Biomechanics and Modeling of Tissue-Engineered Heart Valves

  • T. Ristori
  • A. J. van Kelle
  • F. P. T. Baaijens
  • S. LoerakkerEmail author


Heart valve tissue engineering (HVTE) is a promising technique to overcome the limitations of currently available heart valve prostheses. However, before clinical use, still several challenges need to be overcome. The functionality of the developed replacements is determined by their biomechanical properties and, ultimately, by their collagen architecture. Unfortunately, current techniques are often not able to induce a physiological tissue remodeling, which compromises the long-term functionality. Therefore, a deeper understanding of the process of tissue remodeling is required to optimize the phenomena involved via improving the current HVTE approaches. Computational simulations can help in this process, being a valuable and versatile tool to predict and understand experimental results. This chapter first describes the similarities and differences in functionality and biomechanical properties between native and tissue-engineered heart valves. Secondly, the current status of computational models for collagen remodeling is addressed and, finally, future directions and implications for HVTE are suggested.


Tissue engineering Heart valve Remodeling Collagen Stress fibers Computational Mathematical model Biomechanics 



Extracellular matrix


Heart valve tissue engineering


Stress fiber


Tissue engineering


Tissue-engineered heart valves


  1. 1.
    Yacoub MH, Takkenberg JJM. Will heart valve tissue engineering change the world? Nat Clin Pract Cardiovasc Med. 2005;2(2):60–1. Scholar
  2. 2.
    Zilla P, Brink J, Human P, Bezuidenhout D. Prosthetic heart valves: catering for the few. Biomaterials. 2008;29(4):385–406. Scholar
  3. 3.
    Hammermeister K, Sethi GK, Henderson WG, Grover FL, Oprian C, Rahimtoola SH. Outcomes 15 years after valve replacement with a mechanical versus a bioprosthetic valve: final report of the Veterans Affairs randomized trial. J Am Coll Cardiol. 2000;36(4):1152–8. Scholar
  4. 4.
    Oxenham H, Bloomfield P, Wheatley DJ. Twelve-year comparison of a Bjork-Shiley mechanical heart valve with porcine bioprostheses. N Engl J Med. 2003;324(9):573–9. Scholar
  5. 5.
    Curtil A, Pegg DE, Wilson A. Repopulation of freeze-dried porcine valves with human fibroblasts and endothelial cells. J Heart Valve Dis. 1997;6(3):296–306.PubMedGoogle Scholar
  6. 6.
    Knight RL, Booth C, Wilcox HE, Fisher J, Ingham E. Tissue engineering of cardiac valves: re-seeding of acellular porcine aortic valve matrices with human mesenchymal progenitor cells. J Heart Valve Dis. 2005;14(6):806–13.PubMedGoogle Scholar
  7. 7.
    Schenke-Layland K. Complete dynamic repopulation of decellularized heart valves by application of defined physical signals—an in vitro study. Cardiovasc Res. 2003;60(3):497–509. Scholar
  8. 8.
    Weber B, Dijkman PE, Scherman J, Sanders B, Emmert MY, Grünenfelder J, et al. Off-the-shelf human decellularized tissue-engineered heart valves in a non-human primate model. Biomaterials. 2013;34(30):7269–80. Scholar
  9. 9.
    Shinoka T, Breuer CK, Tanel RE, Zund G, Miura T, Ma PX, et al. Tissue engineering heart valves: valve leaflet replacement study in a lamb model. Ann Thorac Surg. 1995;60(95):S513–6. Scholar
  10. 10.
    Hoerstrup SP, Sodian R, Daebritz S, Wang J, Bacha EA, Martin DP, et al. Functional living trileaflet heart valves grown in vitro. Circulation. 2000;102(19 Suppl 3):III44–9. Scholar
  11. 11.
    Mol A, Driessen NJB, Rutten MCM, Hoerstrup SP, Bouten CVC, Baaijens FPT. Tissue engineering of human heart valve leaflets: a novel bioreactor for a strain-based conditioning approach. Ann Biomed Eng. 2005;33(12):1778–88. Scholar
  12. 12.
    Schmidt D, Mol A, Breymann C, Achermann J, Odermatt B, Go M, et al. Living autologous heart valves engineered from human prenatally harvested progenitors. Circulation. 2006;114:125–32. Scholar
  13. 13.
    Sutherland FWH, Perry TE, Yu Y, Sherwood MC, Rabkin E, Masuda Y, et al. From stem cells to viable autologous semilunar heart valve. Circulation. 2005;111:2783–91. Scholar
  14. 14.
    Dohmen PM, da Costa F, Holinski S, Lopes SV, Yoshi S, Reichert LH, et al. Is there a possibility for a glutaraldehyde-free porcine heart valve to grow? Eur Surg Res. 2006;38(1):54–61. Scholar
  15. 15.
    Goldstein S, Clarke DR, Walsh SP, Black KS, O’Brien MF. Transpecies heart valve transplant: advanced studies of a bioengineered xeno-autograft. Ann Thorac Surg. 2000;70(6):1962–9. Scholar
  16. 16.
    Leyh RG, Wilhelmi M, Rebe P, Fischer S, Kofidis T, Haverich A, et al. In vivo repopulation of xenogeneic and allogeneic acellular valve matrix conduits in the pulmonary circulation. Ann Thorac Surg. 2003;75(5):1457–63; discussion 1463.CrossRefGoogle Scholar
  17. 17.
    Dijkman PE, Driessen-Mol A, Frese L, Hoerstrup SP, Baaijens FPT. Decellularized homologous tissue-engineered heart valves as off-the-shelf alternatives to xeno- and homografts. Biomaterials. 2012;33(18):4545–54. Scholar
  18. 18.
    Driessen-Mol A, Emmert MY, Dijkman PE, Frese L, Sanders B, Weber B, et al. 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(13):1320–9. Scholar
  19. 19.
    Flanagan TC, Cornelissen C, Koch S, Tschoeke B, Sachweh JS, Schmitz-Rode T, et al. The in vitro development of autologous fibrin-based tissue-engineered heart valves through optimised dynamic conditioning. Biomaterials. 2007;28(23):3388–97. Scholar
  20. 20.
    Mol A, Smits AIPM, Bouten CVC, Baaijens FPT. Tissue engineering of heart valves: advances and current challenges. Expert Rev Med Devices. 2009;6(3):259–75. Scholar
  21. 21.
    Sacks MS, Schoen FJ, Mayer JE. Bioengineering challenges for heart valve tissue engineering. Annu Rev Biomed Eng. 2009;11(1):289–313. Scholar
  22. 22.
    Anderson RH. The surgical anatomy of the aortic root. Multimed Man Cardiothorac Surg. 2007;102:1–8. Scholar
  23. 23.
    Thubrikar MJ. The aortic valve. Boca Raton, FL: CRC Press; 1990. 232 pGoogle Scholar
  24. 24.
    Sutton JP, Ho SY, Anderson RH. The forgotten interleaflet triangles: a review of the surgical anatomy of the aortic valve. Ann Thorac Surg. 1995;59(2):419–27.CrossRefGoogle Scholar
  25. 25.
    Balachandran K, Sucosky P, Yoganathan AP. Hemodynamics and mechanobiology of aortic valve inflammation and calcification. Int J Inflam. 2011;2011:263870. Scholar
  26. 26.
    Billiar KL, Sacks MS. Biaxial mechanical properties of the natural and glutaraldehyde treated aortic valve cusp—part I: experimental results. J Biomech Eng. 2000;122(1):23–30. Scholar
  27. 27.
    Mavrilas D, Missirlis Y. An approach to the optimization of preparation of bioprosthetic heart valves. J Biomech. 1991;24(5):331–9.CrossRefGoogle Scholar
  28. 28.
    Sacks MS, Yoganathan AP. Heart valve function: a biomechanical perspective. Philos Trans R Soc Lond B Biol Sci. 2007;362(1484):1369–91. Scholar
  29. 29.
    Schoen FJ. Evolving concepts of cardiac valve dynamics: the continuum of development, functional structure, pathobiology, and tissue engineering. Circulation. 2008;118(18):1864–80. Scholar
  30. 30.
    Ho SY. Structure and anatomy of the aortic root. Eur J Echocardiogr. 2009;10(1):i3–10. Scholar
  31. 31.
    Scott MJ, Vesely I. Morphology of porcine aortic valve cusp elastin. J Heart Valve Dis. 1996;5(5):464–71.PubMedGoogle Scholar
  32. 32.
    Buchanan RM, Sacks MS. Interlayer micromechanics of the aortic heart valve leaflet. Biomech Model Mechanobiol. 2014;13(4):813–26. Scholar
  33. 33.
    Hasan A, Ragaert K, Swieszkowski W, Selimovi Š, Paul A, Camci-Unal G, et al. Biomechanical properties of native and tissue engineered heart valve constructs. J Biomech. 2014;47:1949–63. Scholar
  34. 34.
    Boerboom RA, Rubbens MP, Driessen NJB, Bouten CVC, Baaijens FPT. Effect of strain magnitude on the tissue properties of engineered cardiovascular constructs. Ann Biomed Eng. 2008;36(2):244–53. Scholar
  35. 35.
    Cox MAJ, Kortsmit J, Driessen NJB, Bouten CVC, Baaijens FPT. Tissue-engineered heart valves develop native-like collagen fiber architecture. Tissue Eng Part A. 2010;16(5):1527–37.CrossRefGoogle Scholar
  36. 36.
    Engelmayr GC, Papworth GD, Watkins SC, Mayer JE, Sacks MS. Guidance of engineered tissue collagen orientation by large-scale scaffold microstructures. J Biomech. 2006;39(10):1819–31. Scholar
  37. 37.
    Engelmayr GC, Rabkin E, Sutherland FWH, Schoen FJ, Mayer JE, Sacks MS. The independent role of cyclic flexure in the early in vitro development of an engineered heart valve tissue. Biomaterials. 2005;26(2):175–87. Scholar
  38. 38.
    Engelmayr GC, Sales VL, Mayer JE, Sacks MS. Cyclic flexure and laminar flow synergistically accelerate mesenchymal stem cell-mediated engineered tissue formation: implications for engineered heart valve tissues. Biomaterials. 2006;27(36):6083–95. Scholar
  39. 39.
    Neidert MR, Tranquillo RT. Tissue-engineered valves with commissural alignment. Tissue Eng. 2006;12(4):891–903. Scholar
  40. 40.
    Ramaswamy S, Boronyak SM, Le T, Holmes A, Sotiropoulos F, Sacks MS. A novel bioreactor for mechanobiological studies of engineered heart valve tissue formation under pulmonary arterial physiological flow conditions. J Biomech Eng. 2014;136:1–14. Scholar
  41. 41.
    Ramaswamy S, Gottlieb D, Engelmayr GC, Aikawa E, Schmidt DE, Gaitan-Leon DM, et al. The role of organ level conditioning on the promotion of engineered heart valve tissue development in-vitro using mesenchymal stem cells. Biomaterials. 2010;31(6):1114–25. Scholar
  42. 42.
    Balguid A, Rubbens MP, Mol A, Bank RA, Bogers AJJC, van Kats JP, et al. The role of collagen cross-links in biomechanical behavior of human aortic heart valve leaflets—relevance for tissue engineering. Tissue Eng. 2007;13(7):1501–11. Scholar
  43. 43.
    Driessen NJB, Mol A, Bouten CVC, Baaijens FPT. Modeling the mechanics of tissue-engineered human heart valve leaflets. J Biomech. 2007;40(2):325–34. Scholar
  44. 44.
    Mol A, Rutten MCM, Driessen NJB, Bouten CVC, Zünd G, Baaijens FPT, et al. Autologous human tissue-engineered heart valves: prospects for systemic application. Circulation. 2006;114(Suppl. 1):152–9. Scholar
  45. 45.
    Schmidt D, Dijkman PE, Driessen-Mol A, Stenger R, Mariani C, Puolakka A, et al. Minimally-invasive implantation of living tissue engineered heart valves: a comprehensive approach from autologous vascular cells to stem cells. J Am Coll Cardiol. 2010;56(6):510–20. Scholar
  46. 46.
    Sodian R, Hoerstrup SP, Sperling JS, Daebritz S, Martin DP, Moran AM, et al. Early in vivo experience with tissue-engineered trileaflet heart valves. Circulation. 2000;102:III22–9.CrossRefGoogle Scholar
  47. 47.
    Syedain ZH, Lahti MT, Johnson SL, Robinson PS, Ruth GR, Bianco RW, et al. Implantation of a tissue-engineered heart valve from human fibroblasts exhibiting short term function in the sheep pulmonary artery. Cardiovasc Eng Technol. 2011;2(2):101–12. Scholar
  48. 48.
    Flanagan TC, Sachweh JS, Frese J, Schnöring H, Gronloh N, Koch S, et al. In vivo remodeling and structural characterization of fibrin-based tissue-engineered heart valves in the adult sheep model. Tissue Eng Part A. 2009;15(10):2965–76. Scholar
  49. 49.
    Gottlieb D, Kunal T, Emani S, Aikawa E, Brown DW, Powell AJ, et al. In vivo monitoring of function of autologous engineered pulmonary valve. J Thorac Cardiovasc Surg. 2010;139(3):723–31. Scholar
  50. 50.
    Loerakker S, Argento G, Oomens CWJ, Baaijens FPT. Effects of valve geometry and tissue anisotropy on the radial stretch and coaptation area of tissue-engineered heart valves. J Biomech. 2013;46(11):1792–800. Scholar
  51. 51.
    Sanders B, Loerakker S, Fioretta ES, Bax DJP, Driessen-Mol A, Hoerstrup SP, et al. Improved geometry of decellularized tissue engineered heart valves to prevent leaflet retraction. Ann Biomed Eng. 2016;44:1061–71. Scholar
  52. 52.
    Rock CA, Han L, Doehring TC. Complex collagen fiber and membrane morphologies of the whole porcine aortic valve. PLoS One. 2014;9(1):e86087. Scholar
  53. 53.
    Oomen PJA, Loerakker S, van Geemen D, Neggers J, Goumans MTH, van den Bogaerdt AJ, et al. Age-dependent changes of stress and strain in the human heart valve and their relation with collagen remodeling. Acta Biomater. 2016;29:161–9. Scholar
  54. 54.
    Sacks MS, Smith DB. A small angle light scattering device for planar connective tissue microstructural analysis. Ann Biomed Eng. 1997;25(4):678–89.CrossRefGoogle Scholar
  55. 55.
    Sacks MS, Smith DB, Hiester ED. The aortic valve microstructure: effects of transvalvular pressure. J Biomed Mater Res. 1998;41(1):131–41.<131::AID-JBM16>3.0.CO;2-Q.CrossRefGoogle Scholar
  56. 56.
    Aikawa E. Human semilunar cardiac valve remodeling by activated cells from fetus to adult: implications for postnatal adaptation, pathology, and tissue engineering. Circulation. 2006;113(10):1344–52. Scholar
  57. 57.
    Rubbens MP, Driessen-Mol A, Boerboom RA, Koppert MMJ, van Assen HC, TerHaar Romeny BM, et al. Quantification of the temporal evolution of collagen orientation in mechanically conditioned engineered cardiovascular tissues. Ann Biomed Eng. 2009;37(7):1263–72. Scholar
  58. 58.
    Thomopoulos S, Fomovsky GM, Holmes JW. The development of structural and mechanical anisotropy in fibroblast populated collagen gels. J Biomech Eng. 2005;127(5):742–50. Scholar
  59. 59.
    Costa KD, Lee EJ, Holmes JW. Creating alignment and anisotropy in engineered heart tissue: role of boundary conditions in a model three-dimensional culture system. Tissue Eng. 2003;9(4):567–77. Scholar
  60. 60.
    Kostyuk O, Brown RA. Novel spectroscopic technique for in situ monitoring of collagen fibril alignment in gels. Biophys J. 2004;87(1):648–55. Scholar
  61. 61.
    Boerboom RA, Driessen NJB, Bouten CVC, Huyghe JM, Baaijens FPT. Finite element model of mechanically induced collagen fiber synthesis and degradation in the aortic valve. Ann Biomed Eng. 2003;31(9):1040–53. Scholar
  62. 62.
    Creane A, Maher E, Sultan S, Hynes N, Kelly DJ, Lally C. Prediction of fibre architecture and adaptation in diseased carotid bifurcations. Biomech Model Mechanobiol. 2011;10(6):831–43. Scholar
  63. 63.
    Driessen NJB, Boerboom RA, Huyghe JM, Bouten CVC, Baaijens FPT. Computational analyses of mechanically induced collagen fiber remodeling in the aortic heart valve. J Biomech Eng. 2003;125(4):549–57. Scholar
  64. 64.
    Driessen NJB, Bouten CVC, Baaijens FPT. Improved prediction of the collagen fiber architecture in the aortic heart valve. J Biomech Eng. 2005;127(2):329. Scholar
  65. 65.
    Driessen NJB, Cox MAJ, Bouten CVC, Baaijens FPT. Remodelling of the angular collagen fiber distribution in cardiovascular tissues. Biomech Model Mechanobiol. 2008;7(2):93–103. Scholar
  66. 66.
    Driessen NJB, Peters GWM, Huyghe JM, Bouten CVC, Baaijens FPT. Remodelling of continuously distributed collagen fibres in soft connective tissues. J Biomech. 2003;36(8):1151–8. Scholar
  67. 67.
    Driessen NJB, Wilson W, Bouten CVC, Baaijens FPT. A computational model for collagen fibre remodelling in the arterial wall. J Theor Biol. 2004;226(1):53–64. Scholar
  68. 68.
    Hariton I, DeBotton G, Gasser TC, Holzapfel G a. Stress-driven collagen fiber remodeling in arterial walls. Biomech Model Mechanobiol. 2007;6(3):163–75. Scholar
  69. 69.
    Kuhl E, Holzapfel GA. A continuum model for remodeling in living structures. J Mater Sci. 2007;42(21):8811–23. Scholar
  70. 70.
    Menzel A, Harrysson M, Ristinmaa M. Towards an orientation-distribution-based multi-scale approach for remodelling biological tissues. Comput Methods Biomech Biomed Eng. 2008;11(5):505–24. Scholar
  71. 71.
    Menzel A, Waffenschmidt T. A microsphere-based remodelling formulation for anisotropic biological tissues. Philos Trans A Math Phys Eng Sci. 2009;367(1902):3499–523. Scholar
  72. 72.
    Sáez P, Peña E, Doblaré M, Martinez MÁ. An anisotropic microsphere-based approach for fiber orientation adaptation in soft tissue. IEEE Trans Biomed Eng. 2011;58(12 Part 2):3500–3. Scholar
  73. 73.
    Kuhl E, Garikipati K, Arruda EM, Grosh K. Remodeling of biological tissue: mechanically induced reorientation of a transversely isotropic chain network. J Mech Phys Solids. 2005;53(7):1552–73. Scholar
  74. 74.
    Menzel A. Modelling of anisotropic growth in biological tissues: a new approach and computational aspects. Biomech Model Mechanobiol. 2005;3(3):147–71. Scholar
  75. 75.
    Schriefl AJ, Reinisch AJ, Sankaran S, Pierce DM, Holzapfel GA. Quantitative assessment of collagen fibre orientations from two-dimensional images of soft biological tissues. J R Soc Interface. 2012;9:3081–93. Scholar
  76. 76.
    Holzapfel GA, Gasser TC, Ogden RW. A new constitutive framework for arterial wall mechanics and a comperative study of material models. J Elast. 2000;61:1–48.CrossRefGoogle Scholar
  77. 77.
    Sauren AAHJ. The mechanical behaviour of the aortic valve. PhD Thesis Eindhoven: Technische Hogeschool Eindhoven. 1981.
  78. 78.
    Sander EA, Barocas VH, Tranquillo RT. Initial fiber alignment pattern alters extracellular matrix synthesis in fibroblast-populated fibrin gel cruciforms and correlates with predicted tension. Ann Biomed Eng. 2011;39(2):714–29. Scholar
  79. 79.
    Meshel AS, Wei Q, Adelstein RS, Sheetz MP. Basic mechanism of three-dimensional collagen fibre transport by fibroblasts. Nat Cell Biol. 2005;7(2):157–64. Scholar
  80. 80.
    Wang JH-C, Jia F, Gilbert TW, Woo SL-Y. Cell orientation determines the alignment of cell-produced collagenous matrix. J Biomech. 2003;36(1):97–102. Scholar
  81. 81.
    Burridge K, Wittchen ES. The tension mounts: stress fibers as force-generating mechanotransducers. J Cell Biol. 2013;200(1):9–19. Scholar
  82. 82.
    Engler AJ, Sen S, Sweeney HL, Discher DE. Matrix elasticity directs stem cell lineage specification. Cell. 2006;126(4):677–89. Scholar
  83. 83.
    Foolen J, Deshpande VS, Kanters FMW, Baaijens FPT. The influence of matrix integrity on stress-fiber remodeling in 3D. Biomaterials. 2012;33(30):7508–18. Scholar
  84. 84.
    Ghibaudo M, Saez A, Trichet L, Xayaphoummine A, Browaeys J, Silberzan P, et al. Traction forces and rigidity sensing regulate cell functions. Soft Matter. 2008;4(9):1836. Scholar
  85. 85.
    Van Vlimmeren MAA, Driessen-Mol A, Oomens CWJ, Baaijens FPT. Passive and active contributions to generated force and retraction in heart valve tissue engineering. Biomech Model Mechanobiol. 2012;11(7):1015–27. Scholar
  86. 86.
    Kaunas R, Usami S, Chien S. Regulation of stretch-induced JNK activation by stress fiber orientation. Cell Signal. 2006;18(11):1924–31. Scholar
  87. 87.
    Tondon A, Hsu HJ, Kaunas R. Dependence of cyclic stretch-induced stress fiber reorientation on stretch waveform. J Biomech. 2012;45(5):728–35. Scholar
  88. 88.
    Wang JH. Substrate deformation determines actin cytoskeleton reorganization: a mathematical modeling and experimental study. J Theor Biol. 2000;202(1):33–41. Scholar
  89. 89.
    Faust U, Hampe N, Rubner W, Kirchgeßner N, Safran S, Hoffmann B, et al. Cyclic stress at mHz frequencies aligns fibroblasts in direction of zero strain. PLoS One. 2011;6(12):e28963. Scholar
  90. 90.
    Obbink-Huizer C, Oomens CWJ, Loerakker S, Foolen J, Bouten CVC, Baaijens FPT. Computational model predicts cell orientation in response to a range of mechanical stimuli. Biomech Model Mechanobiol. 2014;13(1):227–36. Scholar
  91. 91.
    Tondon A, Kaunas R. The direction of stretch-induced cell and stress fiber orientation depends on collagen matrix stress. PLoS One. 2014;9(2):e89592. Scholar
  92. 92.
    Lamers E, Frank Walboomers X, Domanski M, te Riet J, van Delft FCMJM, Luttge R, et al. The influence of nanoscale grooved substrates on osteoblast behavior and extracellular matrix deposition. Biomaterials. 2010;31(12):3307–16. Scholar
  93. 93.
    Foolen J, Janssen-van den Broek MWJT, Baaijens FPT. Synergy between Rho signaling and matrix density in cyclic stretch-induced stress fiber organization. Acta Biomater. 2014;10(5):1876–85. Scholar
  94. 94.
    De Jonge N, Kanters FMW, Baaijens FPT, Bouten CVC. Strain-induced collagen organization at the micro-level in fibrin-based engineered tissue constructs. Ann Biomed Eng. 2013;41(4):763–74. Scholar
  95. 95.
    Prodanov L, te Riet J, Lamers E, Domanski M, Luttge R, van Loon JJWA, et al. The interaction between nanoscale surface features and mechanical loading and its effect on osteoblast-like cells behavior. Biomaterials. 2010;31(30):7758–65. Scholar
  96. 96.
    Niklason LE, Yeh AT, Calle EA, Bai Y, Valentín A, Humphrey JD. Enabling tools for engineering collagenous tissues integrating bioreactors, intravital imaging, and biomechanical modeling. Proc Natl Acad Sci U S A. 2010;107(8):3335–9. Scholar
  97. 97.
    Hill AV. The heat of shortening and the dynamic constants of muscle. Proc R Soc Lond B Biol Sci. 1938;126:136–95.CrossRefGoogle Scholar
  98. 98.
    Deshpande VS, McMeeking RM, Evans AG. A bio-chemo-mechanical model for cell contractility. Proc Natl Acad Sci USA. 2006;103(38):14015–20.CrossRefGoogle Scholar
  99. 99.
    Kaunas R, Hsu H-J. A kinematic model of stretch-induced stress fiber turnover and reorientation. J Theor Biol. 2009;257(2):320–30. Scholar
  100. 100.
    Hsu H-J, Lee C-F, Kaunas R. A dynamic stochastic model of frequency-dependent stress fiber alignment induced by cyclic stretch. PLoS One. 2009;4(3):e4853. Scholar
  101. 101.
    Kaunas R, Hsu HJ, Deguchi S. Sarcomeric model of stretch-induced stress fiber reorganization. Cell Health Cytoskelet. 2011;3(1):13–22. Scholar
  102. 102.
    Vernerey FJ, Farsad M. A constrained mixture approach to mechano-sensing and force generation in contractile cells. J Mech Behav Biomed Mater. 2011;4(8):1683–99. Scholar
  103. 103.
    Foucard L, Vernerey FJ. A thermodynamical model for stress-fiber organization in contractile cells. Appl Phys Lett. 2012;100(1):13702–137024. Scholar
  104. 104.
    Vigliotti A, Ronan W, Baaijens FPT, Deshpande VS. A thermodynamically motivated model for stress-fiber reorganization. Biomech Model Mechanobiol. 2016;15:761–89. Scholar
  105. 105.
    Deshpande VS, McMeeking RM, Evans AG. A model for the contractility of the cytoskeleton including the effects of stress-fibre formation and dissociation. Proc R Soc A Math Phys Eng Sci. 2007;463(2079):787–815. Scholar
  106. 106.
    Wei Z, Deshpande VS, McMeeking RM, Evans AG. Analysis and interpretation of stress fiber organization in cells subject to cyclic stretch. J Biomech Eng. 2008;130(3):031009–1. Scholar
  107. 107.
    Deshpande VS, Mrksich M, McMeeking RM, Evans AG. A bio-mechanical model for coupling cell contractility with focal adhesion formation. J Mech Phys Solids. 2008;56(4):1484–510. Scholar
  108. 108.
    Pathak A, McMeeking RM, Evans AG, Deshpande VS. An analysis of the cooperative mechano-sensitive feedback between intracellular signaling, focal adhesion development, and stress fiber contractility. J Appl Mech. 2011;78(4):041001. Scholar
  109. 109.
    Pathak A, Deshpande VS, McMeeking RM, Evans AG. The simulation of stress fibre and focal adhesion development in cells on patterned substrates. J R Soc Interface. 2008;5(22):507–24. Scholar
  110. 110.
    Ronan W, Deshpande VS, McMeeking RM, McGarry JP. Cellular contractility and substrate elasticity: a numerical investigation of the actin cytoskeleton and cell adhesion. Biomech Model Mechanobiol. 2014;13(2):417–35. Scholar
  111. 111.
    Vigliotti A, Mcmeeking RM, Deshpande VS. Simulation of the cytoskeletal response of cells on grooved or patterned substrates. Interface. 2015;12:20141320. Scholar
  112. 112.
    Ristori T, Vigliotti A, Baaijens FPT, Loerakker S, Deshpande VS. Prediction of cell alignment on cyclically strained grooved substrates. Biophys J. 2016;111(10):2274–85. Scholar
  113. 113.
    Breen EC. Mechanical strain increases type I collagen expression in pulmonary fibroblasts in vitro. J Appl Physiol. 2000;88:203–9.CrossRefGoogle Scholar
  114. 114.
    Butt R, Bishop JE. Mechanical load enhances the stimulatory effect of PDGF on pulmonary artery fibroblast procollagen synthesis. Chest. 1998;114(1):25S. Scholar
  115. 115.
    Yang G, Crawford RC, Wang JH-C. Proliferation and collagen production of human patellar tendon fibroblasts in response to cyclic uniaxial stretching in serum-free conditions. J Biomech. 2004;37(10):1543–50. Scholar
  116. 116.
    Visse R. Matrix metalloproteinases and tissue inhibitors of metalloproteinases: structure, function, and biochemistry. Circ Res. 2003;92(8):827–39. Scholar
  117. 117.
    Wojtowicz-Praga SM, Dickson RB, Hawkins MJ. Matrix metalloproteinase inhibitors. Invest New Drugs. 1997;15(1):61–75.CrossRefGoogle Scholar
  118. 118.
    Shelton L, Rada JS. Effects of cyclic mechanical stretch on extracellular matrix synthesis by human scleral fibroblasts. Exp Eye Res. 2007;84(2):314–22. Scholar
  119. 119.
    Yang G, Im H-J, Wang JH-C. Repetitive mechanical stretching modulates IL-1β induced COX-2, MMP-1 expression, and PGE2 production in human patellar tendon fibroblasts. Gene. 2005;363:166–72. Scholar
  120. 120.
    Bhole AP, Flynn BP, Liles M, Saeidi N, Dimarzio CA, Ruberti JW. Mechanical strain enhances survivability of collagen micronetworks in the presence of collagenase: implications for load-bearing matrix growth and stability. Philos Trans R Soc A Math Phys Eng Sci. 2009;367(1902):3339–62. Scholar
  121. 121.
    Huang C, Yannas IV. Mechanochemical studies of enzymatic degradation of insoluble collagen fibers. J Biomed Mater Res. 1977;11(1):137–54. Scholar
  122. 122.
    Ruberti JW, Hallab NJ. Strain-controlled enzymatic cleavage of collagen in loaded matrix. Biochem Biophys Res Commun. 2005;336(2):483–9. Scholar
  123. 123.
    Wyatt KE-K, Bourne JW, Torzilli PA. Deformation-dependent enzyme mechanokinetic cleavage of type I collagen. J Biomech Eng. 2009;131(5):051004. Scholar
  124. 124.
    van Vlimmeren MAA, Driessen-Mol A, Oomens CWJ, Baaijens FPT. Model system to quantify stress generation, compaction, and retraction in engineered heart valve tissue. Tissue Eng Part C Methods. 2011;17(10):983–91. Scholar
  125. 125.
    Rausch MK, Kuhl E. On the effect of prestrain and residual stress in thin biological membranes. J Mech Phys Solids. 2013;61(9):1955–69. Scholar
  126. 126.
    Grenier G, Rémy-Zolghadri M, Larouche D, Gauvin R, Baker K, Bergeron F, et al. Tissue reorganization in response to mechanical load increases functionality. Tissue Eng. 2005;11(1–2):90–100. Scholar
  127. 127.
    Soares ALF, Stekelenburg M, Baaijens FPT. Remodeling of the collagen fiber architecture due to compaction in small vessels under tissue engineered conditions. J Biomech Eng. 2011;133(7):071002. Scholar
  128. 128.
    Nagel T, Kelly DJ. Remodelling of collagen fibre transition stretch and angular distribution in soft biological tissues and cell-seeded hydrogels. Biomech Model Mechanobiol. 2012;11(3–4):325–39. Scholar
  129. 129.
    Foolen J, van Donkelaar CC, Soekhradj-Soechit S, Ito K. European Society of Biomechanics S.M. Perren Award 2010: an adaptation mechanism for fibrous tissue to sustained shortening. J Biomech. 2010;43(16):3168–76. Scholar
  130. 130.
    Valentín A, Cardamone L, Baek S, Humphrey JD. Complementary vasoactivity and matrix remodelling in arterial adaptations to altered flow and pressure. J R Soc Interface. 2009;6(32):293–306. Scholar
  131. 131.
    Valentín A, Humphrey JD, Holzapfel GA. A finite element-based constrained mixture implementation for arterial growth, remodeling, and adaptation: theory and numerical verification. Int J Numer Method Biomed Eng. 2013;29(8):822–49. Scholar
  132. 132.
    Baek S, Rajagopal KR, Humphrey JD. A theoretical model of enlarging intracranial fusiform aneurysms. J Biomech Eng. 2006;128(1):142. Scholar
  133. 133.
    Baek S, Valentín A, Humphrey JD. Biochemomechanics of cerebral vasospasm and its resolution: II. Constitutive relations and model simulations. Ann Biomed Eng. 2007;35(9):1498–509. Scholar
  134. 134.
    Miller KS, Khosravi R, Breuer CK, Humphrey JD. A hypothesis-driven parametric study of effects of polymeric scaffold properties on tissue engineered neovessel formation. Acta Biomater. 2015;11:283–94. Scholar
  135. 135.
    Khosravi R, Miller KS, Best CA, Shih YC, Lee Y-U, Yi T, et al. Biomechanical diversity despite mechanobiological stability in tissue engineered vascular grafts two years post-implantation. Tissue Eng Part A. 2015;21:1529–38. Scholar
  136. 136.
    Heck TAM, Wilson W, Foolen J, Cilingir AC, Ito K, van Donkelaar CC. A tissue adaptation model based on strain-dependent collagen degradation and contact-guided cell traction. J Biomech. 2015;48(5):823–31. Scholar
  137. 137.
    van Donkelaar CC, Heck TAM, Wilson W, Foolen J, Ito K. Versatility of a collagen adaptation model that includes strain-dependent degeneration and cell traction. Vol. 1A: Abdominal aortic aneurysms; active and reactive soft matter; atherosclerosis; biofluid mechanics; education; biotransport phenomena; bone, joint and spine mechanics; brain injury; cardiac mechanics; cardiovascular devices, fluids and imaging, C. ASME; 2013. p. V01AT02A003.
  138. 138.
    Ellsmere JC, Khanna RA, Lee JM. Mechanical loading of bovine pericardium accelerates enzymatic degradation. Biomaterials. 1999;20(v):1143–50. Scholar
  139. 139.
    Lee EJ, Holmes JW, Costa KD. Remodeling of engineered tissue anisotropy in response to altered loading conditions. Ann Biomed Eng. 2008;36(8):1322–34. Scholar
  140. 140.
    Hu J-J, Humphrey JD, Yeh AT. Characterization of engineered tissue development under biaxial stretch using nonlinear optical microscopy. Tissue Eng Part A. 2009;15(7):1553–64. Scholar
  141. 141.
    Soares ALF, Oomens CWJ, Baaijens FPT. A computational model to describe the collagen orientation in statically cultured engineered tissues. Comput Methods Biomech Biomed Engin. 2014;17:251–62. Scholar
  142. 142.
    Loerakker S, Obbink-Huizer C, Baaijens FPT. A physically motivated constitutive model for cell-mediated compaction and collagen remodeling in soft tissues. Biomech Model Mechanobiol. 2014;13(5):985–1001. Scholar
  143. 143.
    Loerakker S, Ristori T, Baaijens FPT. A computational analysis of cell-mediated compaction and collagen remodeling in tissue-engineered heart valves. J Mech Behav Biomed Mater. 2016;58:173–87. Scholar
  144. 144.
    Ristori T, Obbink-Huizer C, Oomens CWJ, Baaijens FPT, Loerakker S. Efficient computational simulation of actin stress fiber remodeling. Comput Methods Biomech Biomed Engin. 2016;19(12):1347–58. Scholar
  145. 145.
    Humphrey JD, Rajagopal KR. A constrained mixture model for growth and remodeling of soft tissues. Math Model Methods Appl Sci. 2002;12(03):407–30. Scholar
  146. 146.
    Kuhl E. Growing matter: a review of growth in living systems. J Mech Behav Biomed Mater. 2014;29:529–43. Scholar
  147. 147.
    Kuhl E, Maas R, Himpel G, Menzel A. Computational modeling of arterial wall growth. Biomech Model Mechanobiol. 2007;6(5):321–31. Scholar
  148. 148.
    Zöllner AM, Abilez OJ, Böl M, Kuhl E. Stretching skeletal muscle: chronic muscle lengthening through sarcomerogenesis. PLoS One. 2012;7(10):e45661. Scholar
  149. 149.
    Zöllner AM, Buganza Tepole A, Gosain AK, Kuhl E. Growing skin: tissue expansion in pediatric forehead reconstruction. Biomech Model Mechanobiol. 2012;11(6):855–67. Scholar
  150. 150.
    Göktepe S, Acharya SNS, Wong J, Kuhl E. Computational modeling of passive myocardium. Int J Numer Method Biomed Eng. 2011;27(1):1–12. Scholar
  151. 151.
    Werfel J, Krause S, Bischof AG, Mannix RJ, Tobin H, Bar-Yam Y, et al. How changes in extracellular matrix mechanics and gene expression variability might combine to drive cancer progression. PLoS One. 2013;8(10):e76122. Scholar
  152. 152.
    Rouillard AD, Holmes JW. Coupled agent-based and finite-element models for predicting scar structure following myocardial infarction. Prog Biophys Mol Biol. 2014;115(2–3):235–43. Scholar
  153. 153.
    Rouillard AD, Holmes JW. Mechanical regulation of fibroblast migration and collagen remodelling in healing myocardial infarcts. J Physiol. 2012;590(Pt 18):4585–602. Scholar
  154. 154.
    Fomovsky GM, Holmes JW. Evolution of scar structure, mechanics, and ventricular function after myocardial infarction in the rat. Am J Physiol Heart Circ Physiol. 2010;298(1):H221–8. Scholar

Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  • T. Ristori
    • 1
    • 2
  • A. J. van Kelle
    • 1
    • 2
  • F. P. T. Baaijens
    • 1
    • 2
  • S. Loerakker
    • 1
    • 2
    Email author
  1. 1.Department of Biomedical EngineeringEindhoven University of TechnologyEindhovenThe Netherlands
  2. 2.Institute for Complex Molecular Systems, Eindhoven University of TechnologyEindhovenThe Netherlands

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