Design of Hydrolytically Resorbable and Biocompatible Polyethylene Glycol Crosslinkers for Facile Control of Hydrogel Degradation

Kroger, Stephanie M.; Hill, Lindsay; Jain, Era; Stock, Aaron A.; Bracher, Paul J.; He, Fahu; Zustiak, Silviya Petrova

doi:10.2139/ssrn.3441947

Cited by 2 publications

(5 citation statements)

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“…Note that the majority of microspheres were degraded at 25 days of incubation, as indicated by the low number of microspheres observed within the same volume, and that microspheres lost their integrity prior to complete degradation (inset in Figure A). As expected, PEG hydrogel microspheres exhibited similar swelling behavior and degradation kinetics as slab geometry PEG hydrogels. ,,, Both swelling and degradation are dependent on the cross-link density of the hydrogel matrix, with a lower cross-linking density leading to increased swelling and degradation. , The similar swelling and degradation (microspheres persisted over >20 days) to slab hydrogels indicate that complete mixing of precursor solutions was achieved within the device, leading to efficient cross-linking.…”

Section: Resultssupporting

confidence: 64%

“…As expected, PEG hydrogel microspheres exhibited similar swelling behavior and degradation kinetics as slab geometry PEG hydrogels. 6,29,33,63 Both swelling and degradation are dependent on the cross-link density of the hydrogel matrix, with a lower cross-linking density leading to increased swelling and degradation. 51,64 The similar swelling and degradation (microspheres persisted over >20 days) to slab hydrogels indicate that complete mixing of precursor solutions was achieved within the device, leading to efficient cross-linking.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

“…Here, we designed a dual aqueous stream microfluidic chip device to effectively mix hydrogel precursor solutions in situ to produce monodisperse polyethylene glycol (PEG) hydrogel microspheres that gel via a Michael-type addition cross-linking reaction, a timed gelation mechanism. PEG hydrogels are useful for therapeutic applications due to their bioinertness, biopreservation, immunoprotection, and versatility. ,, PEG macromers and cross-linkers can be modified by adding functional moieties to the PEG backbone, enabling fine-tuning of the physical, mechanical, and biochemical properties and degradation rates. − Several mixing mechanisms were considered and optimized to ensure that hydrogel precursor solutions were properly mixed prior to droplet formation. The benefit of such dual aqueous stream microfluidic device is in situ mixing of hydrogel precursor solutions and subsequent hydrogel microsphere formation all on one chip.…”

Section: Introductionmentioning

confidence: 99%

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Microfluidic Chip Device for In Situ Mixing and Fabrication of Hydrogel Microspheres via Michael-Type Addition

et al. 2021

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Hydrogel microspheres are sought for a variety of biomedical applications, including therapeutic and cellular delivery, sensors, and lubricants. Robust fabrication of hydrogel microspheres with uniform sizes and properties can be achieved using microfluidic systems that rely on droplet formation and subsequent gelation to form microspheres. Such systems work well when gelation is initiated after droplet formation but are not practical for timed gelation systems where gelation is initiated prior to droplet formation; premature gelation can lead to device blockage, variable microsphere diameter due to viscosity changes in the precursor solution, and limited numbers of microspheres produced in a single run. To enable microfluidic fabrication of microspheres from timed gelation hydrogel systems, an in situ mixing region is needed so that various hydrogel precursor components can be added separately. Here, we designed and evaluated three mixing devices for their effectiveness at mixing hydrogel precursor solutions prior to droplet formation and subsequent gelation. The serpentine geometry was found to be the most effective and was further improved with the inclusion of a pillar array to increase agitation. The optimized device was shown to fully mix precursor solutions and enable the fabrication of monodisperse polyethylene glycol microspheres, offering great potential for use with timed gelation hydrogel systems.

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Section: Resultssupporting

confidence: 64%

Section: ■ Results and Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Microfluidic Chip Device for In Situ Mixing and Fabrication of Hydrogel Microspheres via Michael-Type Addition

et al. 2021

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“…Hydrogel-based delivery devices have emerged as a method to slow therapeutic release while preserving therapeutic activity. , The nanoporous structure of the hydrogels allows for hindered diffusion, thereby prolonging therapeutic release and increasing the duration of therapeutic effect compared to bolus doses . Diffusion of therapeutics from hydrogels can be moderately controlled by modulating the hydrogel mesh size, swelling properties, and stiffness . However, while hydrogels are suitable delivery devices for large molecules, small molecules can easily diffuse out of the hydrogel due to their smaller size compared to the hydrogel mesh size, leading to a high initial burst release, short release duration, and reduced clinical efficacy …”

Section: Introductionmentioning

confidence: 99%

“…5 Diffusion of therapeutics from hydrogels can be moderately controlled by modulating the hydrogel mesh size, swelling properties, and stiffness. 6 However, while hydrogels are suitable delivery devices for large molecules, small molecules can easily diffuse out of the hydrogel due to their smaller size compared to the hydrogel mesh size, leading to a high initial burst release, short release duration, and reduced clinical efficacy. 7 Several methods have been explored to enhance the efficacy of hydrogel therapeutic delivery by minimizing burst release, including tethering of therapeutics, the formation of "smart" hydrogels, and the incorporation of nanomaterials.…”

Section: ■ Introductionmentioning

confidence: 99%

Silicate Clay-Hydrogel Nanoscale Composites for Sustained Delivery of Small Molecules

Khachani

Stealey

Dharmesh

et al. 2022

ACS Appl. Nano Mater.

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Hydrogels have been widely used for therapeutic delivery applications due to their tunability and biocompatibility, although delivery of small molecules is difficult due to high burst release and rapid diffusion from the device. Nanosilicate clays (nanoclays) have shown the adsorption potential of small molecules, offering a lever to prolong the release kinetics of hydrogel delivery devices. However, further characterization of small molecule–nanoclay interactions and their effect on molecule release is needed to allow for the custom design of tunable nanocomposite hydrogel delivery devices. Here, we have characterized the adsorption of small molecules onto three nanoclays, Laponite, montmorillonite, and halloysite, and monitored their release in various conditions. The layered structures of Laponite and montmorillonite led to cationic exchange of the small molecules into the interlayer space, whereas the small molecules were adsorbed onto the surface of the tubular halloysite. The addition of nanoclays to polyethylene glycol (PEG) hydrogels significantly slowed the release of small molecules, especially from Laponite (500-fold decrease) and montmorillonite (∼3000-fold decrease) composite gels. Cationic small molecules were shown to be released significantly slower from nanocomposite hydrogels than anionic ones. The incubation time of small molecules with nanoclays prior to hydrogel encapsulation also played a key role in determining their release rate, with montmorillonite showing near-immediate adsorption while halloysite exhibited a higher dependence on incubation time due to slower adsorption kinetics. Release buffer salt concentration and pH were shown to affect release kinetics due to modulation of nanoclay–small molecule interactions. These results show the potential for formation of a highly tunable nanocomposite hydrogel delivery device for a greatly prolonged release of small molecules compared to traditional hydrogels.

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Design of Hydrolytically Resorbable and Biocompatible Polyethylene Glycol Crosslinkers for Facile Control of Hydrogel Degradation

Cited by 2 publications

References 0 publications

Microfluidic Chip Device for In Situ Mixing and Fabrication of Hydrogel Microspheres via Michael-Type Addition

Microfluidic Chip Device for In Situ Mixing and Fabrication of Hydrogel Microspheres via Michael-Type Addition

Silicate Clay-Hydrogel Nanoscale Composites for Sustained Delivery of Small Molecules

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