Biomedical Microdevices

, Volume 12, Issue 1, pp 71–79

Functional endothelialized microvascular networks with circular cross-sections in a tissue culture substrate

  • Jeffrey T. Borenstein
  • Malinda M. Tupper
  • Peter J. Mack
  • Eli J. Weinberg
  • Ahmad S. Khalil
  • James Hsiao
  • Guillermo García-Cardeña
Article

Abstract

Functional endothelialized networks constitute a critical building block for vascularized replacement tissues, organ assist devices, and laboratory tools for in vitro discovery and evaluation of new therapeutic compounds. Progress towards realization of these functional artificial vasculatures has been gated by limitations associated with the mechanical and surface chemical properties of commonly used microfluidic substrate materials and by the geometry of the microchannels produced using conventional fabrication techniques. Here we report on a method for constructing microvascular networks from polystyrene substrates commonly used for tissue culture, built with circular cross-sections and smooth transitions at bifurcations. Silicon master molds are constructed using an electroplating process that results in semi-circular channel cross-sections with smoothly varying radii. These master molds are used to emboss polystyrene sheets which are then joined to form closed bifurcated channel networks with circular cross-sections. The mechanical and surface chemical properties of these polystyrene microvascular network structures enable culture of endothelial cells along the inner lumen. Endothelial cell viability was assessed, documenting nearly confluent monolayers within 3D microfabricated channel networks with rounded cross-sections.

Keywords

Microfluidics Microfabrication Endothelial cells Vascular networks Polystyrene 

References

  1. S.N. Bhatia, C.S. Chen, Biomedical Microdevices 1, 131 (1999)CrossRefGoogle Scholar
  2. J.T. Borenstein, H. Terai, K.R. King, E.J. Weinberg, M.R. Kaazempur-Mofrad, J.P. Vacanti, Biomed Microdevices 4, 167 (2002)CrossRefGoogle Scholar
  3. K. A. Burgess, H.-H. Hu, W. R. Wagner, W. J. Federspiel, Biomedical Microdevices doi:10.1007/s10544-008-9215-2, (2008)
  4. J.P. Camp, T. Stokol, M.L. Shuler, Biomed Microdevices 10, 179–186 (2008)CrossRefGoogle Scholar
  5. A. Carraro, W.-M. Hsu et al., Biomedical Microdevices 10, 795 (2008)CrossRefGoogle Scholar
  6. G. Dai, M.R. Kaazempur-Mofrad, S. Natarajan, Y. Zhang, S. Vaughn, B.R. Glackman, R.D. Kamm, G. Garcia-Cardeña, M.A. Gimbrone, Proc Nat Acad Sci 101, 14871 (2004)CrossRefGoogle Scholar
  7. T.A. Desai, Med Eng Phys 22, 595 (2000)CrossRefGoogle Scholar
  8. D.C. Duffy, J.C. McDonald, O.J.A. Schueller, G.M. Whitesides, Anal Chem 70, 4974 (1998)CrossRefGoogle Scholar
  9. C. Fidkowski, M.R. Kaazempur-Mofrad, J.T. Borenstein, J.P. Vacanti, R. Langer, Y. Wang, Tissue Eng 11, 302 (2005)CrossRefGoogle Scholar
  10. G. García-Cardeña, J. Comander, K.R. Anderson, B.R. Blackman, M.A. Gimbrone Jr., Proc Natl Acad Sci USA 98, 4478 (2001)CrossRefGoogle Scholar
  11. S. Giselbrecht, T. Gietzelt, E. Gottwald, C. Trautmann, R. Truckenmuller, K.F. Weibezahn, A. Welle, Biomed Microdevices 8, 191 (2006)CrossRefGoogle Scholar
  12. J. Green, T. Kniazeva, M. Abedi, D.S. Sokhey, M.E. Taslim, S.K. Murthy, Lab Chip 9, 677 (2009)CrossRefGoogle Scholar
  13. M. Heckele, W.K. Schomburg, J. Micromech. Microeng 14: R1, 7776 (2007)Google Scholar
  14. S. Hu, X. Ren, M. Bachman, C.E. Sims, G.P. Li, N.L. Allbritton, Langmuir 20, 5569 (2004)CrossRefGoogle Scholar
  15. X. Hu, W. Lui, L. Cui, M. Wang, Y. Cao, Tissue Eng 11, 1710 (2005)CrossRefGoogle Scholar
  16. B.-H. Jo, D.J. Beebe, SPIE 3877, 222 (1999)CrossRefGoogle Scholar
  17. M. R. Kaazempur-Mofrad, N. J. Krebs, J. P. Vacanti, J. T. Borenstein, Proceedings of the 2004 Hilton Head Sensors and Actuators Conference (2004)Google Scholar
  18. A. Khademhosseini, R. Langer, J.T. Borenstein, J.P. Vacanti, Proc Nat Acad Sci 103, 2480 (2006)CrossRefGoogle Scholar
  19. K.R. King, C.J. Wang, M.R. Kaazempur-Mofrad, J.P. Vacanti, J.T. Borenstein, Adv Mater 16, 2007 (2004)CrossRefGoogle Scholar
  20. D.A. LaVan, P.M. George, R. Langer, Angew Chem Int Ed 42, 1262 (2003)CrossRefGoogle Scholar
  21. E. Leclerc, Y. Sakai, T. Fujii, Biomed Microdevices 5, 109 (2003)CrossRefGoogle Scholar
  22. D. Lim, Y. Kamotani, B. Cho, J. Mazumder, S. Takayama, Lab Chip 3, 318 (2003)CrossRefGoogle Scholar
  23. R. Lima, S. Wada, S. Tanaka, M. Takeda, T. Ishikawa, K.-I. Tsubota, Y. Imai, T. Yamaguchi, Biomed Microdevices 10, 153 (2008)CrossRefGoogle Scholar
  24. H. Lu, L.Y. Koo, W.M. Wang, D.A. Lauffenburger, L.G. Griffith, K.F. Jensen, Anal Chem 76, 5257 (2004)CrossRefGoogle Scholar
  25. T.C. Marentis, J.P. Vacanti, J. Hsiao, J.T. Borenstein, IEEE JMEMS 2009, in press.Google Scholar
  26. H.L. Prichard, W.M. Reichert, B. Klitzman, Biomaterials 28, 936 (2007)CrossRefGoogle Scholar
  27. S.R. Quake, A. Scherer, Science 290, 1536 (2000)CrossRefGoogle Scholar
  28. G.M. Riha, P.H. Lin, A.B. Lumsden, Q. Yao, C. Chen, Ann Biomed Eng 33, 772 (2005)CrossRefGoogle Scholar
  29. M.K. Runyon, C.J. Kastrup, B.L. Johnson-Kemer, T.G. Ha, R.F. Ismagilov, J Am Chem Soc 130, 3458 (2008)CrossRefGoogle Scholar
  30. C.-T. Seo, C.-H. Bae, D.-S. Eun, J.-K. Shin, J.-H. Lee, Jpn J Appl Phys 43, 7773 (2004)CrossRefGoogle Scholar
  31. F. Shen, C.L. Kastrup, R.R. Ismagilov, Thrombosis Res 122(Suppl. 1), S27 (2008)CrossRefGoogle Scholar
  32. J.W. Song, W. Gu, N. Futai, K.A. Warner, J.E. Nor, S. Takayama, Anal Chem 77, 3993 (2005)CrossRefGoogle Scholar
  33. J.P. Vacanti, R. Langer, The Lancet 354(Suppl I), 32SI (1999)Google Scholar
  34. X.F. Walboomers, H.J. Croes, L.A. Ginsel, J.A. Jansen, Biomaterials 19, 1861 (1998)CrossRefGoogle Scholar
  35. G.-J. Wang, K.-H. Ho, S.-H. Hsu, K.-P. Wang, Biomed Microdevices 9, 657–663 (2007)CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Jeffrey T. Borenstein
    • 1
    • 5
  • Malinda M. Tupper
    • 1
  • Peter J. Mack
    • 3
    • 4
  • Eli J. Weinberg
    • 1
    • 2
  • Ahmad S. Khalil
    • 1
    • 2
  • James Hsiao
    • 1
  • Guillermo García-Cardeña
    • 3
  1. 1.MEMS Technology GroupCharles Stark Draper LaboratoryCambridgeUSA
  2. 2.Department of Mechanical EngineeringMassachusetts Institute of TechnologyCambridgeUSA
  3. 3.Center for Excellence in Vascular Biology, Departments of PathologyBrigham and Women’s Hospital and Harvard Medical SchoolBostonUSA
  4. 4.Harvard-MIT Division of Health Sciences and TechnologyMassachusetts Institute of TechnologyCambridgeUSA
  5. 5.Biomedical Engineering CenterCharles Stark Draper LaboratoryCambridgeUSA

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