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A Diffusion-Reaction Model for Predicting Enzyme-Mediated Dynamic Hydrogel Stiffening

1
Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN 47907, USA
2
Department of Biomedical Engineering, Purdue School of Engineering & Technology, Indiana University-Purdue University Indianapolis, Indianapolis, IN 46202, USA
*
Author to whom correspondence should be addressed.
Received: 30 January 2019 / Revised: 1 March 2019 / Accepted: 6 March 2019 / Published: 13 March 2019
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Abstract

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. View Full-Text
Keywords: diffusion-reaction; dynamic hydrogel; matrix stiffening; tyrosinase diffusion-reaction; dynamic hydrogel; matrix stiffening; tyrosinase
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Liu, H.-Y.; Lin, C.-C. A Diffusion-Reaction Model for Predicting Enzyme-Mediated Dynamic Hydrogel Stiffening. Gels 2019, 5, 17.

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