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Multiscale Modeling in Vascular Disease and Tissue Engineering

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Multiscale Computer Modeling in Biomechanics and Biomedical Engineering

Part of the book series: Studies in Mechanobiology, Tissue Engineering and Biomaterials ((SMTEB,volume 14))

Abstract

The human body, and hence the vascular system, is by its very nature a dynamic multiscale hierarchial system. This multiscale nature encompasses different length scales, from molecular and cellular levels to the tissue and organ level, as well as different physical phenomena, such as mechanical, biological and chemical processes. In arteries, vascular cells alter their growth, phenotype and extracellular matrix production in response to macro mechanical changes. These cell level events can in turn accumulate and emerge at the tissue level as pathological conditions such as atherosclerosis and intimal hyperplasia. These cardiovascular diseases evolve through adaptation of cells and tissues over days to months also demonstrating the multiscale nature of vascular diseases with respect to time. The challenge in vascular multiscale modelling is to create a framework which can incorporate the key mechanical, biological and chemical characteristics of this complex system at these various space and time scales to successfully capture the long-term behaviour of the system. Such a framework can then be used to gain additional insights with regards to pathological conditions within the vascular system and to improve the design of medical devices used to treat such pathologies. In the following chapter, a review will be presented of some relevant studies reported in literature which have used multiscale modelling approaches to elucidate the growth and remodelling mechanisms underlying vascular diseases, such as atherosclerosis, in-stent restenosis and intimal hyperplasia.

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References

  1. Mi, Q., Riviere, B., Clermont, G., Steed, DL., Vodovotz, Y. (2007) Agent-based model of inflammation and wound healing: insights into diabetic foot ulcer pathology and the role of transforming growth factor-b1. Wound Rep. Reg. 15, 671–682

    Google Scholar 

  2. Li, N.Y.K., Verdolini, K., Clermont, G., Mi, Q., Rubinstein, E.N., et al.: A patient-specific in silico model of inflammation and healing tested in acute vocal fold injury. PLoS ONE 3(7), e2789 (2008). doi:10.1371/journal.pone.0002789

    Article  Google Scholar 

  3. Pappalardo, F., Cincotti, A., Motta, A., Pennisi, M.: Agent based modeling of atherosclerosis: a concrete help in personalized treatments. ICIC 2009, LNAI 5755, pp. 386–396 (2009)

    Google Scholar 

  4. Caiazzo, A., et al.: Towards a complex automata multiscale model of in-stent restenosis. In: Allen, G., Nabrzyski, J.,VanAlbada, G.D., Sloot, P.M.A. (eds.) Computational Science—Iccs, Part I, vol. 5544, pp. 705–714. Springer, Berlin (2009)

    Google Scholar 

  5. Tahir, H., Hoekstra, A.G., Lorenz, E., Lawford, P.V., Hose, D.R., Gunn, J., Evans, D.J.W.: Multi-scale simulations of the dynamics of in-stent restenosis: impact of stent deployment and design. Interface Focus 1(3), 365–373 (2011). doi:10.1098/rsfs.2010.0024

    Article  Google Scholar 

  6. Boyle, C.J., Lennon, A.B., Early, M., Kelly, D.J., Lally, C., Prendergast, P.J.: Computational simulation methodologies for mechanobiological modelling: a cell-centred approach to neointima development in stents. Philos. Trans. R. Soc. A Math. Phys. Eng. Sci. 368, 2919–2935 (2010). doi:10.1098/rsta.2010.0071

    Article  Google Scholar 

  7. Boyle, C.J., Lennon, A.B., Prendergast, P.J.: In silico prediction of the mechanobiological response of arterial tissue: application to angioplasty and stenting. J. Biomech. Eng. 133(8), 081001 (2011). doi:10.1115/1.4004492

    Article  Google Scholar 

  8. Zahedmanesh, H., Cahill, P.A., Lally, C.: Vascular stent design optimisation using numerical modelling techniques. In: Naik, G.R. (ed.) Applied Biological Engineering; Principles and Practice. InTech, ISBN 978-953-51-0412-4 (2012). doi:10.5772/37357

  9. Budu-Grajdeanu, P., Schugart, R.C., Friedman, A., Valentine, C., Agarwal, A.K., Rovin, B.H.: A mathematical model of venous neointimal hyperplasia formation. Theor. Biol. Med. Model. 5, 2 (2008). doi:10.1186/1742-4682-5-2

    Article  Google Scholar 

  10. Zahedmanesh, H., Lally, C.: A multiscale mechanobiological model using agent based models, application to vascular tissue engineering. Biomech. Model. Mechanobiol. 11, 363–377 (2012). doi:10.1007/s10237-011-0316-0

    Article  Google Scholar 

  11. Migliavacca, F., Petrini, L., Colombo, M., Auricchio, F., Pietrabissa, R.: Mechanical behavior of coronary stents investigated through the finite element method. J. Biomech. 35, 803–811 (2002)

    Article  Google Scholar 

  12. Lally, C., Dolan, F., Prendergast, P.J.: Cardiovascular stent design and vessel stresses: a finite element analysis. J. Biomech. 38, 1574–1581 (2005). doi:10.1016/j.jbiomech.2004.07.022

    Article  Google Scholar 

  13. Bedoya, J., Meyer, C.A., Timmins, L.H., Moreno, M.R., Moore Jr, J.E.: Effects of stent design parameters on normal artery wall mechanics. J. Biomech. Eng. 128(5), 757–765 (2006)

    Article  Google Scholar 

  14. Zahedmanesh, H., Lally, C.: Determination of the influence of stent strut thickness using the finite element method: implications for vascular injury and in-stent restenosis. Med. Biol. Eng. Comput. 47, 385–393 (2009). doi:10.1007/s11517-009-0432-5

    Article  Google Scholar 

  15. Zahedmanesh, H., Kelly, D., Lally, C.: Simulation of a balloon expandable stent in a realistic coronary artery, determination of the optimum modelling strategy. J. Biomech. 43, 2126–2132 (2010). doi:10.1016/j.jbiomech.2010.03.050

    Article  Google Scholar 

  16. Steinberg, D.: Thematic review series: the pathogenesis of atherosclerosis: an interpretive history of the cholesterol controversy, part III: mechanistically defining the role of hyperlipidemia. J. Lipid Res. 46, 2037–2051 (2005)

    Article  Google Scholar 

  17. Vukovic, I., Arsenijevic, N., Lackovic, V., Todorovic, V.: The origin and differentiation potential of smooth muscle cells in coronary atherosclerosis. Exp. Clin. Cardiol. 11(2), 123–128 (2006)

    Google Scholar 

  18. Kleemann, R., Zadelaar, S., Kooistra, T.: Cytokines and atherosclerosis: a comprehensive review of studies in mice. Cardiovasc. Res. 79, 360–376 (2008). doi:10.1093/cvr/cvn120

    Article  Google Scholar 

  19. Di Tomaso, G., Díaz-Zuccarini, V., Pichardo-Almarza, C.: A multiscale model of atherosclerotic plaque formation at its early stage. IEEE Trans. Biomed. Eng. 58(12), 3460–3463 (2011)

    Article  Google Scholar 

  20. Wieneke, H., Haude, M., Knocks, M., Gutersohn, A., von Birgelen, C., Baumgart, D., Erbel, R.: Evaluation of coronary stents in the animal model: a review. Materialwiss. Werkstofftech. 30, 809–813 (1999). doi:10.1002/(SICI)1521-4052(199912

    Article  Google Scholar 

  21. Babapulle, M.N., Eisenberg, M.J.: Coated stents for the prevention of restenosis: part I. Circulation 106, 2859–2866 (2002). doi:10.1161/01.CIR.0000038982.49640.70

    Article  Google Scholar 

  22. Welt, F.G., Rogers, C.: Inflammation and restenosis in the stent era. Arterioscler. Thromb. Vasc. Biol. 22(11), 1769–1776 (2002). doi:10.1161/01.ATV.0000037100.44766.5B

    Article  Google Scholar 

  23. Mitra, A.K., Agrawal, D.K.: In stent restenosis: bane of the stent era. J. Clin. Pathol. 59, 232–239 (2005). doi:10.1136/jcp.2005.025742

    Article  Google Scholar 

  24. Thyberg, J., Blomgren, K., Roy, J., Tran, P.K., Hedin, A.: Phenotype modulation of smooth muscle cells after arterial injury is associated with changes in the distribution of laminin and fibronectin. J. Histochem. Cytochem. 45, 837–846 (1997). doi:10.1177/002215549704500608

    Article  Google Scholar 

  25. Hirose, M., Kosugi, H., Nakazato, K., Hayashi, T.: Restoration to a quiescent and contractile phenotype from a proliferative phenotype of myofibroblasts-like human aortic smooth muscle cells by culture on type IV collagen gels. J. Biochem. 125, 991–1000 (1999)

    Article  Google Scholar 

  26. Aguilera, C.V., George, S.J., Johnson, J.L., Newby, A.C.: Relationship between type IV collagen degradation, metalloproteinase activity and smooth muscle cell migration and proliferation in cultured human saphenous vein. Cardiovasc. Res. 58, 679–688 (2003). doi:10.1016/S0008-6363(03)00256-6

    Article  Google Scholar 

  27. Monaco, S., Sparano, V., Gioia, M., Spardella, D., Di Pierro, D., Marini, S., Coletta, M.: Enzymatic processing of collagen IV by MMP-2 (gelatinase A) affects neutrophil migration and it is modulated by extracatalytic domains. Protein Sci. 15, 2805–2815 (2006). doi:10.1110/ps.062430706

    Article  Google Scholar 

  28. Adiguzel, E., Ahmad, P.J., Franco, C., Bendeck, M.P.: Collagens in the progression and complications of atherosclerosis. Vasc. Med. 14, 73–89 (2009). doi:10.1177/1358863X08094801

    Article  Google Scholar 

  29. Newby, A.C.: Matrix metalloproteinases regulate migration, proliferation, and death of vascular smooth muscle cells by degrading matrix and non-matrix substrates. Cardiovasc. Res. 69(3), 614–624 (2006). doi:10.1016/j.cardiores.2005.08.002

    Article  Google Scholar 

  30. Doronzo, G., Russo, I., Mattiello, L., Trovati, M., Anfossi, G.: Homocysteine rapidly increases matrix metalloproteinase-2 expression and activity in cultured human vascular smooth muscle cells. Thromb. Haemost. 94(6), 1285–1293 (2005). doi:10.1160/TH05040221

    Google Scholar 

  31. James, T.W., Wagner, R., White, L.A., Zwolak, R.M., Brinkerhoff, C.E.: Induction of collagenase gene expression by mechanical injury in avascular smooth muscle cell derived cell line. J. Cell. Physiol. 157, 426–437 (1993). doi:10.1002/jcp.1041570227

    Article  Google Scholar 

  32. Bendeck, M.P., Zempo, N., Clowes, A.W., Galardy, R.E.: Smooth muscle cell migration and matrix metalloproteinase expression after arterial injury in the rat. Circ. Res. 75, 539–545 (1994). doi:10.1161/01.RES.75.3.539

    Article  Google Scholar 

  33. Southgate, K.M., Fisher, M., Banning, A.P., Thurston, V.J., Baker, A.H., Fabunmi, R.P., Groves, P.H., Davies, M., Newby, A.C.: Upregulation of basement-membrane-degrading metalloproteinase secretion following balloon angioplasty of pig carotid arteries. Circ. Res. 79, 1177–1187 (1996). doi:10.1161/01.RES.79.6.1177

    Article  Google Scholar 

  34. George, S.J., Zaltsman, A.B., Newby, A.C.: Surgical preparative injury and neointima formation increase MMP-9 expression and MMP-2 activation in human saphenous vein. Cardiovasc. Res. 33, 447–459 (1997). doi:10.1016/S0008-6363(96)00211-8

    Article  Google Scholar 

  35. Asanuma, K., Magid, R., Johnson, C., Nerem, R.M., Galis, Z.: Uniaxial strain upregulates matrix-degrading enzymes produced by human vascular smooth muscle cells. Am. J. Physiol. Heart Circ. Physiol. 284, 1778–1784 (2003). doi:10.1152/ajpheart004942002

    Google Scholar 

  36. Grote, K., Flach, I., Luchtefeld, M., Akin, E., Holland, S.M., Drexler, H., Schieffer, B.: Mechanical stretch enhances mRNA expression and proenzyme release of matrix metalloproteinase- 2 (MMP-2) via NAD(P)H oxidase-derived reactive oxygen species. Circ. Res. 92, 80e–86e (2003). doi:10.1161/01.RES.0000077044.601387C

    Article  Google Scholar 

  37. Kornowski, R., Hong, M.K., Tio, F.O., Bramwell, O., Wu, H., Leon, M.B.: In-stent restenosis: contributions of inflammatory responses and arterial injury to neointimal hyperplasia. J. Am. Coll. Cardiol. 31(1), 224–230 (1998). doi:10.1016/S0735-1097(97)00450-6

    Article  Google Scholar 

  38. Gunn, J., Chan, K.H., Shepherd, L., Cumberland, D.C., Crossman, D.C.: Coronary artery stretch versus deep injury in the development of in-stent neointima. Heart 88, 401–405 (2002). doi:10.1136/heart.88.4.401

    Article  Google Scholar 

  39. Lowe, H.C., Oesterle, S.N., Khachigian, L.M.: Coronary in-stent restenosis: current status and future strategies. J. Am. Coll. Cardiol. 39, 183–193 (2002). doi:10.1016/S0735-1097(01)01742-9

    Article  Google Scholar 

  40. Houbballah, R., Robaldo, A., Albadawi, H., Titus, J., LaMuraglia, G.M.: A novel model of accelerated intimal hyperplasia in the pig iliac artery. Int. J. Exp. Pathol. 92, 422–427 (2011). doi:10.1111/j.13652613.2011.00790.x

    Article  Google Scholar 

  41. Kastrati, A., Mehilli, J., Dirschinger, J., Dotzer, F., Schühlen, H., Neumann, F.J., Fleckenstein, M., Pfafferott, C., Seyfarth, M., Schömig, A.: Intracoronary stenting and angiographic results: strut thickness effect on restenosis outcome (ISARSTEREO) trial. Circulation 103, 2816–2821 (2001). doi:10.1016/S0735-1097(03)00119-0

    Article  Google Scholar 

  42. Briguori, C., Sarais, C., Pagnotta, P.: In-stent restenosis in small coronary arteries: impact of strut thickness. J. Am. Coll. Cardiol. 40, 403–409 (2002). doi:10.1016/S0735-1097(02)01989-7

    Article  Google Scholar 

  43. Pache, J., Kastrati, A., Mehilli, J., Schühlen, H., Dotzer, F., Hausleiter, J., Fleckenstein, M., Neumann, F.J., Sattelberger, U., Schmitt, C., et al.: Intracoronary stenting and angiographic results: strut thickness effect on restenosis outcome (ISARSTEREO- 2), trial. J. Am. Coll. Cardiol. 41, 1283–1288 (2003). doi:10.1016/S0735-1097(03)00119-0

    Article  Google Scholar 

  44. Morton, A.C., Crossman, D., Gunn, J.: The influence of physical stent parameters upon restenosis. Pathol. Biol. 52, 196–205 (2004). doi:10.1016/j.patbio.2004.03.013

    Article  Google Scholar 

  45. Naito, Y., Shinoka, T., Duncan, D., Hibino, N., Solomon, D., Cleary, M., Rathore, A., Fein, C., Church, S., Breuer, C.: Vascular tissue engineering: towards the next generation vascular grafts. Adv. Drug Deliv. Rev. 63, 312–323 (2011)

    Article  Google Scholar 

  46. Chapman, G.B., Durante, W., Hellums, J.D., Schafer, A.I.: Physiological cyclic stretch causes cell cycle arrest in cultured vascular smooth muscle cells. Am. J. Physiol. Heart Circ. Physiol. 278, H748–H754 (2000)

    Google Scholar 

  47. Morrow, D., Sweeney, C., Birney, Y.A., Cummins, P.M., Walls, D., Redmond, E.M., Cahill, P.A.: Cyclic strain inhibits notch receptor signaling in vascular smooth muscle cells in vitro. Circ. Res. 96, 567–575 (2005). doi:10.1161/01.RES.0000159182.98874.43

    Article  Google Scholar 

  48. Kona, S., Chellamuthu, P., Xu, H., Hills, S.R., Nguyen, K.T.: Effects of cyclic strain and growth factors on vascular smooth muscle cell responses. Open Biomed. Eng. J. 3, 28–38 (2009). doi:10.2174/1874120700903010028

    Article  Google Scholar 

  49. Colombo, A., Guha, S., Mackle, J.N., Cahill, P.A., Lally, C.: Cyclic strain amplitude dictates the growth response of vascular smooth muscle cells in vitro: role in in-stent restenosis and inhibition with a sirolimus drug-eluting stent. Biomech. Model. Mechanobiol. (2012). doi:10.1007/s10237-012-0433-4

    Google Scholar 

  50. Buijs, J.O.D., Lu, L., Jorgensen, S.M., Dragomir-Daescu, D., Yaszemski, M.J., Ritman, E.L.: Solute transport in cyclically deformed porous tissue scaffolds with controlled pore cross-sectional geometries. Tissue Eng. Part A 15(8), 1989–1999 (2009). doi:10.1089/ten.tea.2008.0382

    Article  Google Scholar 

  51. Greisler, H.P., Joyce, K.A., Kim, D.U., Pham, S.M., Berceli, S.A., Borovetz, H.S.: Spatial and temporal changes in compliance following implantation of bioresorbable vascular grafts. J. Biomed. Mater. Res. 26, 1449–1461 (2004). doi:10.1002/jbm.820261105

    Article  Google Scholar 

  52. Song, Y., Wennink, J.W.H., Kamphuis, M.M.J., Sterk, L.M.T., Vermes, I., Poot, A.A., Feijen, J., Grijpma, D.W.: Dynamic culturing of smooth muscle cells in tubular poly (trimethylene carbonate) scaffolds for vascular tissue engineering. Tissue Eng. Part A (2010, in press). doi:10.1089/ten.tea.2009.0805

  53. Hahn, M.S., Mchale, M.K., Wang, E., Schmedlen, R.H., West, J.I.: Physiologic pulsatile flow bioreactor conditioning of poly(ethyleneglycol)-based tissue engineered vascular grafts. Ann. Biomed. Eng. 35(2), 190–200 (2007). doi:10.1007/s10439-006-9099-3

    Google Scholar 

  54. London, G.M., Marchais, S.J., Guerin, A.P., Pannier, B.: Arterial stiffness: pathophysiology and clinical impact. Clin. Exp. Hypertens. 26(7–8), 689–699 (2004)

    Article  Google Scholar 

  55. Jeong, S.I., Kwon, J.H., Lim, J.I., Cho, S.W., Jung, Y.M., Sung, W.J., Kim, S.H., Kim, Y.H., Lee, Y.M., Kim, B.S., Choi, C.Y., Kim, S.J.: Mechanoactive tissue engineering of vascular smooth muscle using pulsatile perfusion bioreactors and elastic PLCL scaffolds. Biomaterials 26, 1405–1411 (2005). doi:10.1016/j.biomaterials.2004.04.036

    Article  Google Scholar 

  56. Stankus, J.J., Guan, J., Fujimoto, K., Wagner, W.R.: Microintegrating smooth muscle cells in a biodegradable elastomeric fibre matrix. Biomaterials 27(5), 735–744 (2006). doi:10.1016/j.biomaterials.2005.06.020

    Article  Google Scholar 

  57. Creane, A., Maher, E., Sultan, S., Hynes, N., Kelly, D., Lally, C.: A remodelling metric for angular fibre distributions and its application to diseased carotid bifurcations. Biomech. Model. Mechanobiol. 11(6), 869–882 (2012)

    Article  Google Scholar 

  58. Zahedmanesh, H., Van Oosterwyck, H., Lally, C.: A multi-scale mechanobiological model of in-stent restenosis: deciphering the role of matrix metalloproteinase and extracellular matrix changes. Comput. Meth. Biomech. Biomed. Eng. (2012) doi:10.1080/10255842.2012.716830

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  1. School of Mechanical and Manufacturing Engineering, Dublin City University, Glasnevin, Dublin 9, Ireland

    Houman Zahedmanesh & Caitríona Lally

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  1. Houman Zahedmanesh
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  2. Caitríona Lally
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Correspondence to Caitríona Lally .

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  1. Tel Aviv University, Department of Biomedical Engineering, Faculty of Engineering, Tel Aviv, 69978, Israel

    Amit Gefen

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Zahedmanesh, H., Lally, C. (2013). Multiscale Modeling in Vascular Disease and Tissue Engineering. In: Gefen, A. (eds) Multiscale Computer Modeling in Biomechanics and Biomedical Engineering. Studies in Mechanobiology, Tissue Engineering and Biomaterials, vol 14. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8415_2012_159

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  • DOI: https://doi.org/10.1007/8415_2012_159

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