Hostname: page-component-586b7cd67f-dsjbd Total loading time: 0 Render date: 2024-11-28T07:10:23.461Z Has data issue: false hasContentIssue false

Design and Fabrication of a Constant Shear Microfluidic Network for Tissue Engineering

Published online by Cambridge University Press:  17 March 2011

E.J. Weinberg
Affiliation:
The Charles Stark Draper Laboratory, 555 Technology Square, Cambridge MA Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge MA
J.T. Borenstein
Affiliation:
The Charles Stark Draper Laboratory, 555 Technology Square, Cambridge MA
M.R. Kaazempur-Mofrad
Affiliation:
Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge MA
B. Orrick
Affiliation:
The Charles Stark Draper Laboratory, 555 Technology Square, Cambridge MA
J.P. Vacanti
Affiliation:
Massachusetts General Hospital, 32 Fruit Street, Boston MA Harvard Medical School, Boston MA
Get access

Abstract

Recent progress in microfabrication of biodegradable materials has resulted in the development of a three-dimensional construct suitable for use as a scaffold for engineering blood vessel networks. These networks are designed to replicate the critical fluid dynamic properties of physiological systems such as the microcirculation within a vital organ. Ultimately, these 3D microvascular constructs will serve as a framework for population with organ-specific cells for applications in organ assist and organ replacement. This approach for tissue engineering utilizes highly engineered designs and microfabrication technology to assemble cells in three-dimensional constructs which have physiological values for properties such as mechanical strength, oxygen, nutrient and waste transport, and fluidic parameters such as flow volume and pressure.

Three-dimensional networks with appropriate values for blood flow velocity, pressure drop and hematocrit distribution have been designed and fabricated using replica molding techniques, and populated with endothelial cells for long-term microfluidic cell culture. One critical aspect of the fluid dynamics of these systems is the shear stress exerted by blood flow at the walls of the vessel; a key parameter because of well-known mechanotransduction phenomena from mechanical shear forces which govern endothelial cell behavior. In this work, we report the design and construction of three-dimensional microfluidic constructs for tissue engineering which have uniform wall shear stress throughout the network. This type of control over the shear stress offers several advantages over earlier approaches, including more uniform seeding, more rapid achievement of confluent coatings, and better control over endothelial cell behavior for in vitro and in vivo studies.

Type
Research Article
Copyright
Copyright © Materials Research Society 2004

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1. Vacanti, J.P. and Langer, R., “Tissue Engineering: Design and Fabrication of Living Replacement Devices for Surgical Reconstruction and Transplantation,” Lancet 354 (Suppl. I) 32 (1999).Google Scholar
2. Niklason, L.E. and Langer, R., “Prospects for Organ and Tissue Replacement,” JAMA 285 573 (2001).CrossRefGoogle ScholarPubMed
3. Borenstein, J.T., Terai, H., King, K.R., Weinberg, E.J., Kaazempur-Mofrad, M.R. and Vacanti, J.P., “Microfabrication Technology for Vascularized Tissue Engineering”, Biomedical Microdevices 4 167–75 (2002).CrossRefGoogle Scholar
4. Borenstein, J.T., Cheung, W., Hartman, L., Kaazempur-Mofrad, M.R., King, K.R., Sevy, A., Shin, M., Weinberg, E.J. and Vacanti, J.P., “Living Three-Dimensional Microfabricated Constructs for the Replacement Of Vital Organ Function,” Proc. 12th Int'l. Conf. Solid State Sensors, Actuators and Microsystems (Transducers 2003), 1754–7 (2003).Google Scholar
5. Malek, A., Alper, S.I. and Izumo, S., “Hemodynamic Shear Stress and its Role in Atherosclerosis,” JAMA 282 2035 (1999).Google Scholar
6. Weinberg, EJ. Design of two-dimensional microvasculature for tissue engineering (BS thesis). MIT, 2001.Google Scholar
7. Thorpe, TW. Computerized circuit analysis with SPICE: a complete guide to SPICE, with applications. New York: Kluwer Academic, 1992.Google Scholar
8. Weinberg, EJ, Kaazempur-Mofrad, MR, Borenstein, JT. “Numerical Model of Flow in Distensible Microfluidic Network”, Computational Fluid and Solid Mechanics 2003 (Ed. Bathe, KJ), Vol. 2: 15691572, Oxford: Elsevier Science Ltd, 2003.CrossRefGoogle Scholar
9. Weinberg, EJ, Kaazempur-Mofrad, MR, “Shear-Based Generation of Physiological Vasculature”, to be published.Google Scholar
10. Davies, PF. “Mechanisms involved in endothelial responses to hemodynamic forces”, Atherosclerosis, 131: S15–S17 Suppl.S, 1997.Google Scholar