Skip to main content
Log in

Microfluidic vascular-bed devices for vascularized 3D tissue engineering: tissue engineering on a chip

  • Published:
Biomedical Microdevices Aims and scope Submit manuscript

Abstract

In this report, we describe a microfluidic vascular-bed (micro-VB) device providing a platform for 3D tissue engineering with vascular network formation. The micro-VB device allows functional connections between endothelial capillaries of heterogeneous sections (5–100 μm in diameter) and artificial plastic tubes or reservoirs (1–10 mm in diameter). Moreover, the micro-VB device can be installed in a standard 100 mm-diameter Petri dish. Endothelial networks in 3D engineered tissues were obtained by cellular self-assembly on the device, after co-culturing of human umbilical vein endothelial cells (HUVECs) and normal human dermal fibroblasts (NHDFs) in fibrin gel. Endothelial capillary connection between vascularized tissues and microfluidic channels, mimicking arteries and veins, was confirmed by perfusion of fluorescent microspheres. The micro-VB devices were compatible with the use of commercially available culture dishes and did not require the involvement of additional equipment. Thus, these micro-VB devices are expected to substantially improve the routine application of 3D tissue engineering to regenerative medicine.

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

  • A. Armulik, A. Abramsson, C. Betsholtz, Endothelial/pericyte interactions. Circ. Res. 97(6), 512–523 (2005)

    Article  Google Scholar 

  • F.S. Frueh, M.D. Menger, N. Lindenblatt, P. Giovanoli, M.W. Laschke, Current and emerging vascularization strategies in skin tissue engineering. Crit. Rev. Biotechnol. 37(5), 613–625 (2017)

    Article  Google Scholar 

  • M.E. Gomes, M.T. Rodrigues, R.M. Domingues, R.L. Reis, Tissue engineering and regenerative medicine: New trends and directions—A year in review. Tissue Eng. B Rev. 23(3), 211–224 (2017)

    Article  Google Scholar 

  • B. Harink, S. Le Gac, R. Truckenmüller, C.A. van Blitterswijk, P. Habibovic, Regeneration-on-a-Chip? The perspectives on use of microfluidics in regenerative medicine. Lab Chip 13, 3512–3528 (2013)

    Article  Google Scholar 

  • K. Itoga, J. Kobayashi, Y. Tsuda, M. Yamato, T. Okano, Second-generation maskless photolithography device for surface micropatterning and microfluidic channel fabrication. Anal. Chem. 80(4), 1323–1327 (2008)

    Article  Google Scholar 

  • R.K. Jain, P. Au, J. Tam, D.G. Duda, D. Fukumura, Engineering vascularized tissue. Nat. Biotechnol. 23(7), 821–823 (2005)

    Article  Google Scholar 

  • S. Kim, H. Lee, M. Chung, N.L. Jeon, Engineering of functional, perfusable 3D microvascular networks on a chip. Lab Chip 13, 1489–1500 (2013)

    Article  Google Scholar 

  • N. Koike, D. Fukumura, O. Gralla, P. Au, J.S. Schechner, R.K. Jain, Tissue engineering: Creation of long-lasting blood vessels. Nature. 428(6979), 138–139 (2004)

    Article  Google Scholar 

  • M. Kojima, H. Takehara, T. Akagi, H. Shiono, T. Ichiki, Flexible sheet-type sensor for noninvasive measurement of cellular oxygen metabolism on a culture dish. PLoS One 10(12), e0143774 (2015)

    Article  Google Scholar 

  • J.S. Miller, K.R. Stevens, M.T. Yang, B.M. Baker, D.-H.T. Nguyen, D.M. Cohen, E. Toro, A.A. Chen, P.A. Galie, X. Yu, Rapid casting of patterned vascular networks for perfusable engineered three-dimensional tissues. Nat. Mater. 11, 768–774 (2012)

    Article  Google Scholar 

  • K.T. Morin, R.T. Tranquillo, In vitro models of angiogenesis and vasculogenesis in fibrin gel. Exp. Cell Res. 319(16), 2409–2417 (2013)

    Article  Google Scholar 

  • M.L. Moya, Y.-H. Hsu, A.P. Lee, C.C. Hughes, S.C. George, In vitro perfused human capillary networks. Tissue Engineering Part C: Methods. 19(9), 730–737 (2013)

    Article  Google Scholar 

  • E.C. Novosel, C. Kleinhans, P.J. Kluger, Vascularization is the key challenge in tissue engineering. Adv. Drug Deliv. Rev. 63(4), 300–311 (2011)

    Article  Google Scholar 

  • J. Rouwkema, N.C. Rivron, C.A. van Blitterswijk, Vascularization in tissue engineering. Trends Biotechnol. 26(8), 434–441 (2008)

    Article  Google Scholar 

  • K. Sakaguchi, T. Shimizu, S. Horaguchi, H. Sekine, M. Yamato, M. Umezu, T. Okano, In vitro engineering of vascularized tissue surrogates. Sci. Rep. 3, 1316 (2013)

    Article  Google Scholar 

  • H. Sekine, T. Shimizu, K. Sakaguchi, I. Dobashi, M. Wada, M. Yamato, E. Kobayashi, M. Umezu, T. Okano, In vitro fabrication of functional three-dimensional tissues with perfusable blood vessels. Nat. Commun. 4, 1399 (2013)

    Article  Google Scholar 

  • S. Sekiya, T. Shimizu, T. Okano, Vascularization in 3D tissue using cell sheet technology. Regen. Med. 8(3), 371–377 (2013)

    Article  Google Scholar 

  • J.J. Song, J.P. Guyette, S.E. Gilpin, G. Gonzalez, J.P. Vacanti, H.C. Ott, Regeneration and experimental orthotopic transplantation of a bioengineered kidney. Nat. Med. 19(5), 646–651 (2013)

    Article  Google Scholar 

  • H.-H.G. Song, R.T. Rumma, C.K. Ozaki, E.R. Edelman, C.S. Chen, Vascular tissue engineering: Progress, challenges, and clinical promise. Cell Stem Cell 22(3), 340–354 (2018)

    Article  Google Scholar 

  • H. Takehara, K. Sakaguchi, M. Kuroda, M. Muraoka, K. Itoga, T. Okano, T. Shimizu, Controlling shape and position of vascular formation in engineered tissues by arbitrary assembly of endothelial cells. Biofabrication 7(4), 045006 (2015)

    Article  Google Scholar 

  • B.E. Uygun, A. Soto-Gutierrez, H. Yagi, M.-L. Izamis, M.A. Guzzardi, C. Shulman, J. Milwid, N. Kobayashi, A. Tilles, F. Berthiaume, Organ reengineering through development of a transplantable recellularized liver graft using decellularized liver matrix. Nat. Med. 16(7), 814–820 (2010)

    Article  Google Scholar 

  • P.-J. Wipff, H. Majd, C. Acharya, L. Buscemi, J.-J. Meister, B. Hinz, The covalent attachment of adhesion molecules to silicone membranes for cell stretching applications. Biomaterials. 30(9), 1781–1789 (2009)

    Article  Google Scholar 

  • Y. Xia, G.M. Whitesides, Soft lithography. Annu. Rev. Mater. Sci. 28(1), 153–184 (1998)

    Article  Google Scholar 

  • B. Zhang, M. Montgomery, M.D. Chamberlain, S. Ogawa, A. Korolj, A. Pahnke, L.A. Wells, S. Massé, J. Kim, L. Reis, Biodegradable scaffold with built-in vasculature for organ-on-a-chip engineering and direct surgical anastomosis. Nature materials 15(6), 669 (2016)

    Article  Google Scholar 

  • Y. Zheng, P.W. Henderson, N.W. Choi, L.J. Bonassar, J.A. Spector, A.D. Stroock, Microstructured templates for directed growth and vascularization of soft tissue in vivo. Biomaterials. 32(23), 5391–5401 (2011)

    Article  Google Scholar 

  • Y. Zheng, J. Chen, M. Craven, N.W. Choi, S. Totorica, A. Diaz-Santana, P. Kermani, B. Hempstead, C. Fischbach-Teschl, J.A. López, In vitro microvessels for the study of angiogenesis and thrombosis. Proc. Natl. Acad. Sci. 109(24), 9342–9347 (2012)

    Article  Google Scholar 

  • E. Zudaire, L. Gambardella, C. Kurcz, S. Vermeren, A computational tool for quantitative analysis of vascular networks. PLoS One 6(11), e27385 (2011)

    Article  Google Scholar 

Download references

Acknowledgments

This research was supported by funding from the Japan Society for the Promotion of Science (JSPS) through the Funding Program for World-Leading Innovative R&D on Science and Technology (FIRST Program), initiated by the Council for Science and Technology Policy (CSTP).

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Hiroaki Takehara or Tatsuya Shimizu.

Ethics declarations

Ethics and dissemination

Research ethics approval is not required for this study.

Competing financial interests

The authors declare no competing financial interests.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Takehara, H., Sakaguchi, K., Sekine, H. et al. Microfluidic vascular-bed devices for vascularized 3D tissue engineering: tissue engineering on a chip. Biomed Microdevices 22, 9 (2020). https://doi.org/10.1007/s10544-019-0461-2

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s10544-019-0461-2

Keywords

Navigation