Prediction of matrix-to-cell stress transfer in heart valve tissues

Abstract

Non-linear and anisotropic heart valve leaflet tissue mechanics manifest principally from the stratification, orientation, and inhomogeneity of their collagenous microstructures. Disturbance of the native collagen fiber network has clear consequences for valve and leaflet tissue mechanics and presumably, by virtue of their intimate embedment, on the valvular interstitial cell stress–strain state and concomitant phenotype. In the current study, a set of virtual biaxial stretch experiments were conducted on porcine pulmonary valve leaflet tissue photomicrographs via an image-based finite element approach. Stress distribution evolution during diastolic valve closure was predicted at both the tissue and cellular levels. Orthotropic material properties consistent with distinct stages of diastolic loading were applied. Virtual experiments predicted tissue- and cellular-level stress fields, providing insight into how matrix-to-cell stress transfer may be influenced by the inhomogeneous collagen fiber architecture, tissue anisotropic material properties, and the cellular distribution within the leaflet tissue. To the best of the authors’ knowledge, this is the first study reporting on the evolution of stress fields at both the tissue and cellular levels in valvular tissue and thus contributes toward refining our collective understanding of valvular tissue micromechanics while providing a computational tool enabling the further study of valvular cell–matrix interactions.

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References

  1. 1.

    American Heart Association.: Heart Disease and Stroke Statistics. (2010)

  2. 2.

    NIH. Heart and Vascular Diseases. National Heart Lung and Blood Institute, (2010)

  3. 3.

    El Khoury, G., Vanoverschelde, J.L., Glineur, D., Pierard, F., Verhelst, R.R., Rubay, J., Funken, J.C., Watremez, C., Astarci, P., Lacroix, V., Poncelet, A., Noirhomme, P.: Repair of bicuspid aortic valves in patients with aortic regurgitation. Circulation 114, I610–I616 (2006)

    Article  Google Scholar 

  4. 4.

    El Oakley, R., Kleine, P., Bach, D.S.: Choice of prosthetic heart valve in today's practice. Circulation 117(2), 253–256 (2008)

    Article  Google Scholar 

  5. 5.

    Mendelson, K., Schoen, F.J.: Heart valve tissue engineering: Concepts, approaches, progress, and challenges. Ann. Biomed. Eng. 34(12), 1799–1819 (2006)

    Article  Google Scholar 

  6. 6.

    Christie, G.W., Barratt-Boyes, B.G.: Mechanical properties of porcine pulmonary valve leaflets—how do they differ from aortic leaflets. Ann. Thorac. Surg. 60(2), S195–S199 (1995)

    Article  Google Scholar 

  7. 7.

    Billiar, K.L., Sacks, M.S.: Biaxial mechanical properties of the natural and glutaraldehyde treated aortic valve cusp - Part I: Experimental results. J. Biomech. Eng.-Trans. ASME 122(1), 23–30 (2000)

    Article  Google Scholar 

  8. 8.

    Stradins, P., Lacis, R., Ozolanta, I., Purina, B., Ose, V., Feldmane, L., Kasyanov, V.: Comparison of biomechanical and structural properties between human aortic and pulmonary valve. Eur. J. Cardio-thoracic Surg.: Eur. J. Cardio-Thoracic Surg. 26(3), 634–639 (2004)

    Article  Google Scholar 

  9. 9.

    Sacks, M.S., Schoen, F.J., Mayer, J.E.: Bioengineering challenges for heart valve tissue engineering. Annu. Rev. Biomed. Eng. 11, 289–313 (2009)

    Article  Google Scholar 

  10. 10.

    Sacks, M.S., Smith, D.B., Hiester, E.D.: The aortic valve microstructure: Effects of transvalvular pressure. J. Biomed. Mater. Res. 41(1), 131–141 (1998)

    Article  Google Scholar 

  11. 11.

    Joyce, E.M., Liao, J., Schoen, F.J., Mayer Jr., J.E., Sacks, M.S.: Functional collagen fiber architecture of the pulmonary heart valve cusp RID F-3703-2011. Ann. Thorac. Surg. 87(4), 1240–1249 (2009)

    Article  Google Scholar 

  12. 12.

    Cox, M.A.J., Kortsmit, J., Driessen, N., Bouten, C.V.C., Baaijens, F.P.T.: Tissue-engineered heart valves develop native-like collagen fiber architecture. Tissue Eng. Part a 16(5), 1527–1537 (2010)

    Article  Google Scholar 

  13. 13.

    Huang, H.-Y.S., Liao, J., Sacks, M.S.: In-situ deformation of the aortic valve interstitial cell nucleus under diastolic loading. J. Biomech. Eng. 129, 1–10 (2007)

    Google Scholar 

  14. 14.

    Huang, H.-Y.S., Balhouse, B.N., Huang, S.: Application of simple biomechanical and biochemical tests to heart valve leaflets: implications for heart valve characterization and tissue engineering. Proc. Inst. Mech. Eng. H J. Eng. Med. 226(11), 868–876 (2012)

    Article  Google Scholar 

  15. 15.

    Li, J., Luo, X.Y., Kuang, Z.B.: A nonlinear anisotropic model for porcine aortic heart valves. J. Biomech. 34(10), 1279–1289 (2001)

    Article  Google Scholar 

  16. 16.

    Luo, X.Y., Li, W.G., Li, J.: Geometrical stress-reducing factors in the anisotropic porcine heart valves. J. Biomech. Eng.-Trans. ASME 125(5), 735–744 (2003)

    Article  Google Scholar 

  17. 17.

    Mohammadi, H., Bahramian, F., Wan, W.: Advanced modeling strategy for the analysis of heart valve leaflet tissue mechanics using high-order finite element method. Med. Eng. Phys. 31(9), 1110–1117 (2009)

    Article  Google Scholar 

  18. 18.

    Koch, T.M., Reddy, B.D., Zilla, P., Franz, T.: Aortic valve leaflet mechanical properties facilitate diastolic valve function RID C-3386-2009. Comput. Methods Biomech. Biomed. Eng. 13(2), 225–234 (2010)

    Article  Google Scholar 

  19. 19.

    Balachandran, K., Konduri, S., Sucosky, P., Jo, H., Yoganathan, A.P.: An ex vivo study of the biological properties of porcine aortic valves in response to circumferential cyclic stretch. Ann. Biomed. Eng. 34(11), 1655–1665 (2006)

    Article  Google Scholar 

  20. 20.

    Merryman, W.D., Lukoff, H.D., Long, R.A., Engelmayr Jr., G.C., Hopkins, R.A., Sacks, M.S.: Synergistic effects of cyclic tension and transforming growth factor-β1 on the aortic valve myofibroblast. Cardiovasc. Pathol. 16(5), 268–276 (2007)

    Article  Google Scholar 

  21. 21.

    Metzler, S.A., Digesu, C.S., Howard, J.I., Filip To, S.D., Warnock, J.N.: Live en face imaging of aortic valve leaflets under mechanical stress. Biomech. Model. Mechanobiol. 11(3–4), 355–361 (2012)

    Article  Google Scholar 

  22. 22.

    Weston, M.W., Yoganathan, A.P.: Biosynthetic activity in heart valve leaflets in response to in vitro flow environments. Ann. Biomed. Eng. 29(9), 752–763 (2001)

    Article  Google Scholar 

  23. 23.

    Hutcheson, J.D., Venkataraman, R., Baudenbacher, F.J., Merryman, W.D.: Intracellular Ca(2+) accumulation is strain-dependent and correlates with apoptosis in aortic valve fibroblasts. J. Biomech. 45(5), 888–894 (2012)

    Article  Google Scholar 

  24. 24.

    Fisher, C.I., Chen, J., Merryman, W.D.: Calcific nodule morphogenesis by heart valve interstitial cells is strain dependent. Biomech. Model. Mechanobiol. 12(1), 5–17 (2013)

    Article  Google Scholar 

  25. 25.

    Quinlan, A.M., Billiar, K.L.: Investigating the role of substrate stiffness in the persistence of valvular interstitial cell activation. J. Biomed. Mater. Res. A 100(9), 2474–2482 (2012)

    Google Scholar 

  26. 26.

    Gould, R.A., Chin, K., Santisakultarm, T.P., Dropkin, A., Richards, J.M., Schaffer, C.B., Butcher, J.T.: Cyclic strain anisotropy regulates valvular interstitial cell phenotype and tissue remodeling in three-dimensional culture. Acta Biomater. 8(5), 1710–1719 (2012)

    Article  Google Scholar 

  27. 27.

    Waxman, A.S., Kornreich, B.G., Gould, R.A., Moise, N.S., Butcher, J.T.: Interactions between TGFβ1 and cyclic strain in modulation of myofibroblastic differentiation of canine mitral valve interstitial cells in 3D culture. J. Vet. Cardiol. 14(1), 211–221 (2012)

    Article  Google Scholar 

  28. 28.

    Eastwood, M., McGrouther, D.A., Brown, R.A.: Fibroblast responses to mechanical forces. Proc. Inst. Mech. Eng. Part H-J. Eng. Med. 212(H2), 85–92 (1998)

    Article  Google Scholar 

  29. 29.

    Liu, W.F. Mechanical regulation of cellular phenotype: implications for vascular tissue regeneration. Cardiovasc. Res. 95(2), 215–222 (2012)

  30. 30.

    Lewinsohn, A.D., Anssari-Benham, A., Lee, D.A., Taylor, P.M., Chester, A.H., Yacoub, M.H., Screen, H.R.C.: Anisotropic strain transfer through the aortic valve and its relevance to the cellular mechanical environment. Proc. Inst. Mech. Eng. Part H-J. Eng. Med. 225(H8), 821–830 (2011)

    Article  Google Scholar 

  31. 31.

    Huang, S., Huang, H.-Y.S.: Virtualisation of stress distribution in heart valve tissue. Comput. Methods Biomech. Biomed. Eng. 17(15), 1696–1704 (2014). doi:10.1080/10255842.2013.763937

    Article  Google Scholar 

  32. 32.

    Langer, S.A., Fuller, E., Carter, W.C.: OOF: An image-based finite-element analysis of material microstructures. Comput. Sci. Eng. 3(3), 15–23 (2001)

    Article  Google Scholar 

  33. 33.

    Reid, A.C.E., Lua, R.C., Garcia, R.E., Coffman, V.R., Langer, S.A.: Modelling microstructures with OOF2. Int. J. Mater. Prod. Tech. 35(3–4), 361–373 (2009)

    Article  Google Scholar 

  34. 34.

    Mirnajafi, A., Raymer, J.M., McClure, L.R., Sacks, M.S.: The flexural rigidity of the aortic valve leaflet in the commissural region. J. Biomech. 39(16), 2966–2973 (2006)

    Article  Google Scholar 

  35. 35.

    Sun, W., Huang, H.-Y.S., Argento, M.S. and Sacks, M.S. Finite element implementation of a structural constitutive model for planar collagenous tissues. 2003 Proceedings of the Second MIT Conference on Computational Solid and Fluid Mechanics, Cambridge, MA, (2003)

  36. 36.

    Sun, W., Sacks, M.S.: Finite element implementation of a generalized Fung-elastic constitutive model for planar soft tissues. Biomech. Model. Mechanobiol. 4(2–3), 190–199 (2005)

    Article  Google Scholar 

  37. 37.

    Sun, W., Sacks, M.S., Sellaro, T.L., Slaughter, W.S., Scott, M.J.: Biaxial mechanical response of bioprosthetic heart valve biomaterials to high in-plane shear. J. Biomech. Eng. 125(3), 372–380 (2003)

    Article  Google Scholar 

  38. 38.

    Huang, S. and Huang, H.-Y.S. Virtual Experiments of Heart Valve Tissue. IEEE Engineering in Medicine and Biology Society, pp. 6645–6648 (IEEE, San Diego, CA, 2012).

  39. 39.

    Huang, S. and Huang, H.-Y.S. Tissue- and cell-levels stress distribution of heart valve tissue during diastole. Proceedings of the ASME International Mechanical Engineering Congress and Exposition, (2013).

  40. 40.

    Nye, J.F. Physical properties of crystals, their representation by tensors and matrices. Oxford, Clarendon Press (1957).

  41. 41.

    Slaughter, W.S.: The Linearized Theory of Elasticity. Birkhauser, Boston (2001)

    Google Scholar 

  42. 42.

    Zhao, R.G., Wyss, K., Simmons, C.A.: Comparison of analytical and inverse finite element approaches to estimate cell viscoelastic properties by micropipette aspiration. J. Biomech. 42(16), 2768–2773 (2009)

    Article  Google Scholar 

  43. 43.

    Huang, H.-Y.S., Balhouse, B.N. and Huang, S. A Synergy Study of Heart Valve Tissue Mechanics, Microstructures, and Collagen Concentration. 2012 ASME International Mechanical Engineering Congress and Exposition ASME, Houston (2012)

  44. 44.

    David, H., Boughner, D.R., Vesely, I., Gerosa, G.: The pulmonary valve. Is it mechanically suitable for use as an aortic valve replacement? ASAIO J. 40(2), 206–212 (1994)

    Article  Google Scholar 

  45. 45.

    Lanir, Y.: A structural theory for the homogeneous biaxial stress–strain relationships in flat collagenous tissues. J. Biomech. 12(6), 423–436 (1979)

    Article  Google Scholar 

  46. 46.

    Lanir, Y.: Constitutive equations for fibrous connective tissues. J. Biomech. 16(1), 1–12 (1983)

    Article  Google Scholar 

  47. 47.

    Lanir, Y.: A microstructure model for the rheology of mammalian tendon. ASME Journal of Biomechanical Engineering, 102(4), 332–339 (1980)

  48. 48.

    Lanir, Y.: Plausibility of structural constitutive equations for isotropic soft tissue in finite static deformations. J. Appl. Mech. 61, 695–702 (1994)

    ADS  Article  MATH  Google Scholar 

  49. 49.

    Sacks, M.S., Schoen, F.J.: Collagen fiber disruption occurs independent of calcification in clinically explanted bioprosthetic heart valves. J. Biomed. Mater. Res. 62(3), 359–371 (2002)

    Article  Google Scholar 

  50. 50.

    Perron, J., Moran, A.M., Gauvreau, K., del Nido, P.J., Mayer, J.E., Jonas, R.A.: Valved homograft conduit repair of the right heart in early infancy. Ann. Thorac. Surg. 68(2), 542–548 (1999)

    Article  Google Scholar 

  51. 51.

    Stella, J.A., Sacks, M.S.: On the biaxial mechanical properties of the layers of the aortic valve leaflet. J. Biomech. Eng.-Trans. ASME 129(5), 757–766 (2007)

    Article  Google Scholar 

  52. 52.

    Gupta, V., Tseng, H., Lawrence, B.D., Grande-Allen, K.J.: Effect of cyclic mechanical strain on glycosaminoglycan and proteoglycan synthesis by heart valve cells. Acta Biomater. 5(2), 531–540 (2009)

    Article  Google Scholar 

  53. 53.

    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. 71(3), 548–556 (2006)

    Article  Google Scholar 

  54. 54.

    Smith, K.E., Metzler, S.A., Warnock, J.N.: Cyclic strain inhibits acute pro-inflammatory gene expression in aortic valve interstitial cells. Biomech. Model. Mechanobiol. 9(1), 117–125 (2010)

    Article  Google Scholar 

  55. 55.

    Throm Quinlan, A.M., Sierad, L.N., Capulli, A.K., Firstenberg, L.E., Billiar, K.L.: Combining dynamic stretch and tunable stiffness to probe cell mechanobiology in vitro. PLoS ONE 6(8), e23272 (2011)

    ADS  Article  Google Scholar 

  56. 56.

    Carruthers, C.A., Alfieri, C.M., Joyce, E.M., Watkins, S.C., Yutzey, K.E., Sacks, M.S.: Gene expression and collagen fiber micromechanical interactions of the semilunar heart valve interstitial cell. Cell. Mol. Bioeng. 5(3), 254–265 (2012)

    Article  Google Scholar 

  57. 57.

    Stella, J.A., Liao, J., Sacks, M.S.: Time-dependent biaxial mechanical behavior of the aortic heart valve leaflet. J. Biomech. 40(14), 3169–3177 (2007)

    Article  Google Scholar 

  58. 58.

    Merryman, W.D., Bieniek, P.D., Guilak, F. and Sacks, M.S. Viscoelastic Properties of the Aortic Valve Interstitial Cell. J. Biomech. Eng. 131(4), 041005 (2009)

  59. 59.

    Merryman, W.D., Youn, I., Lukoff, H.D., Krueger, P.M., Guilak, F., Hopkins, R.A., Sacks, M.S.: Correlation between heart valve interstitial cell stiffness and transvalvular pressure: implications for collagen biosynthesis. Am. J. Physiol.-Heart Circ. Physiol. 290(1), H224–H231 (2006)

    Article  Google Scholar 

  60. 60.

    Rabkin-Aikawa, E., Aikawa, M., Farber, M., Kratz, J.R., Garcia-Cardena, G., Kouchoukos, N.T., Mitchell, M.B., Jonas, R.A., Schoen, F.J.: Clinical pulmonary autograft valves: pathologic evidence of adaptive remodeling in the aortic site. J. Thorac. Cardiovasc. Surg. 128(4), 552–561 (2004)

    Article  Google Scholar 

  61. 61.

    Latif, N., Sarathchandra, R., Taylor, R.M., Antoniw, J., Yacoub, M.H.: Molecules mediating cell-ECM and cell-cell communication in human heart valves. Cell Biochem. Biophys. 43(2), 275–287 (2005)

    Article  Google Scholar 

  62. 62.

    Gu, X., Masters, K.S.: Regulation of valvular interstitial cell calcification by adhesive peptide sequences. J. Biomed. Mater. Res. A 93(4), 1620–1630 (2010)

    Google Scholar 

  63. 63.

    Huang, H.-Y.S., Huang, S., Frazier, Colin P., Prim, Peter, and Harrysson, O., Directional Mechanical Property of Porcine Skin Tissues. J. Mech. Med. Biol. 14(5), (2014). doi: 10.1142/S0219519414500699.

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Acknowledgments

The studies presented herein were supported by start-up funds provided by the North Carolina State University Department of Mechanical and Aerospace Engineering.

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None declared.

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The studies presented herein were supported by start-up funds provided by the North Carolina State University Department of Mechanical and Aerospace Engineering.

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Correspondence to Hsiao-Ying Shadow Huang.

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Huang, S., Huang, HY.S. Prediction of matrix-to-cell stress transfer in heart valve tissues. J Biol Phys 41, 9–22 (2015). https://doi.org/10.1007/s10867-014-9362-z

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Keywords

  • Finite element method
  • Heart valve tissues
  • Biomechanics
  • Stress analysis
  • Collagen fiber orientation
  • Tissue engineering