P18 - Selenium-based, Dynamic Poly(ethylene) Glycol Hydrogels Support User-controlled Mechanical Tuning

Saturday, October 11, 2025

10:00 AM - 11:00 AM PDT

Location: Exhibit Hall F, G & H

Presenting Author(s)

AW

Aubrey Williams

Undergraduate Researcher
Syracuse University, United States

Last Author(s)

EJ

Era Jain

Assistant Professor
Syracuse University
Syracuse , New York, United States

Primary Investigator(s)

EJ

Era Jain

Assistant Professor
Syracuse University
Syracuse , New York, United States

Introduction: : Synthetic polyethylene glycol (PEG) hydrogels are one of the most widely used biomaterials due to their biocompatibility and highly tunable nature. While a multitude of bioorthogonal chemistries have been incorporated into PEG hydrogels intended for biological applications, many of these lack reversibility or the ability to be modulated post-fabrication. One of the most recent strategies to produce stimuli-responsive, user-tunable PEG hydrogels has been adapting dynamic covalent chemistries (DCCs), which benefit from the stability of a covalent bond and the ability to rapidly dissociate and re-associate under specific stimuli such as light, pH, or oxidative stress.

Of the DCCs used in PEG hydrogel fabrication, disulfides have enjoyed enduring popularity due to their stability and ease of formation. While hydrogels made using dynamic disulfide bonds offer user-tunable mechanical properties, this high stability results in harsh conditions being required to shift the bond equilibrium. In recent years, the incorporation of selenium as a catalyst for disulfide metathesis has become a common alternative strategy. Since selenium is more electrophilic, selenium sulfide bonds have proven more reactive than pure disulfide bonds, allowing them to be broken under more gentle, physiological conditions.

In this work, we leverage the novel reaction of sodium selenite (Se) and multi-arm PEG thiol (SH) macromers to produce dynamic PEG SH-Se hydrogels with user-tunable mechanical properties. Using rheological analysis, we demonstrate facile tuning of hydrogel stiffness and gelation time through polymer concentration and pH, respectively, and excellent redox-sensitivity through glutathione-mediated softening.

Materials and

Methods: : PEG SH-Se hydrogels were produced using 4-arm PEG-SH and sodium selenite (Se). Briefly, PEG-SH and Se powders were reconstituted at 15% w/v and 1% w/v, respectively, in a 100mM HEPES buffer to control pH. These stocks were then mixed on a parafilm-coated glass plate at a 4:1 SH:Se molar ratio, forming droplets with a total volume of 50 µL. Hydrogels were then covered with glass coverslips to minimize evaporation, and cured in a 37 °C incubator for 30 minutes. Once incubated, all gels were immersed in 1x PBS (pH 7.4) for a minimum of 2 hours before experimentation.
Rheological Characterization: Characterization of PEG hydrogel storage modulus was performed on a DHR-3 rheometer, using 8 mm plate geometry (TA Instruments). To quantify storage modulus, a frequency sweep was conducted at a radial frequency of 0.1-100 rad/s under 1% strain. To demonstrate post-fabrication softening, a time sweep was performed as the hydrogels were immersed in a 10mM glutathione (GSH), 1x PBS solution adjusted to pH 7.4.

Results, Conclusions, and Discussions::

Results: To establish control over initial hydrogel stiffness, we characterized hydrogel mechanical properties at varying polymer concentrations. At concentrations above 2.5%, storage modulus was found to significantly increase as concentration increased (Figure 1A). When exposed to the mild reducing agent GSH, we found that these hydrogels were redox-responsive. Modeling this behavior in 3% w/v PEG SH-Se hydrogels, we observed a 67% decrease in storage modulus after immersion in a 10mM GSH, pH 7.4 solution for 30 minutes (Figure 1B). To determine the sensitivity of hydrogel reaction kinetics to pH, in-situ rheology was conducted using 3% w/v PEG SH-Se hydrogels to monitor gelation (Figure 1C-E). Interestingly, while differences in pH did not affect final storage modulus, lower pH values were associated with a delayed onset of gelation.

Discussion and

Conclusion: We evaluated the reactivity of selenium with disulfides, specifically PEG-SH macromers, to generate selenium crosslinked hydrogels with dynamic, redox-responsive properties. Initial stiffness and gelation time could simply be tuned by modulating polymer concentration and reaction pH. We then assessed the sensitivity of these hydrogels to reducing conditions, finding that they could be significantly degraded using physiologically relevant concentrations of the mild reducing agent GSH. Overall, selenium-disulfide coupling offers a simple and biocompatible strategy for introducing stimuli-responsive mechanical tuning into PEG hydrogels, supporting the development of advanced gel chemistries with improved biofunctionality and cytocompatibility. Additionally, the excellent redox-sensitivity of this system opens the possibility of cell-mediated interactions with our material.

Acknowledgements and/or References (Optional): :