Journal
BIOMATERIALS
Volume 28, Issue 33, Pages 4939-4946Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2007.08.002
Keywords
thermally responsive material; endothelial cell; co-culture; micropatterning; 3-d fabrication; tissue engineering
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Tissue engineering seeks to provide regenerated tissue architectures in vitro but has not yet successfully created thick, highly vascularized, multi-functional tissues replicating native structure. We describe a novel method to fabricate pre-vascularized tissue equivalents using multi-layered cultures combining micro-patterned endothelial cells as vascular pre-cursors with fibroblast monolayer sheets as tissue matrix. Stratified tissue equivalents are constructed by alternately layering fibroblast monolayer sheets with patterned endothelial cell sheets harvested from newly developed thermo-responsive micro-patterned surfaces alternating 20 pm-wide cell-adhesive lanes with 60 pin non-adhesive zones. Cell culture substrates covalently grafted with different thermo-responsive polymers permit spatial switching of cell adhesion and detachment using applied small temperature changes. Endothelial cell patterning fidelity was maintained within the multi-layer tissue constructs after assembly, leading to self-organization into microvascular-like networks after 5-day tissue Culture. This novel technique holds promise for the study of cell-cell communications and angiogenesis in reconstructed, three-dimensional environments as well as for the fabrication of tissues with complex, multicellular architecture. (c) 2007 Elsevier Ltd. All rights reserved.
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