A multilayered microfluidic blood vessel-like structure
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There is an immense need for tissue engineered blood vessels. However, current tissue engineering approaches still lack the ability to build native blood vessel-like perfusable structures with multi-layered vascular walls. This paper demonstrated a new method to fabricate tri-layer biomimetic blood vessel-like structures on a microfluidic platform using photocrosslinkable gelatin hydrogel. The presented method enables fabrication of physiological blood vessel-like structures with mono-, bi- or tri-layer vascular walls. The diameter of the vessels, the total thickness of the vessel wall and the thickness of each individual layer of the wall were independently controlled. The developed fabrication process is a simple and rapid method, allowing the physical fabrication of the vascular structure in minutes, and the formation of a vascular endothelial cell layer inside the vessels in 3–5 days. The fabricated vascular constructs can potentially be used in numerous applications including drug screening, development of in vitro models for cardiovascular diseases and/or cancer metastasis, and study of vascular biology and mechanobiology.
KeywordsTissue engineering Microfluidics Blood vessel Hydrogel PDMS Microfabrication
Anwarul Hasan acknowledges the startup grant and the URB (University Research Board) grant from American University of Beirut, Lebanon, and the CNRS (National Council for Scientific Research) grant, Lebanon. Ali Khademhosseini acknowledges funding from the National Science Foundation (EFRI-1240443), IMMODGEL (602694), and the National Institutes of Health (EB012597, AR057837, DE021468, HL099073, AI105024, AR063745). The authors acknowledge the assistance from Gi Seok Jeong in drawing/editing a part of Fig. 1, and scientific/technical discussions with Joe Tien from Boston University. Arghya Paul likes to acknowledge the Institutional Development Award (IDeA) from the National Institute of General Medical Sciences, National Institutes of Health (NIH), under Award Number P20GM103638-04. Adnan Memic and Ali Khademhosseini would like to thank the National Plan for Science, Technology and Innovation (MAARIFAH) by King Abdulaziz City for Science and Technology, Grant No. 12-MED3096-3 for their support and funding of this project.
- J. Barthes, H. Özçelik, M. Hindié, A. Ndreu-Halili, A. Hasan, N.E. Vrana, Cell microenvironment engineering and monitoring for tissue engineering and regenerative medicine: the recent advances. BioMed research international 2014, p. 18. doi: 10.1155/2014/921905
- Y. Du, D. Cropek, M.R.K. Mofrad, E.J. Weinberg, A. Khademhosseinil, J. Borenstein, in Microfluidics for biological applications, ed. by W.-C. Tian, E. Finehout (Springer, New York, 2008)Google Scholar
- A. Hasan, M. Nurunnabi, M. Morshed, A. Paul, A. Polini, T. Kuila, M. Al Hariri, Y-k. Lee, A.A. Jaffa, Recent advances in application of biosensors in tissue engineering. BioMed research international 2014, p. 18 (2014d)Google Scholar
- A. Hasan, A. Khattab, M.A. Islam, K.A. Hweij, J. Zeitouny, R. Waters, M. Sayegh, M. Hossain, A. Paul, Injectable hydrogels for cardiac tissue repair after myocardial infarction. Adv. Sci. (2015). doi: 10.1002/advs.201500122
- 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, R. Chaturvedi, S.N. Bhatia, C.S. Chen, Rapid casting of patterned vascular networks for perfusable engineered three-dimensional tissues. Nat. Mater. 11, 768–74 (2012)CrossRefGoogle Scholar
- M.N. Nakatsu, R.C.A. Sainson, J.N. Aoto, K.L. Taylor, M. Aitkenhead, S. Pérez-del-Pulgar, P.M. Carpenter, C.C.W. Hughes, Angiogenic sprouting and capillary lumen formation modeled by human umbilical vein endothelial cells (HUVEC) in fibrin gels: the role of fibroblasts and Angiopoietin-1. Microvasc. Res. 66, 102–12 (2003)CrossRefGoogle Scholar