Oomen P.J., Driessen-Mol A., Janssen-van den Broek M.W., van den Bogaerdt A.J., Bogers A.J., Goumans M.J., Baaijens F.P., Bouten C.V. Age-dependent changes in geometry, tissue composition and mechanical properties of fetal to adult cryopreserved human heart valves. PLoS One. 2016;11(2):e0149020. PMID: 26867221; PMCID: PMC4750936. https://doi.org/10.1371/journal.pone.0149020
  59. Badria A.F., Koutsoukos P.G., Mavrilas D. Decellularized tissue-engineered heart valves calcification: what do animal and clinical studies tell us? J Mater Sci Mater Med. PMID: 33278023; PMCID: PMC7719105. 2020;31(12):132. https://doi.org/10.1007/s10856-020-06462-x
  60. Herrmann J.L., Brown J.W. Seven decades of valved right ventricular outflow tract reconstruction: the most common heart procedure in children. J Thorac Cardiovasc Surg. 2020;160(5):1284-1288. PMID: 32690409. https://doi.org/10.1016/j.jtcvs.2020.04.137
  61. Ничай Н.Р., Журавлева И.Ю., Кулябин Ю.Ю., Зыков И.С., Бояркин Е.В., Малахова О.Ю., Кузнецова Е.В., Тимченко Т.П., Русакова Я.Л., Мурашов И.С., Докучаева А.А., Богачев- Прокофьев А.В. Диэпокси-обработанный кондуит из яремной вены быка для протезирования легочной артерии. Патология кровообращения и кардиохирургия. 2022;26(4):19-32. https://dx.doi.org/10.21688/1681-3472-2022-4-19-32 Nichay N.R., Zhuravleva I.Yu., Kulyabin Yu.Yu., Zykov I.S., Boyarkin E.V., Malakhova O.Yu., Kuznetsova E.V., Timchenko T.P., Rusakova Yu.L., Murashov I.S., Dokuchaeva A.A., Bogachev-Prokophiev A.V. Diepoxy-treated bovine jugular vein conduit for pulmonary artery replacement. Patologiya Krovoobrashcheniya I Kardiokhirurgiya = Circulation Pathology and Cardiac Surgery, 2022;26(4):19-32. (In Russ.) https://dx.doi.org/10.21688/1681-3472-2022-4-19-32
  62. Zhuravleva I.Y., Nichay N.R., Kulyabin Y.Y., Timchenko T.P., Korobeinikov A.A., Polienko Y.F., Shatskaya S.S., Kuznetsova E.V., Voitov A.V., Bogachev-Prokophiev A.V., Karaskov A.M. In search of the best xenogeneic material for a paediatric conduit: an experimental study. Interact Cardiovasc Thorac Surg. 2018;26(5):738-744. PMID: 29346675. https://doi.org/10.1093/icvts/ivx445
  63. Mattson J.M., Zhang Y. Structural and functional differences between porcine aorta and vena cava. J Biomech Eng. 2017;139(7):0710071-8. PMID: 28303272; PMCID: PMC5467030. https://doi.org/10.1115/1.4036261
  64. Caballero A., Sulejmani F., Martin C., Pham T., Sun W. Evaluation of transcatheter heart valve biomaterials: biomechanical characterization of bovine and porcine pericardium. J Mech Behav Biomed Mater. 2017;75:486-494. PMID: 28826102; PMCID: PMC5614867. https://doi.org/10.1016/j.jmbbm.2017.08.013
  65. Landis W.J., Silver F.H., Freeman J.W. Collagen as a scaffold for biomimetic mineralization of vertebrate tissues. J Mater Chem. 2006;16:1495-1503. https://doi.org/10.1039/b505706j
  66. Журавлева И.Ю., Васильева М.Б., Тимченко Т.П., Кузнецова Е.В., Полиенко Ю.Ф., Ничай Н.Р., Григорьев И.А., Богачев-Прокофьев А.В. Кальцификация эластин-содержащих ксеногенных биоматериалов: влияние консервантов и бисфосфонатов. Сибирский научный медицинский журнал. 2017;37(6):28-37. Zhuravleva I.Y., Vasilyeva M.B., Timchenko T.P., Kuznetsova E.V., Polienko Y.F., Nichay N.R., Grigoryev I.A., Bogachev-Prokofiev A.V. Calcification of elastin-containing xenogenic biomaterials: influence of conservants and bisphosphonates. Siberian Scientific Medical Journal. 2017;37(6):28-37. (In Russ.)
  67. Attia R.Q., Raja S.G. Surgical pericardial heart valves: 50 years of evolution. Int J Surg. 2021;94:106121. PMID: 34543742. https://doi.org/10.1016/j.ijsu.2021.106121
  68. Zhuravleva I.Y., Karpova E.V., Dokuchaeva A.A., Kuznetsova E.V., Vladimirov S.V., Ksenofontov A.L., Nichay N.R. Bovine jugular vein conduit: what affects its elastomechanical properties and thermostability? J Biomed Mater Res A. 2022;110(2):394-408. PMID: 34390309. https://doi.org/10.1002/jbm.a.37296
  69. Kim K.M., Herrera G.A., Battarbee H.D. Role of glutaraldehyde in calcification of porcine aortic valve fibroblasts. Am J Pathol. 1999;154(3):843-52. PMID: 10079262; PMCID: PMC1866403. https://doi.org/10.1016/S0002-9440(10)65331-X
  70. Migneault I., Dartiguenave C., Bertrand M.J., Waldron K.C. Glutaraldehyde: behavior in aqueous solution, reaction with proteins, and application to enzyme crosslinking. Biotechniques. 2004;37(5):790-6, 798-802. PMID: 15560135. https://doi.org/10.2144/04375RV01
  71. Ferrans V.J., Boyce S.W., Billingham M.E., Jones M., Ishihara T., Roberts W.C. Calcific deposits in porcine bioprostheses: structure and pathogenesis. Am J Cardiol. 1980;46(5):721-34. PMID: 7192049. https://doi.org/10.1016/0002-9149(80)90421-x
  72. Барбараш Л.С., Барбараш Н.А., Журавлева И.Ю. Биопротезы клапанов сердца. Проблемы и перспективы. Кемерово; 1995. 399 с. Barbarash L.S., Barbarash N.A., Zhuravleva I.Yu. Bioprostheses of heart valves: problems and prospects. Kemerovo; 1995. 399 p. (In Russ.)
  73. Tsolaki E., Corso P., Zboray R., Avaro J., Appel C., Liebi M., Bertazzo S., Heinisch P.P., Carrel T., Obrist D., Herrmann I.K. Multiscale multimodal characterization and simulation of structural alterations in failed bioprosthetic heart valves. Acta Biomater. 2023;169:138-154. PMID: 37517619. https://doi.org/10.1016/j.actbio.2023.07.044
  74. Levy R.J., Schoen F.J., Sherman F.S., Nichols J., Hawley M.A., Lund S.A. Calcification of subcutaneously implanted type I collagen sponges. Effects of formaldehyde and glutaraldehyde pretreatments. Am J Pathol. 1986;122(1):71-82. PMID: 3079959; PMCID: PMC1888125.
  75. Guo G., Jin L., Jin W., Chen L., Lei Y., Wang Y. Radical polymerizationcrosslinking method for improving extracellular matrix stability in bioprosthetic heart valves with reduced potential for calcification and inflammatory response. Acta Biomater. 2018;82:44-55. PMID: 30326277. https://doi.org/10.1016/j.actbio.2018.10.017
  76. Guo G., Jin L., Wu B., He H., Yang F., Xu L., Lei Y., Wang Y. A method for simultaneously crosslinking and functionalizing extracellular matrix-based biomaterials as bioprosthetic heart valves with enhanced endothelialization and reduced inflammation. Acta Biomater. 2021;119:89-100. PMID: 33099025. https://doi.org/10.1016/j.actbio.2020.10.029
  77. Parashar A., Gourgas O., Lau K., Li J., Muiznieks L., Sharpe S., Davis E., Cerruti M., Murshed M. Elastin calcification in in vitro models and its prevention by MGP’s N-terminal peptide. J Struct Biol. 2021;213(1):107637. PMID: 33059036. https://doi.org/10.1016/j.jsb.2020.107637
  78. Rapoport H.S., Connolly J.M., Fulmer J., Dai N., Murti B.H., Gorman R.C., Gorman J.H., Alferiev I., Levy R.J. Mechanisms of the in vivo inhibition of calcification of bioprosthetic porcine aortic valve cusps and aortic wall with triglycidylamine/mercapto bisphosphonate. Biomaterials. 2007;28(4):690-9. PMID: 17027944; PMCID: PMC1829417. https://doi.org/10.1016/j.biomaterials.2006.09.029
  79. Vyavahare N., Ogle M., Schoen F.J., Levy R.J. Elastin calcification and its prevention with aluminum chloride pretreatment. Am J Pathol. 1999;155(3):973-82. PMID: 10487855; PMCID: PMC1866878. https://doi.org/10.1016/S0002-9440(10)65197-8
  80. Schräder C.U., Heinz A., Majovsky P., Karaman Mayack B., Brinckmann J., Sippl W., Schmelzer C.E.H. Elastin is heterogeneously cross-linked. J Biol Chem. 2018;293(39):15107- 15119. PMID: 30108173; PMCID: PMC6166741. https://doi.org/10.1074/jbc.RA118.004322
  81. Shin K., Kent J.E., Singh C., Fujimoto L.M., Yu J., Tian Y., Im W., Marassi F.M. Calcium and hydroxyapatite binding site of human vitronectin provides insights to abnormal deposit formation. Proc Natl Acad Sci U S A. 2020;117(31):18504-18510. PMID: 32699145; PMCID: PMC7414086. https://doi.org/10.1073/pnas.2007699117
  82. Roumeliotis S., Roumeliotis A., Dounousi E., Eleftheriadis T., Liakopoulos V. Biomarkers of vascular calcification in serum. Adv Clin Chem. 2020;98:91-147. PMID: 32564789. https://doi.org/10.1016/bs.acc.2020.02.004
  83. Leong J., Munnelly A., Liberio B., Cochrane L., Vyavahare N. Neomycin and carbodiimide crosslinking as an alternative to glutaraldehyde for enhanced durability of bioprosthetic heart valves. J Biomater Appl. 2013;27(8):948-60. PMID: 22207605. https://doi.org/10.1177/0885328211430542
  84. Kiełbik A., Szlasa W., Michel O., Szewczyk A., Tarek M., Saczko J., Kulbacka J. In vitro study of calcium microsecond electroporation of prostate adenocarcinoma cells. Molecules. 2020;25(22):5406. PMID: 33227916; PMCID: PMC7699241. https://doi.org/10.3390/molecules25225406
  85. Meuris B., De Praetere H., Strasly M., Trabucco P., Lai J.C., Verbrugghe P., Herijgers P. A novel tissue treatment to reduce mineralization of bovine pericardial heart valves. J Thorac Cardiovasc Surg. 2018;156(1):197-206. PMID: 29572021. https://doi.org/10.1016/j.jtcvs.2018.01.099
  86. Schoen F.J., Levy R.J. Bioprosthetic heart valve calcification: membrane- mediated events and alkaline phosphatase. Bone Miner. 1992;17(2):129-33. PMID: 1611297. https://doi.org/10.1016/0169-6009(92)90723-q
  87. Kim K.M. Cells, rather than extracellular matrix, nucleate apatite in glutaraldehyde-treated vascular tissue. J Biomed Mater Res. 2002;59(4):639-45. PMID: 11774325. https://doi.org/10.1002/jbm.10038
  88. Maizato M.J., Higa O.Z., Mathor M.B., Camillo M.A., Spencer P.J., Pitombo R.N., Zavaglia C.A., Leirner A.A. Glutaraldehyde-treated bovine pericardium: effects of lyophilization on cytotoxicity and residual aldehydes. Artif Organs. 2003;27(8):692-4. PMID: 12911342. https://doi.org/10.1046/j.1525-1594.2003.07275.x
  89. Lopez-Moya M., Melgar-Lesmes P., Kolandaivelu K., de la Torre Hernández J.M., Edelman E.R., Balcells M. Optimizing glutaraldehyde- fixed tissue heart valves with chondroitin sulfate hydrogel for endothelialization and shielding against deterioration. Biomacromolecules. 2018;19(4):1234- 1244. PMID: 29539266; PMCID: PMC6198652. https://doi.org/10.1021/acs.biomac.8b00077
  90. Umashankar P.R., Mohanan P.V., Kumari T.V. Glutaraldehyde treatment elicits toxic response compared to decellularization in bovine pericardium. Toxicol Int. PMID: 22736904; PMCID: PMC3339246. 2012;19(1):51-58. https://doi.org/10.4103/0971-6580.94513
  91. Nichay N.R., Dokuchaeva A.A., Kuznetsova E.V., Zhuravleva I.Y., Kulyabin Y.Y., Boyarkin E.V., Malakhova O.Y., Timchenko T.P., Rusakova Y.L., Bogachev-Prokophiev A.V. In vivo comparative study of calcification in diepoxy- and glutaraldehyde-treated bovine pericardial conduits for RVOT reconstruction. Prosthesis. 2025;7(3):67. https://doi.org/10.3390/prosthesis7030067
  92. Bell D., Prabhu S., Betts K., Justo R., Venugopal P., Karl T.R., Alphonso N. Durability of tissue-engineered bovine pericardium (CardioCel®) for a minimum of 24 months when used for the repair of congenital heart defects. Interact Cardiovasc Thorac Surg. 2019;28(2):284-290. PMID: 30101317. https://doi.org/10.1093/icvts/ivy246
  93. Larsen S.H., Dimopoulos K., Gatzoulis M.A., Uebing A., Shore D.F., Alonso-Gonzalez R., Kempny A. Surgical and percutaneous pulmonary valve replacement in England over the past two decades. Heart. 2019;105(12):932-937. PMID: 30700516. https://doi.org/10.1136/heartjnl-2018-314102
  94. Penteris M., Lampropoulos K. Surgical pulmonary valve redo versus transcatheter pulmonary valve replacement for tetralogy of Fallot patients. Expert Rev Cardiovasc Ther. 2025;23(3):87-95. PMID: 40122137. https://doi.org/10.1080/14779072.2025.2482926
  95. Caughron H., Kim D., Kamioka N., Lerakis S., Yousef A., Maini A., Reginauld S., Sahu A., Shashidharan S., Jokhadar M., Rodriguez F.H. 3rd., Book W.M., McConnell M., Block P.C., Babaliaros V. Repeat pulmonary valve replacement: similar intermediate-term outcomes with surgical and transcatheter procedures. JACC Cardiovasc Interv. 2018;11(24):2495-2503. PMID: 30503596. https://doi.org/10.1016/j.jcin.2018.07.042
  96. Vaesken A., Pelle A., Pavon-Djavid G., Rancic J., Chakfe N., Heim F. Heart valves from polyester fibers: a preliminary 6-month in vivo study. Biomed Tech (Berl). 2018;63(3):271-278. PMID: 28467307. https://doi.org/10.1515/bmt-2016-0242
  97. Taylor M.S., Shalaby S.W. Sutures. In: Biomaterials Science; Elsevier: Amsterdam, The Netherlands; 2013. pp. 1010–1024.
  98. Zhu F.J., Tong Y.L., Sheng Z.Y., Yao Y.M. Role of dendritic cells in the host response to biomaterials and their signaling pathways. Acta Biomater. 2019;94:132-144. PMID: 31108257. https://doi.org/10.1016/j.actbio.2019.05.038
  99. Liu J., Zhong S., Lan H., Meng X., Zhang H., Fan Y., Wang Y., Wang C., Wang Z. Mapping the calcification of bovine pericardium in rat model by enhanced micro-computed tomography. Biomaterials. 2014;35(29):8305-11. PMID: 24973299. https://doi.org/10.1016/j.biomaterials.2014.06.026
  100. Smith D.B., Sacks M.S., Pattany P.M., Schroeder R. Fatigue-induced changes in bioprosthetic heart valve three-dimensional geometry and the relation to tissue damage. J Heart Valve Dis. 1999;8(1):25-33. PMID: 10096478.
  101. Wells S.M., Sellaro T., Sacks M.S. Cyclic loading response of bioprosthetic heart valves: effects of fixation stress state on the collagen fiber architecture. Biomaterials. 2005;26(15):2611-9. PMID: 15585264. https://doi.org/10.1016/j.biomaterials.2004.06.046
  102. Liao K.K., Li X., John R., Amatya D.M., Joyce L.D., Park S.J., Bianco R., Bolman R.M. 3rd. Mechanical stress: an independent determinant of early bioprosthetic calcification in humans. Ann Thorac Surg. 2008;86(2):491-5. PMID: 18640322. https://doi.org/10.1016/j.athoracsur.2008.03.061
  103. Zareian R., Tseng J.C., Fraser R., Meganck J., Kilduff M., Sarraf M., Dvir D., Kheradvar A. Effect of stent crimping on calcification of transcatheter aortic valves. Interact Cardiovasc Thorac Surg. 2019;29(1):64-73. PMID: 30793744; PMCID: PMC6591709. https://doi.org/10.1093/icvts/ivz024
  104. Zhang W., Motiwale S., Hsu M.C., Sacks M.S. Simulating the time evolving geometry, mechanical properties, and fibrous structure of bioprosthetic heart valve leaflets under cyclic loading. J Mech Behav Biomed Mater. 2021;123:104745. PMID: 34482092; PMCID: PMC8482999. https://doi.org/10.1016/j.jmbbm.2021.104745
  105. Whelan A., Williams E., Fitzpatrick E., Murphy B.P., Gunning P.S., O’Reilly D., Lally C. Collagen fibre-mediated mechanical damage increases calcification of bovine pericardium for use in bioprosthetic heart valves. Acta Biomater. 2021;128:384-392. PMID: 33945880. https://doi.org/10.1016/j.actbio.2021.04.046
  106. Levy R.J., Schoen F.J., Levy J.T., Nelson A.C., Howard S.L., Oshry L.J. Biologic determinants of dystrophic calcification and osteocalcin deposition in glutaraldehyde-preserved porcine aortic valve leaflets implanted subcutaneously in rats. Am J Pathol. 1983;113(2):143-55. PMID: 6605687; PMCID: PMC1916380.
  107. Marathe S.P., Bell D., Betts K., Sayed S., Dunne B., Ward C., Whight C., Jalali H., Venugopal P., Andrews D., Alphonso N. Homografts versus stentless bioprosthetic valves in the pulmonary position: a multicentre propensity-matched comparison in patients younger than 20 years. Eur J Cardiothorac Surg. 2019;56(2):377- 384. PMID: 30753373. https://doi.org/10.1093/ejcts/ezz021
  108. Ничай Н.Р., Горбатых Ю.Н., Войтов А.В., Сойнов И.А., Кулябин Ю.Ю., Хапаев Т.С., Архипов А.Н., Аникина Н.В., Докучаева А.А., Богачев-Прокофьев А.В. Инфекционный эндокардит легочных кондуитов в педиатрической группе пациентов. Кардиология и сердечно-сосудистая хирургия. 2024;17(2):139‑151. https://doi.org/10.17116/kardio202417021139 Nichay N.R., Gorbatykh Y.N., Voitov A.V., Soynov I.A., Kulyabin Y.Y., Khapaev T.S., Arkhipov A.N., Anikina N.V., Dokuchaeva A.A., Bogachev- Prokofiev A.V. Infective endocarditis in pediatric patients with pulmonary graft. Russian Journal of Cardiology and Cardiovascular Surgery. 2024;17(2):139‑151. (In Russ.) https://doi.org/10.17116/kardio202417021139
  109. Kadeetham K., Samankatiwat P. Heterotopically-placed right ventricle-to-pulmonary artery conduit does not negatively affect outcomes. J Cardiothorac Surg. 2023;18(1):259. PMID: 37715260; PMCID: PMC10503057. https://doi.org/10.1186/s13019-023-02362-7
  110. Hazekamp M.G., Barron D.J., Dangel J., Homfray T., Jongbloed M.R.M., Voges I.; ESC Scientific Document Group. Consensus document on optimal management of patients with common arterial trunk. Eur J Cardiothorac Surg. 2021;60(1):7-33. PMID: 34017991. https://doi.org/10.1093/ejcts/ezaa423
  111. Jang W., Kim Y.J., Choi K., Lim H.G., Kim W.H., Lee J.R. Mid-term results of bioprosthetic pulmonary valve replacement in pulmonary regurgitation after tetralogy of Fallot repair. Eur J Cardiothorac Surg. 2012;42(1):e1-8. PMID: 22561653. https://doi.org/10.1093/ejcts/ezs219
  112. Naeem F., White T.J., Gaynor J.W., Zhang X., Ampah S., Glatz A.C., Mercer-Rosa L., Cohen M.S. Risk factors for early right ventricular- to-pulmonary artery conduit failure in congenital heart disease. JTCVS Open. 2025;28:450-458. PMID: 41473056; PMCID: PMC12745115. https://doi.org/10.1016/j.xjon.2025.09.051
  113. Bonilla-Ramirez C., Ibarra C., Binsalamah Z.M., Adachi I., Heinle J.S., McKenzie E.D., Caldarone C.A., Imamura M. Right ventricle to pulmonary artery conduit size is associated with conduit and pulmonary artery reinterventions after truncus arteriosus repair. Semin Thorac Cardiovasc Surg. 2022;34(3):1003-1009. PMID: 34087373. https://doi.org/10.1053/j.semtcvs.2021.05.013
  114. Sakaue T., Nakaoka H., Shikata F., Aono J., Kurata M., Uetani T., Hamaguchi M., Kojima A., Uchita S., Yasugi T., Higashi H., Suzuki J., Ikeda S., Higaki J., Higashiyama S., Izutani H. Biochemical and histological evidence of deteriorated bioprosthetic valve leaflets: the accumulation of fibrinogen and plasminogen. Biol Open. 2018;7(8):bio034009. PMID: 30089611; PMCID: PMC6124578. https://doi.org/10.1242/bio.034009
  115. Moore L.B., Kyriakides T.R. Molecular characterization of macrophage-biomaterial interactions. Adv Exp Med Biol. 2015;865:109-22. PMID: 26306446; PMCID: PMC4643849. https://doi.org/10.1007/978-3-319-18603-0_7
  116. Canton M., Sánchez-Rodríguez R., Spera I., Venegas F.C., Favia M., Viola A., Castegna A. Reactive oxygen species in macrophages: sources and targets. Front Immunol. 2021;12:734229. PMID: 34659222; PMCID: PMC8515906. https://doi.org/10.3389/fimmu.2021.734229
  117. 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. J Am Heart Assoc. 2020;9(19):e018506. PMID: 32954917; PMCID: PMC7792365. https://doi.org/10.1161/JAHA.120.018506
  118. Dalgliesh A.J., Parvizi M., Lopera-Higuita M., Shklover J., Griffiths L.G. Graft-specific immune tolerance is determined by residual antigenicity of xenogeneic extracellular matrix scaffolds. Acta Biomater. 2018;79:253-264. PMID: 30130615; PMCID: PMC6349227. https://doi.org/10.1016/j.actbio.2018.08.016
  119. Lee W., Long C., Ramsoondar J., Ayares D., Cooper D.K., Manji R.A., Hara H. Human antibody recognition of xenogeneic antigens (NeuGc and Gal) on porcine heart valves: could genetically modified pig heart valves reduce structural valve deterioration? Xenotransplantation. 2016;23(5):370-80. PMID: 27511593. https://doi.org/10.1111/xen.12254
  120. Wang L., Nancollas G.H. Calcium orthophosphates: crystallization and dissolution. Chem Rev. 2008;108(11):4628-69. PMID: 18816145; PMCID: PMC2743557. https://doi.org/10.1021/cr0782574
  121. Levy R.J., Wolfrum J., Schoen F.J., Hawley M.A., Lund S.A., Langer R. Inhibition of calcification of bioprosthetic heart valves by local controlled-release diphosphonate. Science. 1985;228(4696):190-2. PMID: 3919445. https://doi.org/10.1126/science.3919445
  122. Dvir D., Bourguignon T., Otto C.M., Hahn R.T., Rosenhek R., Webb J.G., Treede H., Sarano M.E., Feldman T., Wijeysundera H.C., Topilsky Y., Aupart M., Reardon M.J., Mackensen G.B., Szeto W.Y., Kornowski R., Gammie J.S., Yoganathan A.P., Arbel Y., Borger M.A., Simonato M., Reisman M., Makkar R.R., Abizaid A., McCabe J.M., Dahle G., Aldea G.S., Leipsic J., Pibarot P., Moat N.E., Mack M.J., Kappetein A.P., Leon M.B.; VIVID (Valve in Valve International Data) Investigators. Standardized definition of structural valve degeneration for surgical and transcatheter bioprosthetic aortic valves. Circulation. 2018;137(4):388-399. PMID: 29358344. https://doi.org/10.1161/CIRCULATIONAHA.117.030729