Photo-induced viscoelasticity in cytocompatible hydrogel substrates

Abstract

Human mesenchymal stem cells (hMSCs) sense and respond to the bulk elastic and viscoelastic properties of their microenvironment, as well as the spatial distribution of these mechanical signals.Hydrogel substrates with photo-controlled mechanical properties can allow one to probe the cellular response to localized variations in substrate viscoelasticity. Here, we report on a cytocompatible hydrogel culture system that allows photo-induced changes in viscoelasticity via an additionfragmentation chain transfer reaction triggered by a network tethered photoinitiator. Tethering the photoinitiator to the network allowed for on-demand material property changes and spatiotemporal control of viscoelasticity. It was found that both the photoinitiation rate and chain transfer agent concentration contributed to the degree of photo-induced viscoelasticity. The loss factor (tan δ) of this system was tuned with the illumination intensity and chain transfer agent concentration, with a maximum value of 0.27 at 1 rad s -1 . In experiments with hMSCs cultured on the hydrogels, the cellular protrusions retracted in response to photo-induced viscoelasticity and this retraction could be confined to a single cellular protrusion through controlled photo-illumination. The retraction length and area of each protrusion was dependent on the initial proximity to the viscoelastic region.

Viscoelastic Cell Microenvironment: Hydrogel‐Based Strategy for Recapitulating Dynamic ECM Mechanics

“…Besides physically crosslinked hydrogels, the hydrogels containing dynamic covalent chemistries, such as thioester, [ 47,175–177 ] allyl sulfide, [ 178 ] disulfide, [ 158 ] hydrazone, [ 48,179,180 ] boronate, [ 49,50,181 ] oxime, [ 182–184 ] Schiff base, [ 185–187 ] and Diel–Alder [ 188–190 ] that create covalent adaptable networks can also possess viscoelasticity. Thioester‐containing hydrogels were fabricated via thiol‐ene click chemistry to yield adaptable networks ( Figure A).…”

3D Patterning within Hydrogels for the Recreation of Functional Biological Environments

“…As an example, allyl sulfide moieties in hydrogels can act as on‐off switches to trigger the sequential exchange of biochemical cues employing the chain transfer reaction of a thiyl radical. [ 198 ] Other examples have demonstrated the possibility to generate hydrogels with tunable viscoelastic [ 199 ] and cell release [ 200 ] properties on‐demand. The chain exchange offered by the allyl sulfide functional group is limited to the consumption of the activating radical spices.…”

Engineered Biomaterial Platforms to Study Fibrosis

“…(d) Reproduced with permission under the terms of the CC‐BY‐3.0 license. [ 99 ] Copyright 2019, the Authors. Published by IOP Publishing.…”

“…[ 98 ] Similarly, PEG hydrogels with phototunable viscoelasticity showed that the introduction of local areas of viscoelasticity induces rapid retraction of MSC protrusions, suggesting that subcellular‐sized areas of viscoelasticity may determine cell phenotype (Figure 4). [ 99 ] The effects of tissue viscoelasticity, unlike stiffness, are not straightforward and it is likely that the specific ECM factors that contribute to tissue viscoelasticity and ECM storage modulus determine cellular responses to viscoelasticity. [ 100 ] Additionally, further characterization of viscoelastic hydrogels need to be carried out and clearly described as some materials display viscoplastic behavior, [ 65 ] while others do not have plastic behavior within the cell force‐relevant regime.…”