Experimental investigation and computational modeling of hydrodynamics in bifurcating microchannels.

Methods involving microfluidics have been used in several chemical, biological and medical applications. In particular, a network of bifurcating microchannels can be used to distribute flow in a large space. In this work, we carried out experiments to determine hydrodynamic characteristics of bifurcating microfluidic networks. We measured pressure drop across bifurcating networks of various complexities for various flow rates. We also measured planar velocity fields in these networks by using particle image velocimetry. We further analyzed hydrodynamics in these networks using mathematical and computational modeling. Our results show that the experimental frictional resistances of complex bifurcating microchannels are 25-30% greater than that predicted by Navier-Stokes equations. Experimentally measured velocity profiles indicate that flow distributes equally at a bifurcation regardless of the complexity of the network. Flow division other than bifurcation such as trifurcation or quadruplication can lead to heterogeneities. These findings were verified by the results from the numerical simulations.

Optimal planar flow network designs for tissue engineered constructs with built-in vasculature.

Convective delivery of nutrients is important to enhance mass transport within tissue engineered (TE) products. Depending on the target tissue, an ideal TE product will have an integrated microvasculature that will eliminate mass transport limitations that can occur during product growth in vitro and integration in vivo. A synthetic approach to develop microvasculature involves development of network designs with efficient mass transfer characteristics. In this paper, utilizing a planar bifurcating network as a basis, we develop an approach to design optimal flow networks that have maximum mass transport efficiency for a given pressure drop. We formulated the optimization problem for a TE skin product, incorporating two types of duct flow, rectangular and square, and solved using a generalized reduced gradient algorithm. Under the conditions of this study, we found that rectangular ducts have superior mass transport characteristics than square ducts. Microvascular area per volume values obtained in this work are significantly greater than those reported in the literature. We discuss the effect of network variables such as porosity and generations on the optimal designs. This research forms the engineering basis for the rational development of TE products with built-in microvasculature and will pave the way to design complex flow networks with optimal mass transfer characteristics.

Lithography Technique for Topographical Micropatterning of Collagen-Glycosaminoglycan Membranes for Tissue Engineering Applications.

BACKGROUND: An adaptable technique for micropatterning biomaterial scaffolds has enormous implications in controlling cell function and in the development of tissue-engineered (TE) microvasculature. In this paper, we report a technique to embed microscale patterns onto a collagen-glycosaminoglycan (CG) membrane as a first step towards the creation of TE constructs with built-in microvasculature. METHOD OF APPROACH: The CG membranes were fabricated by homogenizing a solution of Type I bovine collagen and chondroitin 6-sulfate in acetic acid and vacuum filtering the solution subsequently. The micropatterning technique consisted of three steps: surface dissolution of base matrix using acetic acid solution, feature resolution by application of uniform pressure and feature stability by glutaraldehyde crosslinking. RESULTS: Application of the new technique yielded patterns in CG membranes with a spatial resolution in the order of 2-3 microns. We show that such a patterned matrix is conducive to the attachment of bovine aortic endothelial cells (BAEC's). CONCLUSIONS: The patterned membranes can be used for the development of complex three-dimensional TE products with built-in flow channels, as templates for topographically directed cell growth, or as a model system to study various microvascular disorders where feature scales are important. The new technique is versatile; topographical patterns can be custom-made for any predetermined design with high spatial resolution and the technique itself can be adapted for use with other scaffold materials.