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A multilayered microfluidic blood vessel-like structure

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Abstract

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.

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Acknowledgments

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.

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Authors and Affiliations

  1. Biomedical Engineering, and Department of Mechanical Engineering, Faculty of Engineering and Architecture, American University of Beirut, Beirut, 1107 2020, Lebanon

    Anwarul Hasan

  2. Biomaterials Innovation Research Center, Division of Biomedical Engineering, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Cambridge, MA, 02139, USA

    Anwarul Hasan, Arghya Paul & Ali Khademhosseini

  3. Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA

    Anwarul Hasan, Arghya Paul & Ali Khademhosseini

  4. Department of Chemical and Petroleum Engineering, University of Kansas, Lawrence, KS, 66045-7609, USA

    Arghya Paul

  5. Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, 02115, USA

    Arghya Paul & Ali Khademhosseini

  6. Center of Nanotechnology, King Abdulaziz University, Jeddah, 21589, Saudi Arabia

    Adnan Memic

  7. World Premier International – Advanced Institute for Materials Research (WPI-AIMR), Tohoku University, Sendai, 980-8577, Japan

    Ali Khademhosseini

  8. Department of Physics, King Abdulaziz University, Jeddah, 21589, Saudi Arabia

    Ali Khademhosseini

Authors
  1. Anwarul Hasan
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  2. Arghya Paul
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  4. Ali Khademhosseini
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Corresponding authors

Correspondence to Anwarul Hasan or Ali Khademhosseini.

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FIG. S1

Optimization of GelMA concentration for fabrication of blood vessel-like structures: phase contrast images showing smoothness of the tube surface at different concentrations of GelMA. At (a) 4 % and (b) 8 % concentrations, the surface of the lumen got ruptured during the retrieval of the needle after gel formation. At (c) 12 % and higher concentrations the gels were strong enough to retain their structures and resulted in smooth channels. i.e., stiffer GlelMA resulted in smoother channel compared to low concentration GelMA. Scale bar = 200 μm. (DOCX 110 kb)

FIG. S2

Optimization of mechanical properties of fabricated blood vessel-like structures was performed using uniaxial compressive mechanical test on fabricated cell laden monolayer blood vessel-like structures, (a) schematic and dimension of the constructs for mechanical test, (b) stress–strain graph, (c) compressive modulus, (d) failure stress and (e) failure strain for vessels of different GelMA concentrations. The compressive modulus and failure stress of the constructs increased while the failure strain decreased with increase in GelMA concentration. (DOCX 144 kb)

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Hasan, A., Paul, A., Memic, A. et al. A multilayered microfluidic blood vessel-like structure. Biomed Microdevices 17, 88 (2015). https://doi.org/10.1007/s10544-015-9993-2

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