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Microfluidic scaffolds for tissue engineering

Abstract

Most methods to culture cells in three dimensions depend on a cell-seedable biomaterial to define the global structure of the culture and the microenvironment of the cells. Efforts to tailor these scaffolds have focused on the chemical and mechanical properties of the biomaterial itself. Here, we present a strategy to control the distributions of soluble chemicals within the scaffold with convective mass transfer via microfluidic networks embedded directly within the cell-seeded biomaterial. Our presentation of this strategy includes: a lithographic technique to build functional microfluidic structures within a calcium alginate hydrogel seeded with cells; characterization of this process with respect to microstructural fidelity and cell viability; characterization of convective and diffusive mass transfer of small and large solutes within this microfluidic scaffold; and demonstration of temporal and spatial control of the distribution of non-reactive solutes and reactive solutes (that is, metabolites) within the bulk of the scaffold. This approach to control the chemical environment on a micrometre scale within a macroscopic scaffold could aid in engineering complex tissues.

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Figure 1: Schematic representations of cellular microfluidic scaffolds.
Figure 2: Fabrication of cellular microfluidic scaffolds.
Figure 3: Transport characteristics and operation of a microfluidic scaffold.
Figure 4: Delivery of metabolites via a microfluidic network.
Figure 5: Spatially resolved delivery of solutes via embedded microfluidic networks.

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Acknowledgements

We acknowledge the technical assistance of G. Swan, P. Gordnier, S. Degala and P. Miller. We thank M. Shuler for use of cell lines. We acknowledge the financial support of the Office of Naval Research Young Investigator Program, the Arnold and Mabel Beckman Foundation Young Investigator Award, an Innovation Grant from the New York State Office of Science, Technology, and Academic Research, the Cornell Nanobiotechnology Center (NSF-STC, No. ECS-9876771), the Cornell Center for Nanoscale Science (Grant ECS 03-35765) and the Cornell Center for Materials Research (NSF-MRSEC, Grant DMR-0079992).

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Contributions

A.D.S., L.J.B. and M.C. conceived the project. A.D.S. and L.J.B. directed the research. N.W.C. carried out the bulk of the experiments and analyses. M.C., B.H. and J.P.G. aided in the experimental design and carried out specific experiments. A.D.S. and N.W.C. wrote the manuscript. All authors edited the manuscript.

Corresponding authors

Correspondence to Lawrence J. Bonassar or Abraham D. Stroock.

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Supplementary Information

Supplementary information, methods and figures S1-S9 (PDF 1748 kb)

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Choi, N., Cabodi, M., Held, B. et al. Microfluidic scaffolds for tissue engineering. Nature Mater 6, 908–915 (2007). https://doi.org/10.1038/nmat2022

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