Shear Thickening Behavior in Injectable Tetra-PEG Hydrogels Cross-Linked via Dynamic Thia-Michael Addition Bonds

Crowell, Anne D.; FitzSimons, Thomas M.; Anslyn, Eric V.; Schultz, Kelly M.; Rosales, Adrianne M.

doi:10.1021/acs.macromol.3c00780

Cited by 5 publications

(9 citation statements)

References 72 publications

(204 reference statements)

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“…Injectability is often associated with shear thinning behavior in reversibly cross-linked hydrogels . However, injectable tetra-PEG hydrogels with thia-conjugate addition cross-links exhibit complex rheological behavior: shear thickening occurs at low shear rates, followed by flow instability at slightly higher shear rates with shear thinning-type behavior . Nevertheless, these hydrogels are injectable, and the material properties at shear rates relevant to injection can be estimated by approximating a syringe and needle as a capillary rheometer. , With this approach, injection force measurements were made at several flow rates and the apparent shear rate, shear stress, and apparent viscosity were calculated at the needle wall (Section S6).…”

Section: Resultsmentioning

confidence: 99%

Photothermal Modulation of Dynamic Covalent Poly(ethylene glycol)/PEDOT Composite Hydrogels for On-Demand Drug Delivery

Thapa,

FitzSimons,

Otakpor

et al. 2023

ACS Appl. Mater. Interfaces

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Hydrogels are cross-linked three-dimensional polymer networks that have tissue-like properties. Dynamic covalent bonds (DCB) can be utilized as hydrogel cross-links to impart injectability, self-healing ability, and stimuli responsiveness to these materials. In our research, we utilized dynamic thiol-Michael bonds as cross-links in poly(ethylene glycol) (PEG)-based hydrogels. Because the equilibrium of the reversible, exothermic thiol-Michael reaction can be modulated by temperature, we investigated the possibility of using thermal and photothermal stimuli to modulate the gel-to-sol transition of these materials with the aim of developing an on-demand pulsatile cargo release system. For this purpose, we incorporated poly(3,4-ethylenedioxythiophene) (PEDOT) nanoparticles within the hydrogel to facilitate photothermal modulation using near-infrared light. PEDOT nanoparticles of 50 nm in diameter and with strong near-infrared absorption were prepared by oxidative emulsion polymerization. We then used Michael addition of thiol−ene pairs from 4-arm PEG-thiol (PEG-SH) and 4-arm PEG-benzylcyanoacetamide (PEG-BCA) to form dynamically cross-linked hydrogels. PEDOT nanoparticles were entrapped in situ to form Gel/PEDOT composites. Rheology and inverted tube test studies showed that the gel-to-sol transition occurred at 45−50 °C for 5 wt % gels and that this transition could be tailored by varying the wt % of the polymer precursors. The hydrogels were found to be capable of self-healing and being injected with a clinically relevant injection force. Bovine serum albumin-fluorescein isothiocyanate (BSA-FITC), a fluorescently labeled protein, was then loaded into the Gel/PEDOT as a therapeutic mimic. Increased release of BSA-FITC upon direct thermal stimulation and photothermal stimulation with an 808 nm laser was observed. Pulsatile release of BSA-FITC over seven cycles was demonstrated. MTS and live−dead assays demonstrated that Gel/PEDOT was cytocompatible in MDA-MB-231 breast cancer and 3T3 fibroblast cell lines. Further studies demonstrated that the encapsulation and laser-triggered release of the chemotherapeutic agent doxorubicin (DOX) could also be achieved. Altogether, this work advances our understanding of the temperature-dependent behavior of a dynamic covalent hydrogel, Gel/PEDOT, and leverages that understanding for application as a photothermally responsive biomaterial for controlled release.

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Section: Resultsmentioning

confidence: 99%

Photothermal Modulation of Dynamic Covalent Poly(ethylene glycol)/PEDOT Composite Hydrogels for On-Demand Drug Delivery

Thapa,

FitzSimons,

Otakpor

et al. 2023

ACS Appl. Mater. Interfaces

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“…Shear-thickening behavior has also been observed in hydrogels prepared from 4-arm PEG macromers with dynamic-covalent Thia-Michael cross-links. 73 These hydrogels displayed a low-shear plateau followed by a region of shear-thickening, which was primarily attributed to chain stretching. Following the shear-thickening regime, these gels displayed flow instability, which limited the range of shear rates experimentally available.…”

Section: Strain-dependent Stress Relaxationmentioning

confidence: 99%

“…In contrast, if chain stretching were primarily responsible for shear-thickening in these gels, no hysteresis would be expected, and reversibility of thickening in the low-shear regime would be observed. 73 Shear rate sweeps were also performed at temperatures ranging from 15 to 45 °C (Figure S11A). Viscosity was normalized by the low shear rate viscosity (η/η 0 ) and plotted as a function of shear rate (Figure S11B).…”

Section: Strain-dependent Stress Relaxationmentioning

confidence: 99%

“…Similarly, it is anticipated that the shear-thickening behavior exhibited by these gels is a result of shear-induced chain alignment and an increase in hydrogen bonding. 67,72,73,77 This results in an increase in stiffness prior to shear-thinning. Accordingly, it is expected that shear-thinning results primarily from the rupture of boronate ester cross-links at high shear rates.…”

Section: Strain-dependent Stress Relaxationmentioning

confidence: 99%

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Strain-Stiffening Mechanoresponse in Dynamic-Covalent Cellulose Hydrogels

Ollier,

Webber

2024

Biomacromolecules

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Mechanical stimuli such as strain, force, and pressure are pervasive within and beyond the human body. Mechanoresponsive hydrogels have been engineered to undergo changes in their physicochemical or mechanical properties in response to such stimuli. Relevant responses can include strain-stiffening, selfhealing, strain-dependent stress relaxation, and shear rate-dependent viscosity. These features are a direct result of dynamic bonds or noncovalent/physical interactions within such hydrogels. The contributions of various types of bonds and intermolecular interactions to these behaviors are important to more fully understand the resulting materials and engineer their mechanoresponsive features. Here, strain-stiffening in carboxymethylcellulose hydrogels cross-linked with pendant dynamic-covalent boronate esters using tannic acid is studied and modulated as a function of polymer concentration, temperature, and effective cross-link density. Furthermore, these materials are found to exhibit self-healing and strain-memory, as well as strain-dependent stress relaxation and shear rate-dependent changes in gel viscosity. These features are attributed to the dynamic nature of the boronate ester cross-links, interchain hydrogen bonding and bundling, or a combination of these two intermolecular interactions. This work provides insight into the interplay of such interactions in the context of mechanoresponsive behaviors, particularly informing the design of hydrogels with tunable strain-stiffening. The multiresponsive and tunable nature of this hydrogel system therefore presents a promising platform for a variety of applications.

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“…In particular, benzalcyanoacetate/acetamide (BCA/BCAm) and benzalisoxazolone (BiOX) tM acceptors have been developed to undergo dynamic exchange with thiols under ambient conditions (in polar environments), without the need for catalysts (Figure b). − A signature feature of these species is their strong sensitivity to electronic modifications at the β-phenyl position, with increasing electron-withdrawing character leading to higher values of the equilibrium constant ( K eq ). This key ability to tune the equilibrium position of BCA/BCAm moieties has been leveraged to prepare a range of materials from hydrogels − to responsive dense suspensions , with user designed properties. Notably, when prepared as bulk films, BCA-based materials can exhibit an emergent phase separation phenomenon, coined dynamic reaction-induced phased separation (DRIPS), leading to robust mechanical properties despite their ambient dynamic exchange and their relatively low values of K eq (≈10 M –1 to 1000 M –1 ) .…”

mentioning

confidence: 99%

Connecting Molecular Exchange Dynamics to Stress Relaxation in Phase-Separated Dynamic Covalent Networks

Dolinski,

Tao,

Boynton

et al. 2024

ACS Macro Lett.

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A suite of phase separated dynamic covalent networks based on highly tunable dynamic benzalcyanoacetate (BCA) thia-Michael acceptors are investigated. In situ kinetic studies on small molecule model systems are used in conjunction with macroscopic characterization of phase stability and stress relaxation to understand how the molecular dynamics relate to relaxation modes. Electronic modification of the BCA unit strongly impacts the exchange dynamics (particularly the rate of dissociation) and the overall equilibrium constant (K eq ) of the system, with electron-withdrawing groups leading to decreased dissociation rate and increased K eq . Critically, below a chemistry-defined temperature cutoff (related to the stability of the hard phase domains), the stress relaxation behavior of these phase separated materials is dominated by the molecular exchange dynamics, allowing for networks with a tailored thermomechanical response.

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Shear Thickening Behavior in Injectable Tetra-PEG Hydrogels Cross-Linked via Dynamic Thia-Michael Addition Bonds

Cited by 5 publications

References 72 publications

Photothermal Modulation of Dynamic Covalent Poly(ethylene glycol)/PEDOT Composite Hydrogels for On-Demand Drug Delivery

Photothermal Modulation of Dynamic Covalent Poly(ethylene glycol)/PEDOT Composite Hydrogels for On-Demand Drug Delivery

Strain-Stiffening Mechanoresponse in Dynamic-Covalent Cellulose Hydrogels

Connecting Molecular Exchange Dynamics to Stress Relaxation in Phase-Separated Dynamic Covalent Networks

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