Skip to main content
Log in

Rapid vascularization of tissue-engineered vascular grafts in vivo by endothelial cells in co-culture with smooth muscle cells

  • Published:
Journal of Materials Science: Materials in Medicine Aims and scope Submit manuscript

Abstract

A major challenge facing the development of tissue-engineered vascular grafts (TEVGs), promising living replacements for diseased vascular structures, is enhancing angiogenesis. To promote rapid vascularization, endothelial cells (ECs) were co-cultured with smooth muscle cells (SMCs) in decellularized small intestinal submucosa scaffolds to regenerate angiogenic-TEVGs (A-TEVGs). Observation of the A-TEVGs at 1 month post-implantation revealed that a rich network of neocapillaries lining the blood vessel wall had developed; that the ECs of the neovasculatures had been derived from previously seeded ECs and later invading ECs of the host’s vascular bed; that tissue vascularization had not significantly impaired mechanical properties; and that the maximal tensile strength of the A-TEVGs was of the same order of magnitude as that of native porcine femoral arteries. These results indicate that of the co-culturing of ECs with SMCs could enhance vascularization of TEVGs in vivo, possibly increasing graft perfusion and host integration.

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.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Tu JV, Pashos CL, Naylor CD, Chen E, Normand SL, Newhouse JP, McNeil BJ. Use of cardiac procedures and outcomes in elderly patients with myocardial infarction in the United States and Canada. N Engl J Med. 1997;336:1500–5.

    Article  CAS  Google Scholar 

  2. Niklason LE. Techview: medical technology. Replacement arteries made to order. Science. 1999;286:1493–4.

    CAS  Google Scholar 

  3. Tiwari A, Cheng KS, Salacinski H, Hamilton G, Seifalian AM. Improving the patency of vascular bypass grafts: the role of suture materials and surgical techniques on reducing anastomotic compliance mismatch. Eur J Vasc Endovasc Surg. 2003;25:287–95.

    Article  CAS  Google Scholar 

  4. Klinkert P, Post PN, Breslau PJ, van Bockel JH. Saphenous vein versus PTFE for above-knee femoropopliteal bypass. A review of the literature. Eur J Vasc Endovasc Surg. 2004;27:357–62.

    Article  CAS  Google Scholar 

  5. Zhang WJ, Liu W, Cui L, Cao Y. Tissue engineering of blood vessel. J Cell Mol Med. 2007;11:945–57.

    Article  CAS  Google Scholar 

  6. Cho SW, Lim SH, Kim IK, Hong YS, Kim SS, Yoo KJ, Park HY, Jang Y, Chang BC, Choi CY, Hwang KC, Kim BS. Small-diameter blood vessels engineered with bone marrow-derived cells. Ann Surg. 2005;241:506–15.

    Article  Google Scholar 

  7. Isenberg BC, Williams C, Tranquillo RT. Small-diameter artificial arteries engineered in vitro. Circ Res. 2006;98:25–35.

    Article  CAS  Google Scholar 

  8. Gong Z, Niklason LE. Small-diameter human vessel wall engineered from bone marrow-derived mesenchymal stem cells (hMSCs). Faseb J. 2008;22:1635–48.

    Article  CAS  Google Scholar 

  9. Wang C, Cen L, Yin S, Liu Q, Liu W, Cao Y, Cui L. A small diameter elastic blood vessel wall prepared under pulsatile conditions from polyglycolic acid mesh and smooth muscle cells differentiated from adipose-derived stem cells. Biomaterials. 2010;31:621–30.

    Article  Google Scholar 

  10. Griffith CK, Miller C, Sainson RC, Calvert JW, Jeon NL, Hughes CC, George SC. Diffusion limits of an in vitro thick prevascularized tissue. Tissue Eng. 2005;11:257–66.

    Article  CAS  Google Scholar 

  11. Tremblay PL, Hudon V, Berthod F, Germain L, Auger FA. Inosculation of tissue-engineered capillaries with the host’s vasculature in a reconstructed skin transplanted on mice. Am J Transplant. 2005;5:1002–10.

    Article  Google Scholar 

  12. Jain RK, Au P, Tam J, Duda DG, Fukumura D. Engineering vascularized tissue. Nat Biotechnol. 2005;23:821–3.

    Article  CAS  Google Scholar 

  13. Linke K, Schanz J, Hansmann J, Walles T, Brunner H, Mertsching H. Engineered liver-like tissue on a capillarized matrix for applied research. Tissue Eng. 2007;13:2699–707.

    Article  CAS  Google Scholar 

  14. Ryu W, Min SW, Hammerick KE, Vyakarnam M, Greco RS, Prinz FB, Fasching RJ. The construction of three-dimensional micro-fluidic scaffolds of biodegradable polymers by solvent vapor based bonding of micro-molded layers. Biomaterials. 2007;28:1174–84.

    Article  CAS  Google Scholar 

  15. Nillesen ST, Geutjes PJ, Wismans R, Schalkwijk J, Daamen WF, van Kuppevelt TH. Increased angiogenesis and blood vessel maturation in acellular collagen-heparin scaffolds containing both FGF2 and VEGF. Biomaterials. 2007;28:1123–31.

    Article  CAS  Google Scholar 

  16. Ott HC, Matthiesen TS, Goh SK, Black LD, Kren SM, Netoff TI, Taylor DA. Perfusion-decellularized matrix: using nature’s platform to engineer a bioartificial heart. Nat Med. 2008;14:213–21.

    Article  CAS  Google Scholar 

  17. Hofmann A, Ritz U, Verrier S, Eglin D, Alini M, Fuchs S, et al. The effect of human osteoblasts on proliferation and neo-vessel formation of human umbilical vein endothelial cells in a long-term 3D co-culture on polyurethane scaffolds. Biomaterials. 2008;29:4217–26.

    Article  CAS  Google Scholar 

  18. Huang HM, Wu SF, Ren H. Tissue-engineered graft constructed by self-derived cells and heterogeneous acellular matrix. J Zhejiang Univ Sci B. 2006;7:351–6.

    Article  CAS  Google Scholar 

  19. Liu Y, Bharadwaj S, Lee SJ, Atala A, Zhang Y. Optimization of a natural collagen scaffold to aid cell-matrix penetration for urologic tissue engineering. Biomaterials. 2009;30:3865–73.

    Article  CAS  Google Scholar 

  20. Eiselt P, Kim BS, Chacko B, Isenberg B, Peters MC, Greene KG, et al. Development of technologies aiding large-tissue engineering. Biotechnol Prog. 1998;14:134–40.

    Article  CAS  Google Scholar 

  21. Muschler GF, Nakamoto C, Griffith LG. Engineering principles of clinical cell-based tissue engineering. J Bone Joint Surg Am. 2004;86–A:1541–58.

  22. Kaully T, Kaufman-Francis K, Lesman A, Levenberg S. Vascularization—the conduit to viable engineered tissues. Tissue Eng Part B Rev. 2009;15:159–69.

    Article  CAS  Google Scholar 

  23. Nillesen ST, Geutjes PJ, Wismans R, Schalkwijk J, Daamen WF, van Kuppevelt TH. Increased angiogenesis and blood vessel maturation in acellular collagen-heparin scaffolds containing both FGF2 and VEGF. Biomaterials. 2007;28:1123–31.

    Article  CAS  Google Scholar 

  24. Zhang H, Hayashi T, Tsuru K, Deguchi K, Nagahara M, Hayakawa S, Nagai M, Kamiya T, Osaka A, Abe K. Vascular endothelial growth factor promotes brain tissue regeneration with a novel biomaterial polydimethylsiloxane-tetraethoxysilane. Brain Res. 2007;1132:29–35.

    Article  CAS  Google Scholar 

  25. Ennett AB, Kaigler D, Mooney DJ. Temporally regulated delivery of VEGF in vitro and in vivo. J Biomed Mater Res A. 2006;79:176–84.

    Google Scholar 

  26. Kaigler D, Wang Z, Horger K, Mooney DJ, Krebsbach PH. VEGF scaffolds enhance angiogenesis and bone regeneration in irradiated osseous defects. J Bone Miner Res. 2006;21:735–44.

    Article  CAS  Google Scholar 

  27. Ghanaati S, Fuchs S, Webber MJ, Orth C, Barbeck M, Gomes ME, Reis RL, Kirkpatrick CJ. Rapid vascularization of starch-poly(caprolactone) in vivo by outgrowth endothelial cells in co-culture with primary osteoblasts. J Tissue Eng Regen Med. 2011;5:e136–43.

    Article  CAS  Google Scholar 

  28. Fuchs S, Ghanaati S, Orth C, Barbeck M, Kolbe M, Hofmann A, Eblenkamp M, Gomes M, Reis RL, Kirkpatrick CJ. Contribution of outgrowth endothelial cells from human peripheral blood on in vivo vascularization of bone tissue engineered constructs based on starch polycaprolactone scaffolds. Biomaterials. 2009;30:526–34.

    Article  CAS  Google Scholar 

  29. Fuchs S, Jiang X, Schmidt H, Dohle E, Ghanaati S, Orth C, Hofmann A, Motta A, Migliaresi C, Kirkpatrick CJ. Dynamic processes involved in the pre-vascularization of silk fibroin constructs for bone regeneration using outgrowth endothelial cells. Biomaterials. 2009;30:1329–38.

    Article  CAS  Google Scholar 

  30. Kirkpatrick CJ, Fuchs S, Unger RE. Co-culture systems for vascularization—learning from nature. Adv Drug Deliv Rev. 2011;63:291–9.

    Article  CAS  Google Scholar 

  31. L’Heureux N, Dusserre N, Konig G, Victor B, Keire P, Wight TN, Chronos NA, Kyles AE, Gregory CR, Hoyt G, Robbins RC, McAllister TN. Human tissue-engineered blood vessels for adult arterial revascularization. Nat Med. 2006;12:361–5.

    Article  Google Scholar 

  32. Guillemette MD, Gauvin R, Perron C, Labbé R, Germain L, Auger FA. Tissue-engineered vascular adventitia with vasa vasorum improves graft integration and vascularization through inosculation. Tissue Eng Part A. 2010;16:2617–26.

    Article  CAS  Google Scholar 

  33. McKee JA, Banik SS, Boyer MJ, Hamad NM, Lawson JH, Niklason LE, Counter CM. Human arteries engineered in vitro. EMBO Rep. 2003;4:633–8.

    Article  CAS  Google Scholar 

  34. Fiala R, Vidlar A, Vrtal R, Belej K, Student V. Porcine small intestinal submucosa graft for repair of anterior urethral strictures. Eur Urol. 2007;51:1702–8.

    Article  Google Scholar 

  35. Feng C, Xu YM, Fu Q, Zhu WD, Cui L, Chen J. Evaluation of the biocompatibility and mechanical properties of naturally derived and synthetic scaffolds for urethral reconstruction. J Biomed Mater Res A. 2010;94:317–25.

    Google Scholar 

  36. Wu S, Liu Y, Bharadwaj S, Atala A, Zhang Y. Human urine-derived stem cells seeded in a modified 3D porous small intestinal submucosa scaffold for urethral tissue engineering. Biomaterials. 2011;32:1317–26.

    Article  Google Scholar 

  37. Gossl M, Malyar NM, Rosol M, Beighley PE, Ritman EL. Impact of coronary vasa vasorum functional structure on coronary vessel wall perfusion distribution. Am J Physiol Heart Circ Physiol. 2003;285:H2019–26.

    CAS  Google Scholar 

  38. Borges J, Muller MC, Momeni A, Stark GB, Torio-Padron N. In vitro analysis of the interactions between preadipocytes and endothelial cells in a 3D fibrin matrix. Minim Invasive Ther Allied Technol. 2007;16:141–8.

    Article  Google Scholar 

  39. Wyatt AP, Rothnie NG, Taylor GW. The vascularization of vein-grafts. Br J Surg. 1964;51:378–81.

    Article  CAS  Google Scholar 

  40. Guillemette MD, Gauvin R, Perron C, Labbe R, Germain L, Auger FA. Tissue-engineered vascular adventitia with vasa vasorum improves graft integration and vascularization through inosculation. Tissue Eng Part A. 2010;16:2617–26.

    Article  CAS  Google Scholar 

  41. Koike N, Fukumura D, Gralla O, Au P, Schechner JS, Jain RK. Tissue engineering: creation of long-lasting blood vessels. Nature. 2004;428:138–9.

    Article  CAS  Google Scholar 

  42. Zisch AH. Tissue engineering of angiogenesis with autologous endothelial progenitor cells. Curr Opin Biotechnol. 2004;15:424–9.

    Article  CAS  Google Scholar 

  43. Chen X, Aledia AS, Popson SA, Him L, Hughes CC, George SC. Rapid anastomosis of endothelial progenitor cell-derived vessels with host vasculature is promoted by a high density of cotransplanted fibroblasts. Tissue Eng Part A. 2010;16:585–94.

    Article  CAS  Google Scholar 

Download references

Acknowledgments

We thank Dr. Shaofeng Wu of the Department of Pediatric Urology, Shanghai Children’s Medical Center, Shanghai Jiaotong University, School of Medicine, for sharing his expertise in the preparation of decellularized SIS scaffolds. This present work was funded by a grant from the National Natural Science Foundation of China (No. 81170151) and a grant from the R&D Project of Combination Medicine and Engineering at Shanghai Jiaotong University (No. YG2010MS63).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Huimin Huang.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wang, Z., He, Y., Yu, X. et al. Rapid vascularization of tissue-engineered vascular grafts in vivo by endothelial cells in co-culture with smooth muscle cells. J Mater Sci: Mater Med 23, 1109–1117 (2012). https://doi.org/10.1007/s10856-012-4576-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10856-012-4576-8

Keywords

Navigation