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

Abstract

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.