Browsing by Subject "Polyethylene glycols"

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    Heparinized Gelatin-Based Hydrogels for Differentiation of Induced Pluripotent Stem Cells
    (American Chemical Society, 2022) Arkenberg, Matthew R.; Koehler, Karl; Lin, Chien-Chi; Biomedical Engineering, School of Engineering and Technology
    Chemically defined hydrogels are increasingly utilized to define the effects of extracellular matrix (ECM) components on cellular fate determination of human embryonic and induced pluripotent stem cell (hESC and hiPSCs). In particular, hydrogels cross-linked by orthogonal click chemistry, including thiol-norbornene photopolymerization and inverse electron demand Diels-Alder (iEDDA) reactions, are explored for 3D culture of hESC/hiPSCs owing to the specificity, efficiency, cytocompatibility, and modularity of the cross-linking reactions. In this work, we exploited the modularity of thiol-norbornene photopolymerization to create a biomimetic hydrogel platform for 3D culture and differentiation of hiPSCs. A cell-adhesive, protease-labile, and cross-linkable gelatin derivative, gelatin-norbornene (GelNB), was used as the backbone polymer for constructing hiPSC-laden biomimetic hydrogels. GelNB was further heparinized via the iEDDA click reaction using tetrazine-modified heparin (HepTz), creating GelNB-Hep. GelNB or GelNB-Hep was modularly cross-linked with either inert macromer poly(ethylene glycol)-tetra-thiol (PEG4SH) or another bioactive macromer-thiolated hyaluronic acid (THA). The formulations of these hydrogels were modularly tuned to afford biomimetic matrices with similar elastic moduli but varying bioactive components, enabling the understanding of each bioactive component on supporting hiPSC growth and ectodermal, mesodermal, and endodermal fate commitment under identical soluble differentiation cues.
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    Probing osteocyte function in gelatin hydrogels with tunable viscoelasticity
    (American Chemical Society, 2021) Nguyen, Han D.; Sun, Xun; Yokota, Hiroki; Lin, Chien-Chi; Biomedical Engineering, School of Engineering and Technology
    Bone is an attractive site for metastatic cancer cells and has been considered as "soil" for promoting tumor growth. However, accumulating evidence suggests that some bone cells (e.g., osteocytes) can actually suppress cancer cell migration and invasion via direct cell-cell contact and/or through cytokine secretion. Toward designing a biomimetic niche for supporting 3D osteocyte culture, we present here a gelatin-based hydrogel system with independently tunable matrix stiffness and viscoelasticity. In particular, we synthesized a bifunctional macromer, gelatin-norbornene-boronic acid (i.e., GelNB-BA), for covalent cross-linking with multifunctional thiol linkers [e.g., four-arm poly(ethylene glycol)-thiol or PEG4SH] to form thiol-NB hydrogels. The immobilized BA moieties in the hydrogel readily formed reversible boronate ester bonds with 1,3-diols on physically entrapped poly(vinyl alcohol) (PVA). Adjusting the compositions of GelNB-BA, PEG4SH, and PVA afforded hydrogels with independently tunable elasticity and viscoelasticity. With this new dynamic hydrogel platform, we investigated matrix mechanics-induced growth and cytokine secretion of encapsulated MLO-A5 pre-osteocytes. We discovered that more compliant or viscoelastic gels promoted A5 cell growth. On the other hand, cells encapsulated in stiffer gels secreted higher amounts of pro-inflammatory cytokines and chemokines. Finally, conditioned media (CM) collected from the encapsulated MLO-A5 cells (i.e., A5-CM) strongly inhibited breast cancer cell proliferation, invasion, and expression of tumor-activating genes. This new biomimetic hydrogel platform not only serves as a versatile matrix for investigating mechano-sensing in osteocytes but also provides a means to produce powerful anti-tumor CM.