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    Biomaterials

    Tuning Stiffness of 3D-Printed Anisotropic Hydrogel Lattices to Mimic White Matter in the Brain

    (C-100) Tuning Stiffness of 3D-Printed Anisotropic Hydrogel Lattices to Mimic White Matter in the Brain

    Friday, October 13, 2023
    9:30 AM – 10:30 AM PDT
    Location: Exhibit Hall - Row C - Poster # 100

      Presenting Author(s)

    • Aaliyah Thompson-Mazzeo (she/her/hers)

      Undergraduate Researcher
      University of Arizona
      Tucson, Arizona, United States

      • Co-Author(s)

    • KE

      Kevin Eckstein

      Postdoctoral Researcher
      Washington University in St. Louis, United States

    • DY

      Daniel Yoon

      Graduate Research Assistant
      Washington University in St. Louis, United States

    • MR

      Margrethe Ruding

      Graduate Research Assistant
      Washington University in St. Louis, United States

      • Primary Investigator(s)

    • PB

      Philip Bayly, n/a

      Professor
      Washington University in St. Louis, United States

    Introduction::

    Traumatic Brain Injury is the leading cause of death and disability in people aged 1-44 yrs. [1]. Understanding how the brain is affected by blunt force trauma is important, but difficult to study directly. Creating a substitute material that mimics the anisotropic properties of white matter in brain tissue is desired to study the behavior of brain tissue during experiments like magnetic resonance elastography (MRE) that inform our understanding of brain mechanics and injury. A previous study [2] about fabricating and characterizing hydrogel lattices via compression and shear testing concluded that geometrical scaling of hydrogel lattices introduced anisotropic qualities similar to that of white matter. The study noted that vintile lattices effectively reproduced anisotropy in the desired direction. One of the lattices, a 10x10x10 mm3 lattice cube, was based on a vintile unit cell with dimensions 2.5x1.25x1.25 mm3, and 0.3mm strut diameter (Fig 1). In this study, vintile lattices were designed, fabricated, and characterized with modified dimensions to soften the hydrogel structure by increasing the size of the unit cell while maintaining the diameter of individual struts. The first unit cell size was increased to 3x1.5x1.5 mm3 and the second unit cell size was increased to 4x2x2 mm3. The motivation is to soften the hydrogel lattice to have a material that is closer to the average elastic modulus of white matter of 2 kPa [3].



    Materials and Methods:: All lattice models were designed in Rhinoceros 3D CAD software (rhino3d.com) with the Grasshopper extension. Using components in Grasshopper, the vintile lattice structure was generated and copied into the Rhino workspace. The lattice shape was then modified (anisotropically scaled) and supports were added for printing (Fig 1.a). Two testing geometries were created: compression-test cube and shear-test disc; each model was printed with the scaled and unscaled lattice. The lattice models were printed using PEGDA StartTM (polyethylene glycol diacrylate, CellInk) resin on a Lumen X Gen 2 Bioprinter. The supports were removed using a sharp razor blade and stored in DI water at 4°C until testing (Fig 1.b). The lattice samples were brought to room temperature before testing. Compression testing and shear testing were performed on a rheometer (HR-20, TA Instruments) using TRIOS software. Data was analyzed in Excel (Fig 1.c-d).

    Results, Conclusions, and Discussions::

    Increasing the unit cell size of the hydrogel lattices from 1.25mm in the X, Y, and Z direction (Fig 1) to 1.5mm, then to 2.0mm, decreased the stiffness of the lattice structure. 


    From the 1.25mm unit cell to the 1.5mm unit cell, the apparent Young’s modulus for the unscaled lattice decreased from 375 to 136 kPa in the Z-direction, from 300 to 106 kPa in the X-direction, and from 350 to 108 kPa in the Y-direction. For the scaled lattice, the apparent Young’s modulus decreased from 200 to 109 kPa in the Z-direction, from 400 to 254 kPa in the X-direction, and from 175 to 78 kPa in the Y-direction. From the 1.25mm unit cell to the 2.0mm unit cell, the apparent Young’s modulus for the unscaled lattice decreased from 375 to 32 kPa in the Z-direction, from 300 to 26 kPa in the X-direction, and from 350 to 27 kPa in the Y-direction. For the scaled lattice, the apparent Young’s modulus decreased from 200 to 17 kPa in the Z-direction, from 400 to 68 kPa in the X-direction, and from 175 to 14 kPa in the Y-direction. A comparison between the 1.25mm, 1.5mm, and 2mm can be seen in Figure 1 where the unscaled lattice directions are E1, E2, and E3 for the Z, X, and Y directions respectively, and the scaled lattice directions are EZ, EX, and EY for their respective directions. 


    For the rheometer tests, the apparent storage modulus was about 32kPa for the 1.5mm scaled disc, 30kPa for the 1.5mm unscaled disc, 7kPa for the 2mm scaled disc, and 10kPa for the 2mm unscaled disc. The apparent loss modulus was about 0.39kPa for the 1.5mm scaled disc, 0.43kPa for the 1.5mm unscaled disc, 0.1kPa for the 2mm scaled disc, and 0.13kPa for the 2mm unscaled disc. 


    A desired modulus that resembles soft tissue in the brain was achieved by tailoring the dimensions of the hydrogel lattice design. Further characterization can be accomplished using magnetic resonance elastography in future studies. MRE uses MR imaging of shear waves to estimate anisotropic mechanical properties [3].



    Acknowledgements (Optional): : Technical support and training from Barbara Semar in the MEMS Shared Instrument Lab, and from colleagues in the Bayly lab. Funding from NIH Grant R01 EB027577 and the Washington University Summer Engineering Fellowship.

    References (Optional): :

    [1] https://braintrauma.org/info/


    [2] Budday, S. et al., 2015. Mechanical properties of gray and white matter brain tissue by indentation. J Mech Behav Biomed Mater 46, 318–330. https://doi.org/10.1016/j.jmbbm.2015.02.024


    [3] Yoon, D. & Ruding, M. et al., 2023. Design and characterization of 3-D printed hydrogel lattices with anisotropic mechanical properties. Journal of the Mechanical Behavior of Biomedical Materials 138, 105652. https://doi.org/10.1016/j.jmbbm.2023.105652