title: Layer-by-layer microfluidics for biomimetic three-dimensional structures.
abstract: Due to the complex structures of living systems, with size scales spanning from the micron to millimeter range, the use of microtechnology to recreate in vivo-like architecture has exciting potential applications. However, most microscale systems are two-dimensional, and few three-dimensional (3-D) systems are being explored. We have developed a versatile technique, combining surface engineering with layer-by-layer microfluidics technology, to create a 3-D microscale hierarchical tissue-like structure. The process involves immobilization of a cell-matrix assembly, cell-matrix contraction, and pressure-driven microfluidic delivery. An aminopropyltriethoxysilane-glutaraldehyde activated chip is used to effectively immobilize the cell-matrix assemblies while maintaining cell viability. Pressure-driven microfluidics is applied to transport cells-matrices with controlled flow rates, determined from dynamic flow imaging. By taking advantage of the contraction of the biopolymer matrices by cells, layer-by-layer microfluidics can be used to build multilayers of cell-matrix inside a microchannel and the thickness of each layer can be controlled down to microscale dimensions. Confocal and electron microscopy images of the final structure show a hierarchical layered cellular configuration composed of heterogeneous biomimetic materials. For a model system, a biomimetic arterial structure is formed using three types of vascular cells to mimic the 3-tunic structure found in vivo. This approach provides solutions to fabricate hierarchical "neotissues" with controlled microarchitectures and 3-D configurations of multiple cell types.
authors.affiliation: Department of Biomedical Engineering, Boston University, 44 Cummington Street, Boston, MA 02215, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Tan
authors.forename: Tejal A
authors.initials: TA
authors.lastname: Desai
mesh_terms: D040761:Biomimetic Materials / Q000138:chemical synthesis* / Q000737:chemistry; D018929:Cell Culture Techniques; D002460:Cell Line; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D020099:Coated Materials, Biocompatible / Q000138:chemical synthesis* / Q000737:chemistry; D042783:Endothelial Cells / Q000166:cytology / Q000502:physiology*; D005109:Extracellular Matrix / Q000737:chemistry / Q000502:physiology* / Q000648:ultrastructure; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology*; D006801:Humans; D008422:Materials Testing; D044085:Microfluidics / Q000379:methods*; D023822:Tissue Engineering / Q000379:methods*
chemical_list: D020099:Coated Materials, Biocompatible