Skip to main content
Log in

An Experimental Investigation of the Effect of Mechanical and Biochemical Stimuli on Cell Migration Within a Decellularized Vascular Construct

  • Published:
Annals of Biomedical Engineering Aims and scope Submit manuscript

Abstract

The goal of this study was to promote rapid repopulation of the medial layer of decellularized tissues for use as vascular grafts. We utilized a combined approach of biochemical and mechanical stimuli to enhance repopulation of decellularized porcine arterial tissue. Chitosan β-glycerophosphate loaded with hepatocyte growth factor (HGF) was injected into a channel in the artery wall while rat mesenchymal stem cells (rMSCs) were injected in two channels located 120° to this channel. In a second group rMSCs were injected into channels located at intervals of 120°. Both groups were subjected to 7 days mechanical stimuli in comparison to non-dynamically conditioned static controls. The combined effect of the biochemical and mechanical stimuli demonstrated that the repopulation zone was significantly enhanced, maximum migration achieved was 1.8 times more than that of the static HGF cultured control and 10 times higher than the average migration for statically cultured scaffolds without biochemical stimulus. Human umbilical vein endothelial cells were also successfully adhered to the scaffold and dynamically cultured. The response of medially injected cells to the biomechanically and biochemically altered environment demonstrated that enhanced circumferential scaffold repopulation could be achieved.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5

Similar content being viewed by others

References

  1. Bilodeau, K., F. Couet, F. Boccafoschi, and D. Mantovani. Design of a perfusion bioreactor specific to the regeneration of vascular tissues Under mechanical stresses. Artif. Organs 29:906–912, 2005. doi:10.1111/j.1525-1594.2005.00154.x.

    Article  PubMed  Google Scholar 

  2. Carmeliet, P., and E. M. Conway. Growing better blood vessels. Nat. Biotechnol. 19:1019–1020, 2001.

    Article  CAS  PubMed  Google Scholar 

  3. Chan-Park, M. B., et al. Biomimetic control of vascular smooth muscle cell morphology and phenotype for functional tissue-engineered small-diameter blood vessels. J. Biomed. Mater. Res. Part A 91A:629–634, 2009.

    Article  CAS  Google Scholar 

  4. Cho, S.-W., et al. Small-diameter blood vessels engineered with bone marrow-derived cells. Ann. Surg. 241:506–515, 2005.

    Article  PubMed Central  PubMed  Google Scholar 

  5. Couet, F., S. Meghezi, and D. Mantovani. Fetal development, mechanobiology and optimal control processes can improve vascular tissue regeneration in bioreactors: an integrative review. Med. Eng. Phys. 34:269–278, 2012. doi:10.1016/j.medengphy.2011.10.009.

    Article  PubMed  Google Scholar 

  6. Crapo, P. M., J. Gao, and Y. Wang. Seamless tubular poly(glycerol sebacate) scaffolds: high-yield fabrication and potential applications. J. Biomed. Mater. Res. Part A 86A:354–363, 2008. doi:10.1002/jbm.a.31598.

    Article  CAS  Google Scholar 

  7. Da Silva Meirelles, L., A. M. Fontes, D. T. Covas, and A. I. Caplan. Mechanisms involved in the therapeutic properties of mesenchymal stem cells. Cytokine Growth Factor Rev. 20:419–427, 2009. doi:10.1016/j.cytogfr.2009.10.002.

    Article  Google Scholar 

  8. Dahan, N., et al. Porcine small diameter arterial extracellular matrix supports endothelium formation and media remodeling forming a promising vascular engineered biograft. Tissue Eng. Part A 18:411–422, 2012.

    Article  CAS  PubMed  Google Scholar 

  9. Duffy, G. P., et al. Towards in vitro vascularisation of collagen-GAG scaffolds. Eur. Cell. Mater. 21:15–30, 2011.

    CAS  PubMed  Google Scholar 

  10. Farkouh, M. E., et al. Strategies for multivessel revascularization in patients with diabetes. N. Engl. J. Med. 367:2375–2384, 2012. doi:10.1056/NEJMoa1211585.

    Article  CAS  PubMed  Google Scholar 

  11. Forte, G., et al. Hepatocyte growth factor effects on mesenchymal stem cells: proliferation, migration, and differentiation. Stem Cells 24:23–33, 2006. doi:10.1634/stemcells.2004-0176.

    Article  CAS  PubMed  Google Scholar 

  12. Gong, Z., and L. E. Niklason. Small-diameter human vessel wall engineered from bone marrow-derived mesenchymal stem cells (hMSCs). FASEB J. 22:1635–1648, 2008. doi:10.1096/fj.07-087924.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  13. Grines, C. L., et al. A comparison of immediate angioplasty with thrombolytic therapy for acute myocardial infarction. N. Engl. J. Med. 328:673–679, 1993. doi:10.1056/NEJM199303113281001.

    Article  CAS  PubMed  Google Scholar 

  14. Hahn, M., M. McHale, E. Wang, R. Schmedlen, and J. West. Physiologic pulsatile flow bioreactor conditioning of poly(ethylene glycol)-based tissue engineered vascular grafts. Ann. Biomed. Eng. 35:190–200, 2007. doi:10.1007/s10439-006-9099-3.

    Article  PubMed  Google Scholar 

  15. Hastings, C. L., et al. Development of a thermoresponsive chitosan gel combined with human mesenchymal stem cells and desferrioxamine as a multimodal pro-angiogenic therapeutic for the treatment of critical limb ischaemia. J. Controlled Release 161:73–80, 2012.

    Article  CAS  Google Scholar 

  16. Hilbert, S. L., L. E. Boerboom, S. A. Livesey, and V. J. Ferrans. Explant pathology study of decellularized carotid artery vascular grafts. J. Biomed. Mater. Res. Part A 69A:197–204, 2004.

    Article  CAS  Google Scholar 

  17. Isenberg, B. C., C. Williams, and R. T. Tranquillo. Small-diameter artificial arteries engineered in vitro. Circ. Res. 98:25–35, 2006. doi:10.1161/01.res.0000196867.12470.84.

    Article  CAS  PubMed  Google Scholar 

  18. Koenneker, S., et al. A biological alternative to alloplastic grafts in dialysis therapy: evaluation of an autologised bioartificial hemodialysis shunt vessel in a sheep model. Eur. J. Vasc. Endovasc. Surg. 40:810–816, 2010. doi:10.1016/j.ejvs.2010.04.023.

    Article  CAS  PubMed  Google Scholar 

  19. L’Heureux, N., et al. Human tissue-engineered blood vessels for adult arterial revascularization. Nat. Med. 12:361–365, 2006.

    Article  PubMed Central  PubMed  Google Scholar 

  20. McCawley, L. J., and L. M. Matrisian. Matrix metalloproteinases: they’re not just for matrix anymore!. Curr. Opin. Cell Biol. 13:534–540, 2001. doi:10.1016/S0955-0674(00)00248-9.

    Article  CAS  PubMed  Google Scholar 

  21. McFetridge, P. S., K. Abe, M. Horrocks, and J. B. Chaudhuri. Vascular tissue engineering: bioreactor design considerations for extended culture of primary human vascular smooth muscle cells. ASAIO J. 53:623–630, 2007.

    Article  PubMed  Google Scholar 

  22. Mohr, F. W., et al. Coronary artery bypass graft surgery vs. percutaneous coronary intervention in patients with three-vessel disease and left main coronary disease: 5-year follow-up of the randomised, clinical SYNTAX trial. Lancet 381:629–638, 2013. doi:10.1016/S0140-6736(13)60141-5.

    Article  PubMed  Google Scholar 

  23. Moses, J. W., et al. Sirolimus-eluting stents vs. standard stents in patients with stenosis in a native coronary artery. N. Engl. J. Med. 349:1315–1323, 2003. doi:10.1056/NEJMoa035071.

    Article  CAS  PubMed  Google Scholar 

  24. Neuss, S., E. Becher, M. Wöltje, L. Tietze, and W. Jahnen-Dechent. Functional expression of HGF and HGF receptor/c-met in adult human Mesenchymal stem cells suggests a role in cell mobilization, tissue repair, and wound healing. Stem Cells 22:405–414, 2004. doi:10.1634/stemcells.22-3-405.

    Article  CAS  PubMed  Google Scholar 

  25. Niklason, L. E., et al. Functional arteries grown in vitro. Science 284:489–493, 1999.

    Article  CAS  PubMed  Google Scholar 

  26. O’Cearbhaill, E. D., M. Murphy, F. Barry, P. E. McHugh, and V. Barron. Behavior of human mesenchymal stem cells in fibrin-based vascular tissue engineering constructs. Ann. Biomed. Eng. 38:649–657, 2010.

    Article  PubMed  Google Scholar 

  27. Olausson, M., et al. Transplantation of an allogeneic vein bioengineered with autologous stem cells: a proof-of-concept study. The Lancet 380:230–237, 2012.

    Article  Google Scholar 

  28. Owens, G. K., M. S. Kumar, and B. R. Wamhoff. Molecular regulation of vascular smooth muscle cell differentiation in development and disease. Physiol. Rev. 84:767–801, 2004. doi:10.1152/physrev.00041.2003.

    Article  CAS  PubMed  Google Scholar 

  29. Reneman, R. S., T. Arts, and A. P. Hoeks. Wall shear stress—an important determinant of endothelial cell function and structure–in the arterial system in vivo. Discrepancies with theory. J. Vasc. Res. 43:251–269, 2006. doi:10.1159/000091648.

    Article  PubMed  Google Scholar 

  30. Serruys, P. W., et al. A comparison of balloon-expandable-stent implantation with balloon angioplasty in patients with coronary artery disease. N. Engl. J. Med. 331:489–495, 1994. doi:10.1056/NEJM199408253310801.

    Article  CAS  PubMed  Google Scholar 

  31. Sheridan, W. S., G. P. Duffy, and B. P. Murphy. Mechanical characterization of a customized decellularized scaffold for vascular tissue engineering. J. Mech. Behav. Biomed. Mater. 8:58–70, 2012.

    Article  CAS  PubMed  Google Scholar 

  32. Sluijter, J. P. G., D. P. V. de Kleijn, and G. Pasterkamp. Vascular remodeling and protease inhibition—bench to bedside. Cardiovasc. Res. 69:595–603, 2006. doi:10.1016/j.cardiores.2005.11.026.

    Article  CAS  PubMed  Google Scholar 

  33. Tayalia, P., and D. J. Mooney. Controlled growth factor delivery for tissue engineering. Adv. Mater. 21:3269–3285, 2009. doi:10.1002/adma.200900241.

    Article  CAS  PubMed  Google Scholar 

  34. Villalona, G. A., et al. Cell-seeding techniques in vascular tissue engineering. Tissue Eng. Part B 16:341–350, 2010. doi:10.1089/ten.TEB.2009.0527.

    Article  Google Scholar 

  35. Williams, C., and T. M. Wick. Perfusion bioreactor for small diameter tissue-engineered arteries. Tissue Eng. 10:930–941, 2004. doi:10.1089/1076327041348536.

    Article  CAS  PubMed  Google Scholar 

  36. Williams, C., et al. Altered structural and mechanical properties in decellularized rabbit carotid arteries. Acta Biomater. 5:993–1005, 2009.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  37. Yazdani, S. K., et al. Smooth muscle cell seeding of decellularized scaffolds: the importance of bioreactor preconditioning to development of a more native architecture for tissue-engineered blood vessels. Tissue Eng. Part A 15:827–840, 2009. doi:10.1089/ten.tea.2008.0092.

    Article  CAS  PubMed  Google Scholar 

  38. Zhao, Y., et al. The development of a tissue-engineered artery using decellularized scaffold and autologous ovine mesenchymal stem cells. Biomaterials 31:296–307, 2010.

    Article  PubMed  Google Scholar 

Download references

Conflict of Interest

The authors have no conflicts of interest with respect to this study.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Bruce P. Murphy.

Additional information

Associate Editor Jane Grande-Allen oversaw the review of this article.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sheridan, W.S., Ryan, A.J., Duffy, G.P. et al. An Experimental Investigation of the Effect of Mechanical and Biochemical Stimuli on Cell Migration Within a Decellularized Vascular Construct. Ann Biomed Eng 42, 2029–2038 (2014). https://doi.org/10.1007/s10439-014-1063-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10439-014-1063-z

Keywords

Navigation