·
REVIEW
·

Experimental and computational models for tissue-engineered heart valves: a narrative review

Ge Yan1 Yuqi Liu1 Minghui Xie1 Jiawei Shi1 Weihua Qiao1* Nianguo Dong1*
Show Less
1 Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China
Submitted: 30 August 2021 | Revised: 26 November 2021 | Accepted: 3 December 2021 | Published: 28 December 2021
Copyright © 2021 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution–NonCommercial–ShareAlike 4.0 License.
Abstract

Valvular heart disease is currently a common problem which causes high morbidity and mortality worldwide. Prosthetic valve replacements are widely needed to correct narrowing or backflow through the valvular orifice. Compared to mechanical valves and biological valves, tissue-engineered heart valves can be an ideal substitute because they have a low risk of thromboembolism and calcification, and the potential for remodelling, regeneration, and growth. In order to test the performance of these heart valves, various animal models and other models are needed to optimise the structure and function of tissue-engineered heart valves, which may provide a potential mechanism responsible for substantial enhancement in tissue-engineered heart valves. Choosing the appropriate model for evaluating the performance of the tissue-engineered valve is important, as different models have their own advantages and disadvantages. In this review, we summarise the current state-of-the-art animal models, bioreactors, and computational simulation models with the aim of creating more strategies for better development of tissue-engineered heart valves. This review provides an overview of major factors that influence the selection and design of a model for tissue-engineered heart valve. Continued efforts in improving and testing models for valve regeneration remain crucial in basic science and translational researches. Future research should focus on finding the right animal model and developing better in vitro testing systems for tissue-engineered heart valve.

Keywords
animal model ; bioreactor ; computational modelling ; tissue-engineered heart valve
References

Below is the content of the Citations in the paper which has been de-formatted, however, the content stays consistent with the original.

1. Fioretta, E. S.; Motta, S. E.; Lintas, V.; Loerakker, S.; Parker, K. K.; Baaijens, F. P. T.; Falk, V.; Hoerstrup, S. P.; Emmert, M. Y. Next-generation tissue-engineered heart valves with repair, remodelling and regeneration capacity. Nat Rev Cardiol. 2021, 18, 92-116.  
2. Eoh, J. H.; Shen, N.; Burke, J. A.; Hinderer, S.; Xia, Z.; Schenke-Layland, K.; Gerecht, S. Enhanced elastin synthesis and maturation in human vascular smooth muscle tissue derived from induced-pluripotent stem cells. Acta Biomater. 2017, 52, 49-59.  
3. Henaine, R.; Roubertie, F.; Vergnat, M.; Ninet, J. Valve replacement in children: a challenge for a whole life. Arch Cardiovasc Dis. 2012, 105, 517-528.  
4. Kaneko, T.; Cohn, L. H.; Aranki, S. F. Tissue valve is the preferred option for patients aged 60 and older. Circulation. 2013, 128, 1365-1371.  
5. Emmert, M. Y.; Hoerstrup, S. P. Challenges in translating tissue engineered heart valves into clinical practice. Eur Heart J. 2017, 38, 619-621.  
6. Zhang, B. L.; Bianco, R. W.; Schoen, F. J. Preclinical assessment of cardiac valve substitutes: current status and considerations for engineered tissue heart valves. Front Cardiovasc Med. 2019, 6, 72.  
7. Chester, A. H.; Grande-Allen, K. J. Which biological properties of heart valves are relevant to tissue engineering? Front Cardiovasc Med. 2020, 7, 63.  
8. Quint, C.; Kondo, Y.; Manson, R. J.; Lawson, J. H.; Dardik, A.; Niklason, L. E. Decellularized tissue-engineered blood vessel as an arterial conduit. Proc Natl Acad Sci U S A. 2011, 108, 9214-9219.  
9. Dahl, S. L.; Kypson, A. P.; Lawson, J. H.; Blum, J. L.; Strader, J. T.; Li, Y.; Manson, R. J.; Tente, W. E.; DiBernardo, L.; Hensley, M. T.; Carter, R.; Williams, T. P.; Prichard, H. L.; Dey, M. S.; Begelman, K. G.; Niklason, L. E. Readily available tissue-engineered vascular grafts. Sci Transl Med. 2011, 3, 68ra69.  
10. Majid, Q. A.; Fricker, A. T. R.; Gregory, D. A.; Davidenko, N.; Hernandez Cruz, O.; Jabbour, R. J.; Owen, T. J.; Basnett, P.; Lukasiewicz, B.; Stevens, M.; Best, S.; Cameron, R.; Sinha, S.; Harding, S. E.; Roy, I. Natural biomaterials for cardiac tissue engineering: a highly biocompatible solution. Front Cardiovasc Med. 2020, 7, 554597.  
11. Xue, Y.; Sant, V.; Phillippi, J.; Sant, S. Biodegradable and biomimetic elastomeric scaffolds for tissue-engineered heart valves. Acta Biomater. 2017, 48, 2-19.  
12. Mirani, B.; Parvin Nejad, S.; Simmons, C. A. Recent progress toward clinical translation of tissue-engineered heart valves. Can J Cardiol. 2021, 37, 1064-1077.  
13. Hayashida, K.; Kanda, K.; Yaku, H.; Ando, J.; Nakayama, Y. Development of an in vivo tissue-engineered, autologous heart valve (the biovalve): preparation of a prototype model. J Thorac Cardiovasc Surg. 2007, 134, 152-159.  
14. Yamanami, M.; Yahata, Y.; Uechi, M.; Fujiwara, M.; Ishibashi-Ueda, H.; Kanda, K.; Watanabe, T.; Tajikawa, T.; Ohba, K.; Yaku, H.; Nakayama, Y. Development of a completely autologous valved conduit with the sinus of Valsalva using in-body tissue architecture technology: a pilot study in pulmonary valve replacement in a beagle model. Circulation. 2010, 122, S100-106.  
15. Motta, S. E.; Lintas, V.; Fioretta, E. S.; Dijkman, P. E.; Putti, M.; Caliskan, E.; Rodriguez Cetina Biefer, H.; Lipiski, M.; Sauer, M.; Cesarovic, N.; Hoerstrup, S. P.; Emmert, M. Y. Human cell-derived tissue-engineered heart valve with integrated Valsalva sinuses: towards native-like transcatheter pulmonary valve replacements. NPJ Regen Med. 2019, 4, 14.  
16. Schmitt, B.; Spriestersbach, H.; D, O. H. I.; Radtke, T.; Bartosch, M.; Peters, H.; Sigler, M.; Frese, L.; Dijkman, P. E.; Baaijens, F. P.; Hoerstrup, S. P.; Berger, F. Percutaneous pulmonary valve replacement using completely tissue-engineered off-the-shelf heart valves: six-month in vivo functionality and matrix remodelling in sheep. EuroIntervention. 2016, 12, 62-70.  
17. Capulli, A. K.; Emmert, M. Y.; Pasqualini, F. S.; Kehl, D.; Caliskan, E.; Lind, J. U.; Sheehy, S. P.; Park, S. J.; Ahn, S.; Weber, B.; Goss, J. A.; Hoerstrup, S. P.; Parker, K. K. JetValve: Rapid manufacturing of biohybrid scaffolds for biomimetic heart valve replacement. Biomaterials. 2017, 133, 229-241.  
18. 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.  
19. Lovekamp, J. J.; Simionescu, D. T.; Mercuri, J. J.; Zubiate, B.; Sacks, M. S.; Vyavahare, N. R. Stability and function of glycosaminoglycans in porcine bioprosthetic heart valves. Biomaterials. 2006, 27, 1507-1518.  
20. Jana, S.; Franchi, F.; Lerman, A. Trilayered tissue structure with leaflet-like orientations developed through in vivo tissue engineering. Biomed Mater. 2019, 15, 015004.  
21. Soares, A. L.; Oomens, C. W.; Baaijens, F. P. A computational model to describe the collagen orientation in statically cultured engineered tissues. Comput Methods Biomech Biomed Engin. 2014, 17, 251-262.  
22. Emmert, M. Y.; Schmitt, B. A.; Loerakker, S.; Sanders, B.; Spriestersbach, H.; Fioretta, E. S.; Bruder, L.; Brakmann, K.; Motta, S. E.; Lintas, V.; Dijkman, P. E.; Frese, L.; Berger, F.; Baaijens, F. P. T.; Hoerstrup, S. P. Computational modeling guides tissue-engineered heart valve design for long-term in vivo performance in a translational sheep model. Sci Transl Med. 2018, 10, eaan4587.  
23. Flanagan, T. C.; Sachweh, J. S.; Frese, J.; Schnöring, H.; Gronloh, N.; Koch, S.; Tolba, R. H.; Schmitz-Rode, T.; Jockenhoevel, S. In vivo remodeling and structural characterization of fibrin-based tissue-engineered heart valves in the adult sheep model. Tissue Eng Part A. 2009, 15, 2965-2976.  
24. Wu, H.; Xu, Z. W.; Liu, X. M.; Gong, D.; Wan, J. Y.; Xu, X. F.; Zhou, Z. F.; Li, W. B. An in vivo model of in situ implantation using pulmonary valved conduit in large animals under off-pump condition. Chin Med J (Engl). 2013, 126, 4540-4544.  
25. Zakko, J.; Blum, K. M.; Drews, J. D.; Wu, Y. L.; Hatoum, H.; Russell, M.; Gooden, S.; Heitkemper, M.; Conroy, O.; Kelly, J.; Carey, S.; Sacks, M.; Texter, K.; Ragsdale, E.; Strainic, J.; Bocks, M.; Wang, Y.; Dasi, L. P.; Armstrong, A. K.; Breuer, C. Development of tissue engineered heart valves for percutaneous transcatheter delivery in a fetal ovine model. JACC Basic Transl Sci. 2020, 5, 815-828.  
26. Coyan, G. N.; D’Amore, A.; Matsumura, Y.; Pedersen, D. D.; Luketich, S. K.; Shanov, V.; Katz, W. E.; David, T. E.; Wagner, W. R.; Badhwar, V. In vivo functional assessment of a novel degradable metal and elastomeric scaffold-based tissue engineered heart valve. J Thorac Cardiovasc Surg. 2019, 157, 1809-1816.  
27. Schlegel, F.; Salameh, A.; Oelmann, K.; Halling, M.; Dhein, S.; Mohr, F. W.; Dohmen, P. M. Injectable tissue engineered pulmonary heart valve implantation into the pig model: A feasibility study. Med Sci Monit Basic Res. 2015, 21, 135-140.  
28. Bianco, R. W.; St Cyr, J. A.; Schneider, J. R.; Rasmussen, T. M.; Clack, R. M.; Shim, H. S.; Sandstad, J.; Rysavy, J.; Foker, J. E. Canine model for long-term evaluation of prosthetic mitral valves. J Surg Res. 1986, 41, 134-140.  
29. Ye, X.; Bhushan, B.; Zhou, M.; Lei, W. The surface microstructure of cusps and leaflets in rabbit and mouse heart valves. Beilstein J Nanotechnol. 2014, 5, 622-629.  
30. Weber, B.; Dijkman, P. E.; Scherman, J.; Sanders, B.; Emmert, M. Y.; Grünenfelder, J.; Verbeek, R.; Bracher, M.; Black, M.; Franz, T.; Kortsmit, J.; Modregger, P.; Peter, S.; Stampanoni, M.; Robert, J.; Kehl, D.; van Doeselaar, M.; Schweiger, M.; Brokopp, C. E.; Wälchli, T.; Falk, V.; Zilla, P.; Driessen-Mol, A.; Baaijens, F. P.; Hoerstrup, S. P. Off-the-shelf human decellularized tissue-engineered heart valves in a non-human primate model. Biomaterials. 2013, 34, 7269-7280.  
31. Smith, M. R.; Wood, W. B., Jr. An experimental analysis of the curative action of penicillin in acute bacterial infections. III. The effect of suppuration upon the antibacterial action of the drug. J Exp Med. 1956, 103, 509-522.  
32. Kim, M. S.; Jeong, S.; Lim, H. G.; Kim, Y. J. Differences in xenoreactive immune response and patterns of calcification of porcine and bovine tissues in α-Gal knock-out and wild-type mouse implantation models. Eur J Cardiothorac Surg. 2015, 48, 392-399.  
33. Christ, T.; Dohmen, P. M.; Holinski, S.; Schönau, M.; Heinze, G.; Konertz, W. Suitability of the rat subdermal model for tissue engineering of heart valves. Med Sci Monit Basic Res. 2014, 20, 194-199.  
34. Assmann, A.; Delfs, C.; Munakata, H.; Schiffer, F.; Horstkötter, K.; Huynh, K.; Barth, M.; Stoldt, V. R.; Kamiya, H.; Boeken, U.; Lichtenberg, A.; Akhyari, P. Acceleration of autologous in vivo recellularization of decellularized aortic conduits by fibronectin surface coating. Biomaterials. 2013, 34, 6015-6026.  
35. Rashid, S. T.; Salacinski, H. J.; Hamilton, G.; Seifalian, A. M. The use of animal models in developing the discipline of cardiovascular tissue engineering: a review. Biomaterials. 2004, 25, 1627-1637.  
36. Driessen-Mol, A.; Emmert, M. Y.; Dijkman, P. E.; Frese, L.; Sanders, B.; Weber, B.; Cesarovic, N.; Sidler, M.; Leenders, J.; Jenni, R.; Grünenfelder, J.; Falk, V.; Baaijens, F. P. T.; Hoerstrup, S. P. Transcatheter implantation of homologous “off-the-shelf” tissue-engineered heart valves with self-repair capacity: long-term functionality and rapid in vivo remodeling in sheep. J Am Coll Cardiol. 2014, 63, 1320-1329.  
37. Shinoka, T.; Ma, P. X.; Shum-Tim, D.; Breuer, C. K.; Cusick, R. A.; Zund, G.; Langer, R.; Vacanti, J. P.; Mayer, J. E., Jr. Tissue-engineered heart valves. Autologous valve leaflet replacement study in a lamb model. Circulation. 1996, 94, II164-168.  
38. Schroeder, F.; Polzer, S.; Slažanský, M.; Man, V.; Skácel, P. Predictive capabilities of various constitutive models for arterial tissue. J Mech Behav Biomed Mater. 2018, 78, 369-380.  
39. Swindle, M. M.; Makin, A.; Herron, A. J.; Clubb, F. J., Jr.; Frazier, K. S. Swine as models in biomedical research and toxicology testing. Vet Pathol. 2012, 49, 344-356.  
40. Grehan, J. F.; Hilbert, S. L.; Ferrans, V. J.; Droel, J. S.; Salerno, C. T.; Bianco, R. W. Development and evaluation of a swine model to assess the preclinical safety of mechanical heart valves. J Heart Valve Dis. 2000, 9, 710-719; discussion 719-720.  
41. Canty, J. M., Jr.; Suzuki, G.; Banas, M. D.; Verheyen, F.; Borgers, M.; Fallavollita, J. A. Hibernating myocardium: chronically adapted to ischemia but vulnerable to sudden death. Circ Res. 2004, 94, 1142-1149.  
42. Gallo, M.; Poser, H.; Bottio, T.; Bonetti, A.; Franci, P.; Naso, F.; Buratto, E.; Zanella, F.; Perona, G.; Dal Lin, C.; Bianco, R.; Spina, M.; Busetto, R.; Marchini, M.; Ortolani, F.; Iop, L.; Gerosa, G. The Vietnamese pig as a translational animal model to evaluate tissue engineered heart valves: promising early experience. Int J Artif Organs. 2017, 40, 142-149.  
43. Gallo, M.; Bianco, R.; Bottio, T.; Naso, F.; Franci, P.; Zanella, F.; Perona, G.; Busetto, R.; Spina, M.; Gandaglia, A.; Gerosa, G. Tissue-engineered heart valves: intra-operative protocol. J Cardiovasc Transl Res. 2013, 6, 660-661.  
44. Gallo, M.; Naso, F.; Poser, H.; Rossi, A.; Franci, P.; Bianco, R.; Micciolo, M.; Zanella, F.; Cucchini, U.; Aresu, L.; Buratto, E.; Busetto, R.; Spina, M.; Gandaglia, A.; Gerosa, G. Physiological performance of a detergent decellularized heart valve implanted for 15 months in Vietnamese pigs: surgical procedure, follow-up, and explant inspection. Artif Organs. 2012, 36, E138-150.  
45. Boudjemline, Y.; Agnoletti, G.; Bonnet, D.; Behr, L.; Borenstein, N.; Sidi, D.; Bonhoeffer, P. Steps toward the percutaneous replacement of atrioventricular valves: an experimental study. J Am Coll Cardiol. 2005, 46, 360-365.  
46. Dewey, T. M.; Walther, T.; Doss, M.; Brown, D.; Ryan, W. H.; Svensson, L.; Mihaljevic, T.; Hambrecht, R.; Schuler, G.; Wimmer-Greinecker, G.; Mohr, F. W.; Mack, M. J. Transapical aortic valve implantation: an animal feasibility study. Ann Thorac Surg. 2006, 82, 110-116.  
47. Lutter, G.; Kuklinski, D.; Berg, G.; Von Samson, P.; Martin, J.; Handke, M.; Uhrmeister, P.; Beyersdorf, F. Percutaneous aortic valve replacement: an experimental study. I. Studies on implantation. J Thorac Cardiovasc Surg. 2002, 123, 768-776.  
48. Walther, T.; Dewey, T.; Wimmer-Greinecker, G.; Doss, M.; Hambrecht, R.; Schuler, G.; Mohr, F. W.; Mack, M. Transapical approach for sutureless stent-fixed aortic valve implantation: experimental results. Eur J Cardiothorac Surg. 2006, 29, 703-708.  
49. Kokozidou, M.; Katsargyris, A.; Verhoeven, E. L. G.; Schulze-Tanzil, G. Vascular access animal models used in research. Ann Anat. 2019, 225, 65-75.  
50. Camacho, P.; Fan, H.; Liu, Z.; He, J. Q. Large mammalian animal models of heart disease. J Cardiovasc Dev Dis. 2016, 3, 30.  
51. Iwai, S.; Torikai, K.; Coppin, C. M.; Sawa, Y. Minimally immunogenic decellularized porcine valve provides in situ recellularization as a stentless bioprosthetic valve. J Artif Organs. 2007, 10, 29-35.  
52. Yang, H.; Shao, N.; Holmström, A.; Zhao, X.; Chour, T.; Chen, H.; Itzhaki, I.; Wu, H.; Ameen, M.; Cunningham, N. J.; Tu, C.; Zhao, M. T.; Tarantal, A. F.; Abilez, O. J.; Wu, J. C. Transcriptome analysis of non-human primate-induced pluripotent stem cell-derived cardiomyocytes in 2D monolayer culture vs. 3D engineered heart tissue. Cardiovasc Res. 2021, 117, 2125-2136.  
53. Rahman, M. A.; Robert-Guroff, M. Accelerating HIV vaccine development using non-human primate models. Expert Rev Vaccines. 2019, 18, 61-73.  
54. Brok, H. P.; Bauer, J.; Jonker, M.; Blezer, E.; Amor, S.; Bontrop, R. E.; Laman, J. D.; t Hart, B. A. Non-human primate models of multiple sclerosis. Immunol Rev. 2001, 183, 173-185.  
55. Lu, T.; Yang, B.; Wang, R.; Qin, C. Xenotransplantation: current status in preclinical research. Front Immunol. 2019, 10, 3060.  
56. Anderson, J. M.; Rodriguez, A.; Chang, D. T. Foreign body reaction to biomaterials. Semin Immunol. 2008, 20, 86-100.  
57. Raasch, M.; Rennert, K.; Jahn, T.; Peters, S.; Henkel, T.; Huber, O.; Schulz, I.; Becker, H.; Lorkowski, S.; Funke, H.; Mosig, A. Microfluidically supported biochip design for culture of endothelial cell layers with improved perfusion conditions. Biofabrication. 2015, 7, 015013.  
58. Rath, S.; Salinas, M.; Villegas, A. G.; Ramaswamy, S. Differentiation and distribution of marrow stem cells in flex-flow environments demonstrate support of the valvular phenotype. PLoS One. 2015, 10, e0141802.  
59. Flanagan, T. C.; Cornelissen, C.; Koch, S.; Tschoeke, B.; Sachweh, J. S.; Schmitz-Rode, T.; Jockenhoevel, S. The in vitro development of autologous fibrin-based tissue-engineered heart valves through optimised dynamic conditioning. Biomaterials. 2007, 28, 3388-3397.  
60. Deb, N.; Ali, M. S.; Mathews, A.; Chang, Y. W.; Lacerda, C. M. Shear type and magnitude affect aortic valve endothelial cell morphology, orientation, and differentiation. Exp Biol Med (Maywood). 2021, 246, 2278-2289.  
61. Li, A.; Tan, L.; Zhang, S.; Tao, J.; Wang, Z.; Wei, D. Low shear stress-induced endothelial mesenchymal transformation via the down-regulation of TET2. Biochem Biophys Res Commun. 2021, 545, 20-26.  
62. Bazan, O.; Simbara, M. M. O.; Ortiz, J. P.; Malmonge, S. M.; Andrade, A.; Yanagihara, J. I. In vitro hydrodynamic evaluation of a scaffold for heart valve tissue engineering. Artif Organs. 2019, 43, 195-198.  
63. Tefft, B. J.; Choe, J. A.; Young, M. D.; Hennessy, R. S.; Morse, D. W.; Bouchard, J. A.; Hedberg, H. J.; Consiglio, J. F.; Dragomir-Daescu, D.; Simari, R. D.; Lerman, A. Cardiac valve bioreactor for physiological conditioning and hydrodynamic performance assessment. Cardiovasc Eng Technol. 2019, 10, 80-94.  
64. Kim, J.; Lee, Y.; Choi, S.; Ha, H. Pulsatile flow pump based on an iterative controlled piston pump actuator as an in-vitro cardiovascular flow model. Med Eng Phys. 2020, 77, 118-124.  
65. Qian, T.; Gil, D. A.; Contreras Guzman, E.; Gastfriend, B. D.; Tweed, K. E.; Palecek, S. P.; Skala, M. C. Adaptable pulsatile flow generated from stem cell-derived cardiomyocytes using quantitative imaging-based signal transduction. Lab Chip. 2020, 20, 3744-3756.  
66. Posmantur, R.; Hayes, R. L.; Dixon, C. E.; Taft, W. C. Neurofilament 68 and neurofilament 200 protein levels decrease after traumatic brain injury. J Neurotrauma. 1994, 11, 533-545.  
67. Hildebrand, D. K.; Wu, Z. J.; Mayer, J. E., Jr.; Sacks, M. S. Design and hydrodynamic evaluation of a novel pulsatile bioreactor for biologically active heart valves. Ann Biomed Eng. 2004, 32, 1039-1049.  
68. Gandaglia, A.; Bagno, A.; Naso, F.; Spina, M.; Gerosa, G. Cells, scaffolds and bioreactors for tissue-engineered heart valves: a journey from basic concepts to contemporary developmental innovations. Eur J Cardiothorac Surg. 2011, 39, 523-531.  
69. Ramaswamy, S.; Boronyak, S. M.; Le, T.; Holmes, A.; Sotiropoulos, F.; Sacks, M. S. A novel bioreactor for mechanobiological studies of engineered heart valve tissue formation under pulmonary arterial physiological flow conditions. J Biomech Eng. 2014, 136, 121009.  
70. Nguemgo Kouam, P.; Bühler, H.; Hero, T.; Adamietz, I. A. The increased adhesion of tumor cells to endothelial cells after irradiation can be reduced by FAK-inhibition. Radiat Oncol. 2019, 14, 25.  
71. Hampel, U.; Garreis, F.; Burgemeister, F.; Eßel, N.; Paulsen, F. Effect of intermittent shear stress on corneal epithelial cells using an in vitro flow culture model. Ocul Surf. 2018, 16, 341-351.  
72. Helle, E.; Ampuja, M.; Antola, L.; Kivelä, R. Flow-induced transcriptomic remodeling of endothelial cells derived from human induced pluripotent stem cells. Front Physiol. 2020, 11, 591450.  
73. Moon du, G.; Christ, G.; Stitzel, J. D.; Atala, A.; Yoo, J. J. Cyclic mechanical preconditioning improves engineered muscle contraction. Tissue Eng Part A. 2008, 14, 473-482.  
74. Sun, L.; Qu, L.; Zhu, R.; Li, H.; Xue, Y.; Liu, X.; Fan, J.; Fan, H. Effects of mechanical stretch on cell proliferation and matrix formation of mesenchymal stem cell and anterior cruciate ligament fibroblast. Stem Cells Int. 2016, 2016, 9842075.  
75. Ku, C. H.; Johnson, P. H.; Batten, P.; Sarathchandra, P.; Chambers, R. C.; Taylor, P. M.; Yacoub, M. H.; Chester, A. H. Collagen synthesis by mesenchymal stem cells and aortic valve interstitial cells in response to mechanical stretch. Cardiovasc Res. 2006, 71, 548-556.  
76. Syedain, Z. H.; Tranquillo, R. T. Controlled cyclic stretch bioreactor for tissue-engineered heart valves. Biomaterials. 2009, 30, 4078-4084.  
77. Engelmayr, G. C., Jr.; Rabkin, E.; Sutherland, F. W.; Schoen, F. J.; Mayer, J. E., Jr.; Sacks, M. S. The independent role of cyclic flexure in the early in vitro development of an engineered heart valve tissue. Biomaterials. 2005, 26, 175-187.  
78. Engelmayr, G. C., Jr.; Hildebrand, D. K.; Sutherland, F. W.; Mayer, J. E., Jr.; Sacks, M. S. A novel bioreactor for the dynamic flexural stimulation of tissue engineered heart valve biomaterials. Biomaterials. 2003, 24, 2523-2532.  
79. Kutikhin, A. G.; Sinitsky, M. Y.; Yuzhalin, A. E.; Velikanova, E. A. Shear stress: an essential driver of endothelial progenitor cells. J Mol Cell Cardiol. 2018, 118, 46-69.  
80. Yang, Z.; Xia, W. H.; Zhang, Y. Y.; Xu, S. Y.; Liu, X.; Zhang, X. Y.; Yu, B. B.; Qiu, Y. X.; Tao, J. Shear stress-induced activation of Tie2-dependent signaling pathway enhances reendothelialization capacity of early endothelial progenitor cells. J Mol Cell Cardiol. 2012, 52, 1155-1163.  
81. Campinho, P.; Vilfan, A.; Vermot, J. Blood flow forces in shaping the vascular system: a focus on endothelial cell behavior. Front Physiol. 2020, 11, 552.  
82. da Silva, R. A.; Fernandes, C.; Feltran, G. D. S.; Gomes, A. M.; de Camargo Andrade, A. F.; Andia, D. C.; Peppelenbosch, M. P.; Zambuzzi, W. F. Laminar shear stress-provoked cytoskeletal changes are mediated by epigenetic reprogramming of TIMP1 in human primary smooth muscle cells. J Cell Physiol. 2019, 234, 6382-6396.  
83. Gonzalez, B. A.; Perez-Nevarez, M.; Mirza, A.; Perez, M. G.; Lin, Y. M.; Hsu, C. D.; Caobi, A.; Raymond, A.; Gomez Hernandez, M. E.; Fernandez-Lima, F.; George, F.; Ramaswamy, S. Physiologically relevant fluid-induced oscillatory shear stress stimulation of mesenchymal stem cells enhances the engineered valve matrix phenotype. Front Cardiovasc Med. 2020, 7, 69.  
84. Li, J.; He, Y.; Bu, H.; Wang, M.; Yu, J.; Li, L.; Li, H.; Zhang, X.; Cui, X.; Cheng, M. Oscillating shear stress mediates mesenchymal transdifferentiation of EPCs by the Kir2.1 channel. Heart Vessels. 2020, 35, 1473-1482.  
85. Gao, Y.; Cui, X.; Wang, M.; Zhang, Y.; He, Y.; Li, L.; Li, H.; Zhang, X.; Cheng, M. Oscillatory shear stress induces the transition of EPCs into mesenchymal cells through ROS/PKCζ/p53 pathway. Life Sci. 2020, 253, 117728.  
86. Converse, G. L.; Buse, E. E.; Neill, K. R.; McFall, C. R.; Lewis, H. N.; VeDepo, M. C.; Quinn, R. W.; Hopkins, R. A. Design and efficacy of a single-use bioreactor for heart valve tissue engineering. J Biomed Mater Res B Appl Biomater. 2017, 105, 249-259.  
87. Jockenhoevel, S.; Zund, G.; Hoerstrup, S. P.; Schnell, A.; Turina, M. Cardiovascular tissue engineering: a new laminar flow chamber for in vitro improvement of mechanical tissue properties. ASAIO J. 2002, 48, 8-11.  
88. Engelmayr, G. C., Jr.; Sales, V. L.; Mayer, J. E., Jr.; Sacks, M. S. Cyclic flexure and laminar flow synergistically accelerate mesenchymal stem cell-mediated engineered tissue formation: Implications for engineered heart valve tissues. Biomaterials. 2006, 27, 6083-6095.  
89. Ramaswamy, S.; Gottlieb, D.; Engelmayr, G. C., Jr.; Aikawa, E.; Schmidt, D. E.; Gaitan-Leon, D. M.; Sales, V. L.; Mayer, J. E., Jr.; Sacks, M. S. The role of organ level conditioning on the promotion of engineered heart valve tissue development in vitro using mesenchymal stem cells. Biomaterials. 2010, 31, 1114-1125.  
90. Mongkoldhumrongkul, N.; Latif, N.; Yacoub, M. H.; Chester, A. H. Effect of side-specific valvular shear stress on the content of extracellular matrix in aortic valves. Cardiovasc Eng Technol. 2018, 9, 151-157.  
91. Engelmayr, G. C., Jr.; Soletti, L.; Vigmostad, S. C.; Budilarto, S. G.; Federspiel, W. J.; Chandran, K. B.; Vorp, D. A.; Sacks, M. S. A novel flex-stretch-flow bioreactor for the study of engineered heart valve tissue mechanobiology. Ann Biomed Eng. 2008, 36, 700-712.  
92. Vozzi, F.; Bianchi, F.; Ahluwalia, A.; Domenici, C. Hydrostatic pressure and shear stress affect endothelin-1 and nitric oxide release by endothelial cells in bioreactors. Biotechnol J. 2014, 9, 146-154.  
93. VeDepo, M. C.; Buse, E. E.; Paul, A.; Converse, G. L.; Hopkins, R. A. Non-physiologic bioreactor processing conditions for heart valve tissue engineering. Cardiovasc Eng Technol. 2019, 10, 628-637.  
94. Hutmacher, D. W.; Singh, H. Computational fluid dynamics for improved bioreactor design and 3D culture. Trends Biotechnol. 2008, 26, 166-172.  
95. Williams, A.; Nasim, S.; Salinas, M.; Moshkforoush, A.; Tsoukias, N.; Ramaswamy, S. A “sweet-spot” for fluid-induced oscillations in the conditioning of stem cell-based engineered heart valve tissues. J Biomech. 2017, 65, 40-48.  
96. Salinas, M.; Ramaswamy, S. Computational simulations predict a key role for oscillatory fluid shear stress in de novo valvular tissue formation. J Biomech. 2014, 47, 3517-3523.  
97. Lichtenberg, A.; Tudorache, I.; Cebotari, S.; Suprunov, M.; Tudorache, G.; Goerler, H.; Park, J. K.; Hilfiker-Kleiner, D.; Ringes-Lichtenberg, S.; Karck, M.; Brandes, G.; Hilfiker, A.; Haverich, A. Preclinical testing of tissue-engineered heart valves re-endothelialized under simulated physiological conditions. Circulation. 2006, 114, I559-565.  
98. Lichtenberg, A.; Tudorache, I.; Cebotari, S.; Ringes-Lichtenberg, S.; Sturz, G.; Hoeffler, K.; Hurscheler, C.; Brandes, G.; Hilfiker, A.; Haverich, A. In vitro re-endothelialization of detergent decellularized heart valves under simulated physiological dynamic conditions. Biomaterials. 2006, 27, 4221-4229.  
99. Santoro, R.; Venkateswaran, S.; Amadeo, F.; Zhang, R.; Brioschi, M.; Callanan, A.; Agrifoglio, M.; Banfi, C.; Bradley, M.; Pesce, M. Acrylate-based materials for heart valve scaffold engineering. Biomater Sci. 2017, 6, 154-167.  
100. Best, C. A.; Szafron, J. M.; Rocco, K. A.; Zbinden, J.; Dean, E. W.; Maxfield, M. W.; Kurobe, H.; Tara, S.; Bagi, P. S.; Udelsman, B. V.; Khosravi, R.; Yi, T.; Shinoka, T.; Humphrey, J. D.; Breuer, C. K. Differential outcomes of venous and arterial tissue engineered vascular grafts highlight the importance of coupling long-term implantation studies with computational modeling. Acta Biomater. 2019, 94, 183-194.  
101. Hsu, M. C.; Kamensky, D.; Xu, F.; Kiendl, J.; Wang, C.; Wu, M. C.; Mineroff, J.; Reali, A.; Bazilevs, Y.; Sacks, M. S. Dynamic and fluid-structure interaction simulations of bioprosthetic heart valves using parametric design with T-splines and Fung-type material models. Comput Mech. 2015, 55, 1211-1225.  
102. Martin, C.; Sun, W. Simulation of long-term fatigue damage in bioprosthetic heart valves: effects of leaflet and stent elastic properties. Biomech Model Mechanobiol. 2014, 13, 759-770.  
103. Szafron, J. M.; Ramachandra, A. B.; Breuer, C. K.; Marsden, A. L.; Humphrey, J. D. Optimization of tissue-engineered vascular graft design using computational modeling. Tissue Eng Part C Methods. 2019, 25, 561-570.  
104. Sulejmani, F.; Caballero, A.; Martin, C.; Pham, T.; Sun, W. Evaluation of transcatheter heart valve biomaterials: Computational modeling using bovine and porcine pericardium. J Mech Behav Biomed Mater. 2019, 97, 159-170.  
105. Zakerzadeh, R.; Hsu, M. C.; Sacks, M. S. Computational methods for the aortic heart valve and its replacements. Expert Rev Med Devices. 2017, 14, 849-866.  
106. Abbasi, M.; Barakat, M. S.; Vahidkhah, K.; Azadani, A. N. Characterization of three-dimensional anisotropic heart valve tissue mechanical properties using inverse finite element analysis. J Mech Behav Biomed Mater. 2016, 62, 33-44.  
107. Fernández-Ruiz, I. Computer modelling to personalize bioengineered heart valves. Nat Rev Cardiol. 2018, 15, 440-441.  
108. Butcher, J. T. The root problem of heart valve engineering. Sci Transl Med. 2018, 10, eaat5850.  
109. Simmons, C. A. Taking bioengineered heart valves from faulty to functional. Nature. 2018, 559, 42-43.  
110. Loureiro-Ga, M.; Veiga, C.; Fdez-Manin, G.; Jimenez, V. A.; Calvo-Iglesias, F.; Iñiguez, A. A biomechanical model of the pathological aortic valve: simulation of aortic stenosis. Comput Methods Biomech Biomed Engin. 2020, 23, 303-311.  
111. Conti, C. A.; Della Corte, A.; Votta, E.; Del Viscovo, L.; Bancone, C.; De Santo, L. S.; Redaelli, A. Biomechanical implications of the congenital bicuspid aortic valve: a finite element study of aortic root function from in vivo data. J Thorac Cardiovasc Surg. 2010, 140, 890-896, 896.e1-2.  
112. Arzani, A.; Mofrad, M. R. K. A strain-based finite element model for calcification progression in aortic valves. J Biomech. 2017, 65, 216-220.  
113. Rassoli, A.; Fatouraee, N.; Guidoin, R.; Zhang, Z. Comparison of tensile properties of xenopericardium from three animal species and finite element analysis for bioprosthetic heart valve tissue. Artif Organs. 2020, 44, 278-287.  
114. Vashistha, R.; Kumar, P.; Dangi, A. K.; Sharma, N.; Chhabra, D.; Shukla, P. Quest for cardiovascular interventions: precise modeling and 3D printing of heart valves. J Biol Eng. 2019, 13, 12.  
115. van der Valk, D. C.; van der Ven, C. F. T.; Blaser, M. C.; Grolman, J. M.; Wu, P. J.; Fenton, O. S.; Lee, L. H.; Tibbitt, M. W.; Andresen, J. L.; Wen, J. R.; Ha, A. H.; Buffolo, F.; van Mil, A.; Bouten, C. V. C.; Body, S. C.; Mooney, D. J.; Sluijter, J. P. G.; Aikawa, M.; Hjortnaes, J.; Langer, R.; Aikawa, E. Engineering a 3D-bioprinted model of human heart valve disease using nanoindentation-based biomechanics. Nanomaterials (Basel). 2018, 8, 296.  
116. Labrosse, M. R.; Beller, C. J.; Robicsek, F.; Thubrikar, M. J. Geometric modeling of functional trileaflet aortic valves: development and clinical applications. J Biomech. 2006, 39, 2665-2672.  
117. Marom, G.; Haj-Ali, R.; Rosenfeld, M.; Schäfers, H. J.; Raanani, E. Aortic root numeric model: correlation between intraoperative effective height and diastolic coaptation. J Thorac Cardiovasc Surg. 2013, 145, 303-304.  
118. Zhang, W.; Rossini, G.; Kamensky, D.; Bui-Thanh, T.; Sacks, M. S. Isogeometric finite element-based simulation of the aortic heart valve: Integration of neural network structural material model and structural tensor fiber architecture representations. Int J Numer Method Biomed Eng. 2021, 37, e3438.  
119. Li, Q.; Wang, J.; Tao, H.; Zhou, Q.; Chen, J.; Fu, B.; Qin, W.; Li, D.; Hou, J.; Chen, J.; Zhang, W. H. The prediction model of warfarin individual maintenance dose for patients undergoing heart valve replacement, based on the back propagation neural network. Clin Drug Investig. 2020, 40, 41-53.  
120. Obbink-Huizer, C.; Oomens, C. W.; Loerakker, S.; Foolen, J.; Bouten, C. V.; Baaijens, F. P. Computational model predicts cell orientation in response to a range of mechanical stimuli. Biomech Model Mechanobiol. 2014, 13, 227-236.  
121. Loerakker, S.; Obbink-Huizer, C.; Baaijens, F. P. A physically motivated constitutive model for cell-mediated compaction and collagen remodeling in soft tissues. Biomech Model Mechanobiol. 2014, 13, 985-1001.  
122. Ristori, T.; Bouten, C. V. C.; Baaijens, F. P. T.; Loerakker, S. Predicting and understanding collagen remodeling in human native heart valves during early development. Acta Biomater. 2018, 80, 203-216.  
123. Loerakker, S.; Ristori, T.; Baaijens, F. P. T. A computational analysis of cell-mediated compaction and collagen remodeling in tissue-engineered heart valves. J Mech Behav Biomed Mater. 2016, 58, 173-187.  
124. Soares, J. S.; T, B. L.; Sotiropoulos, F.; M, S. S. Modeling the role of oscillator flow and dynamic mechanical conditioning on dense connective tissue formation in mesenchymal stem cell-derived heart valve tissue engineering. J Med Device. 2013, 7, 0409271-0409272.  
125. Soares, J. S.; Sacks, M. S. A triphasic constrained mixture model of engineered tissue formation under in vitro dynamic mechanical conditioning. Biomech Model Mechanobiol. 2016, 15, 293-316.  
126. Sanders, B.; Loerakker, S.; Fioretta, E. S.; Bax, D. J.; Driessen-Mol, A.; Hoerstrup, S. P.; Baaijens, F. P. Improved geometry of decellularized tissue engineered heart valves to prevent leaflet retraction. Ann Biomed Eng. 2016, 44, 1061-1071.  
127. Loerakker, S.; Argento, G.; Oomens, C. W.; Baaijens, F. P. Effects of valve geometry and tissue anisotropy on the radial stretch and coaptation area of tissue-engineered heart valves. J Biomech. 2013, 46, 1792-1800.  
128. Motta, S. E.; Fioretta, E. S.; Lintas, V.; Dijkman, P. E.; Hilbe, M.; Frese, L.; Cesarovic, N.; Loerakker, S.; Baaijens, F. P. T.; Falk, V.; Hoerstrup, S. P.; Emmert, M. Y. Geometry influences inflammatory host cell response and remodeling in tissue-engineered heart valves in vivo. Sci Rep. 2020, 10, 19882.  

Conflict of interest
The authors declare they have no competing interests.
Share
Back to top