Microscale multilayer cocultures for biomimetic blood vessels.
Living tissues have complex and well-organized microstructures. Although microtechnology has been used to create in vivo-like cell microstructures in vitro, most available microscale systems are two-dimensional, and few three-dimensional (3D) systems have been explored. This article demonstrates a 3D hierarchical biomimetic multilayer microsystem created by a generally applicable technique. The technique employs layer-by-layer microfluidics to build layers of cells and biopolymers in microchannels, allowing controlled patterning of cells and their microenvironments in the x, y, and z-dimension. As a prototype, a multilayer system was created using three vascular cell types within heterogeneous types of biopolymers to mimic the structure and composition of a blood vessel wall. The effects of matrix composition and multilayer configurations on 3D cell-cell interactions and cell biology were revealed. Cell migration in the z-dimension, matrix remodeling, intercellular adhesion molecule expression and actin organization were examined under different 3D coculture conditions. A more biomimetic coculture was found to reproduce a more stable structure and in vivo-like function. This approach provides a method to fabricate microscale hierarchical "neotissues" with 3D configurations of matrix materials and multiple cell types, and an in vitro cell coculture model to understand 3D processes of cell-cell and cell-matrix interactions.
Tan
Wei
W
Beckman Institute, University of Illinois at Urbana-Champaign, 405 North Mathews Avenue, Urbana, Illinois, USA.
Desai
Tejal A
TA
D008841:Actin Cytoskeleton / Q000378:metabolism; D040761:Biomimetic Materials / Q000737:chemistry*; D001808:Blood Vessels; D002448:Cell Adhesion; D002465:Cell Movement; D002478:Cells, Cultured; D018920:Coculture Techniques; D003094:Collagen / Q000494:pharmacology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D044085:Microfluidics; D018613:Microscopy, Confocal; D008855:Microscopy, Electron, Scanning; D023822:Tissue Engineering / Q000379:methods*
D018799:Intercellular Adhesion Molecule-1; D003094:Collagen