Design and Fabrication of a Constant Shear Microfluidic Network for Tissue Engineering
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Design and Fabrication of a Constant Shear Microfluidic Network for Tissue Engineering E.J. Weinberg1,2, J.T. Borenstein1, M.R. Kaazempur-Mofrad2, B. Orrick1 and J.P. Vacanti3,4 1
The Charles Stark Draper Laboratory, 555 Technology Square, Cambridge MA Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge MA 3 Massachusetts General Hospital, 32 Fruit Street, Boston MA 4 Harvard Medical School, Boston MA 2
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 threedimensional 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. INTRODUCTION The field of regenerative medicine is progressing rapidly, spurred by advances in cell and molecular biology, biomaterials, microfabrication and transplant medicine1,2. A critical component in the tissue engineering of vital organs is the requirement for a vascular supply. Distribution of oxygen and nutrients throughout engineered tissues represents a stringent requirement, driven by the short diffusion lengths of these species through tissue. An approach being pursued by this research team is the use of computational fluid dynamics and microfabrication technology to design and build an in vitro vascular network for engineered tissues and organs3,4. This approach invokes the use of mathematical models to generate engineered vascular networks with physiologic properties, combined
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