Research ArticleAPPLIED PHYSICS

Constructing 3D heterogeneous hydrogels from electrically manipulated prepolymer droplets and crosslinked microgels

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Science Advances  26 Oct 2016:
Vol. 2, no. 10, e1600964
DOI: 10.1126/sciadv.1600964
  • Fig. 1 Programmable electromicrofluidic platform for microgel formation and architecture assembly.

    (A) Top and cross-sectional views of a conceptual electromicrofluidic platform that assembles an architecture consisting of 3 × 3 microgels prepared from four crosslinkable elementary materials (W, R, G, and B) through manipulations of suspended particles, liquid droplets, and crosslinked microgels by electrowetting and dielectrophoresis between parallel plates with appropriate electrodes and dielectric and hydrophobic layers. (B) Change of contact angle by electrowetting on sessile drops of water, PEGDA, and their mixtures with varied concentrations. DI, deionized; deg, degrees. (C) Moving velocity of a PEGDA droplet driven by dielectrophoresis on the electromicrofluidic platform. (D to H) Producing microgels by aliquoting, merging, mixing, splitting, and transporting, PEGDA droplets with rhodamine 6G (R6G) (R), fluorescein (G), and coumarin 450 (C-450) (B) dyes. (I) Crosslinking of single (G) and Janus binary (B/B+G and G+R/R) microgels after light exposure. (J) Microgels with configurable encoding colors by droplet manipulations (movie S1). (K) Hexagonal microgel. Scale bars, 1 mm.

  • Fig. 2 Multiphase post- and precrosslinking assemblies of architecture on the electromicrofluidic platform.

    (A to C) Postcrosslinking assembly of crosslinked PEGDA microgels driven in water (movie S2). (D and E) Precrosslinking assembly of nine PEGDA prepolymer droplets with varied dyes to form a heterogeneous architecture (3 mm × 3 mm × 100 μm) after crosslinking on light exposure (movie S3). (F) Fluorescence microscopy image of the crosslinked heterogeneous architecture. (G) Architecture accessible with tweezers. Scale bars, 1 mm.

  • Fig. 3 Multiphase and cross-scale assembly of architectures with microgels consisting of varied prepolymer solutions, dyes, and particles.

    (A) Microgels crosslinked by different manners on a single electromicrofluidic platform. Left: PEGDA with green particles by photocrosslinking; middle: Matrigel with blue dye by thermal crosslinking; right: polyacrylamide with red particles by chemical crosslinking. (B to G) Postcrosslinking PEGDA microgels, containing random or reorganized encoding particles, assembled (B to D) and stacked (E to G) in liquid PEGDA solution (movie S4). (H and I) Precrosslinking assembly of nine PEGDA droplets with dye or addressable particles to form a PEGDA architecture (3 mm × 3 mm × 100 μm) after crosslinking on light exposure (movie S5). (J and K) Fluorescence microscopy images of the crosslinked and seamless heterogeneous architecture. Scale bars, 1 mm (A to J); 200 μm (K).

  • Fig. 4 2D and 3D cell culture on architectures and within microgels with cross-scale cell patterns configured by surface properties and inner electric fields.

    (A and B) NIH/3T3 fibroblasts, stained with Alexa Fluor 488 phalloidin (F-actin, green) and DAPI (nuclei, blue) at 48 hours in culture, growing on GelMA (8%) but not on PEGDA of the heterogeneous architecture. (C and D) Neonatal mouse cardiomyocytes patterned with GelMA/PEGDA surfaces and stained with Alexa Fluor 488 phalloidin, DAPI, and Cy3 (cTnI) at 48 hours in culture. (E) Cardiomyocyte ratio over the entire cells at 48 hours in culture on a 24-well plate as control and on GelMA of the architecture. (F) Beating rate of the cardiomyocytes at 24 and 48 hours in culture on GelMA of the architecture (movie S6). (G) GelMA (5%) microgel crosslinked with encapsulated random NIH/3T3 fibroblasts. (H) GelMA/cell microgel in (G) stained with Alexa Fluor 488 phalloidin and DAPI on day 5 in culture. (I) GelMA microgel crosslinked with encapsulated and reorganized NIH/3T3 fibroblasts (movie S7). (J) GelMA/cell microgels in (I) stained on day 3 in culture. *P < 0.01. Scale bars, 200 μm.

Supplementary Materials

  • Supplementary material for this article is available at http://advances.sciencemag.org/cgi/content/full/2/10/e1600964/DC1

    Electrowetting (EWOD)

    Dielectrophoresis on liquids (LDEP)

    Dielectrophoresis on particles (DEP)

    Dielectrophoresis on crosslinked microgels (SDEP)

    fig. S1. Configuration and manipulations on an electromicrofluidic platform.

    fig. S2. Visualization of a heterogeneous architecture with a fluorescence microscope, a fluorescence confocal microscope, and an SEM.

    fig. S3. NIH/3T3 fibroblast culture on heterogeneous architecture composed of PEGDA and GelMA.

    movie S1. Manipulation and crosslinking of liquid microgels (Fig. 1J).

    movie S2. Postcrosslinking assembly of microgels (Fig. 2, A to C).

    movie S3. Precrosslinking assembly of microgels (Fig. 2, D and E).

    movie S4. Postcrosslinking assembly of microgels with particles (Fig. 3, B to G).

    movie S5. Precrosslinking assembly of microgels with particles (Fig. 3, H and I).

    movie S6. Beating of patterned cardiomyocytes at 24 and 48 hours in culture (Fig. 4F).

    movie S7. Manipulation and crosslinking of microgels with cells (Fig. 4I).

  • Supplementary Materials

    This PDF file includes:

    • Electrowetting (EWOD)
    • Dielectrophoresis on liquids (LDEP)
    • Dielectrophoresis on particles (DEP)
    • Dielectrophoresis on crosslinked microgels (SDEP)
    • fig. S1. Configuration and manipulations on an electromicrofluidic platform.
    • fig. S2. Visualization of a heterogeneous architecture with a fluorescence microscope, a fluorescence confocal microscope, and an SEM.
    • fig. S3. NIH/3T3 fibroblast culture on heterogeneous architecture composed of PEGDA and GelMA.
    • Legends for movies S1 to S7

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    Other Supplementary Material for this manuscript includes the following:

    • movie S1 (.mpg format). Manipulation and crosslinking of liquid microgels (Fig. 1J).
    • movie S2 (.mpg format). Postcrosslinking assembly of microgels (Fig. 2, A to C).
    • movie S3 (.mpg format). Precrosslinking assembly of microgels (Fig. 2, D and E).
    • movie S4 (.mpg format). Postcrosslinking assembly of microgels with particles (Fig. 3, B to G).
    • movie S5 (.mpg format). Precrosslinking assembly of microgels with particles (Fig. 3, H and I).
    • movie S6 (.mpg format). Beating of patterned cardiomyocytes at 24 and 48 hours in culture (Fig. 4F).
    • movie S7 (.mpg format). Manipulation and crosslinking of microgels with cells (Fig. 4I).

    Files in this Data Supplement:

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