Rapid Generation of Biologically Relevant Hydrogels Containing Long-Range Chemical Gradients

Authors

  • Jiankang He,

    1. Center for Biomedical Engineering Department of Medicine Brigham and Women's Hospital Harvard Medical School Boston, MA, 02115 (USA)
    2. Harvard-MIT Division of Health Sciences and Technology Massachusetts Institute of Technology Cambridge, MA, 02139 (USA)
    3. State Key Laboratory of Manufacturing Systems Engineering Xi'an Jiaotong University Xi'an, Shaanxi, 710049 (P. R. China)
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  • Yanan Du,

    1. Center for Biomedical Engineering Department of Medicine Brigham and Women's Hospital Harvard Medical School Boston, MA, 02115 (USA)
    2. Harvard-MIT Division of Health Sciences and Technology Massachusetts Institute of Technology Cambridge, MA, 02139 (USA)
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  • José L. Villa-Uribe,

    1. Center for Biomedical Engineering Department of Medicine Brigham and Women's Hospital Harvard Medical School Boston, MA, 02115 (USA)
    2. Harvard-MIT Division of Health Sciences and Technology Massachusetts Institute of Technology Cambridge, MA, 02139 (USA)
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  • Changmo Hwang,

    1. Center for Biomedical Engineering Department of Medicine Brigham and Women's Hospital Harvard Medical School Boston, MA, 02115 (USA)
    2. Harvard-MIT Division of Health Sciences and Technology Massachusetts Institute of Technology Cambridge, MA, 02139 (USA)
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  • Dichen Li,

    1. State Key Laboratory of Manufacturing Systems Engineering Xi'an Jiaotong University Xi'an, Shaanxi, 710049 (P. R. China)
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  • Ali Khademhosseini

    Corresponding author
    1. Center for Biomedical Engineering Department of Medicine Brigham and Women's Hospital Harvard Medical School Boston, MA, 02115 (USA)
    2. Harvard-MIT Division of Health Sciences and Technology Massachusetts Institute of Technology Cambridge, MA, 02139 (USA)
    • Center for Biomedical Engineering Department of Medicine Brigham and Women's Hospital Harvard Medical School Boston, MA, 02115 (USA).
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Abstract

Many biological processes are regulated by gradients of bioactive chemicals. Thus, the generation of materials with embedded chemical gradients may be beneficial for understanding biological phenomena and generating tissue-mimetic constructs. Here a simple and versatile method to rapidly generate materials containing centimeter-long gradients of chemical properties in a microfluidic channel is described. The formation of a chemical gradient is initiated by a passive-pump-induced forward flow and further developed during an evaporation-induced backward flow. The gradient is spatially controlled by the backward flow time and the hydrogel material containing the gradient is synthesized via photopolymerization. Gradients of a cell-adhesion ligand, Arg-Gly-Asp-Ser (RGDS), are incorporated in poly(ethylene glycol)-diacrylate (PEG-DA) hydrogels to test the response of endothelial cells. The cells attach and spread along the hydrogel material in a manner consistent with the RGDS-gradient profile. A hydrogel containing a PEG-DA concentration gradient and constant RGDS concentration is also shown. The morphology of cells cultured on such hydrogel changes from round in the lower PEG-DA concentration regions to well-spread in the higher PEG-DA concentration regions. This approach is expected to be a valuable tool to investigate the cell–material interactions in a simple and high-throughput manner and to design graded biomimetic materials for tissue engineering applications.

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