Browsing by Subject "Dynamic hydrogel"

Now showing 1 - 2 of 2
  • Thumbnail Image
    Item
    A Diffusion-Reaction Model for Predicting Enzyme-Mediated Dynamic Hydrogel Stiffening
    (MDPI, 2019-03-13) Liu, Hung-Yi; Lin, Chien-Chi; Biomedical Engineering, School of Engineering and Technology
    Hydrogels with spatiotemporally tunable mechanical properties have been increasingly employed for studying the impact of tissue mechanics on cell fate processes. These dynamic hydrogels are particularly suitable for recapitulating the temporal stiffening of a tumor microenvironment. To this end, we have reported an enzyme-mediated stiffening hydrogel system where tyrosinase (Tyrase) was used to stiffen orthogonally crosslinked cell-laden hydrogels. Herein, a mathematical model was proposed to describe enzyme diffusion and reaction within a highly swollen gel network, and to elucidate the critical factors affecting the degree of gel stiffening. Briefly, Fick's second law of diffusion was used to predict enzyme diffusion in a swollen poly(ethylene glycol) (PEG)-peptide hydrogel, whereas the Michaelis⁻Menten model was employed for estimating the extent of enzyme-mediated secondary crosslinking. To experimentally validate model predictions, we designed a hydrogel system composed of 8-arm PEG-norbornene (PEG8NB) and bis-cysteine containing peptide crosslinker. Hydrogel was crosslinked in a channel slide that permitted one-dimensional diffusion of Tyrase. Model predictions and experimental results suggested that an increasing network crosslinking during stiffening process did not significantly affect enzyme diffusion. Rather, diffusion path length and the time of enzyme incubation were more critical in determining the distribution of Tyrase and the formation of additional crosslinks in the hydrogel network. Finally, we demonstrated that the enzyme-stiffened hydrogels exhibited elastic properties similar to other chemically crosslinked hydrogels. This study provides a better mechanistic understanding regarding the process of enzyme-mediated dynamic stiffening of hydrogels.
  • Thumbnail Image
    Item
    Dynamic PEG-Peptide Hydrogels via Visible Light and FMN-Induced Tyrosine Dimerization
    (Wiley, 2018) Liu, Hung-Yi; Nguyen, Han D.; Lin, Chien-Chi; Biomedical Engineering, School of Engineering and Technology
    Photo-responsive hydrogels have become invaluable three-dimensional (3D) culture matrices for mimicking aspects of extracellular matrix (ECM). Recent efforts have focused on using ultraviolet (UV) light exposure and multifunctional macromers to induce secondary hydrogel crosslinking and dynamic matrix stiffening in the presence of cells. This contribution reports the design of a novel yet simple dynamic poly(ethylene glycol)-peptide hydrogel system through flavin mononucleotide (FMN) induced di-tyrosine crosslinking. These di-tyrosine linkages effectively increase hydrogel crosslinking density and elastic modulus. In addition, the degree of stiffening in hydrogels at a fixed PEG macromer content can be readily tuned by controlling FMN concentration or the number of tyrosine residues built-in to the peptide linker. Furthermore, tyrosine-bearing pendant biochemical motifs could be spatial-temporally patterned in the hydrogel network via controlling light exposure through a photomask. The visible light and FMN induced tyrosine dimerization process produces cytocompatible and physiologically relevant degree of stiffening, as shown by changes of cell morphology and gene expression in pancreatic cancer and stromal cells. This new dynamic hydrogel scheme should be highly desirable for researchers seeking a photo-responsive hydrogel system without complicated chemical synthesis and secondary UV light irradiation.