A scalable and tunable thermoreversible polymer for 3D human pluripotent stem cell biomanufacturing

Johnson, Hunter J.; Chakraborty, Saheli; Muckom, Riya; Balsara, Nitash P.; Schaffer, David V.

doi:10.1016/j.isci.2022.104971

Cited by 8 publications

(8 citation statements)

References 34 publications

(57 reference statements)

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“…Nonetheless, this new iEDDA-CSI gelation may benefit light and radical-free hydrogel cross-linking and cell/protein encapsulation. In contrast, the highly tunable and predictable degradation of these hydrogels could be leveraged for autonomous cell/spheroid recovery without using external degradation triggers, such as temperature change or supplying proteases, two common approaches reported in the literature. , In addition, the new iEDDA-CSI assembled and degradable hydrogels may be leveraged for in vivo drug and cell delivery, , since the degradation time is ideal for the stability of protein-based therapeutics which range from days to months in an in vivo setting …”

Section: Resultsmentioning

confidence: 99%

Degradable and Multifunctional PEG-Based Hydrogels Formed by iEDDA Click Chemistry with Stable Click-Induced Supramolecular Interactions

Dimmitt,

Lin

2024

Macromolecules

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The inverse electron demand Diels−Alder (iEDDA) reactions are highly efficient click chemistry increasingly utilized in bioconjugation, live cell labeling, and the synthesis and modification of biomaterials. iEDDA click reactions have also been used to crosslink tetrazine (Tz) and norbornene (NB) modified macromers [e.g., multiarm poly(ethylene glycol) or PEG]. In these hydrogels, Tz-NB adducts exhibit stable supramolecular interactions with a high hydrolytic stability. Toward engineering a new class of PEG-based click hydrogels with highly adaptable properties, we previously reported a new group of NB-derivatized PEG macromers via reacting hydroxyl-terminated PEG with carbic anhydride (CA). In this work, we show that hydrogels cross-linked by PEGNB CA or its derivatives exhibited fast and tunable hydrolytic degradation. Here, we show that PEGNB CA (either mono-or octafunctional) and its dopamine or tyramine conjugated derivatives (i.e., PEGNB-D and PEGNB-T) readily cross-link with 4-arm PEG-Tz to form a novel class of multifunctional iEDDA click hydrogels. Through modularly adjusting the macromers with unstable and stable iEDDA click-induced supramolecular interactions (iEDDA-CSI), we achieved highly tunable degradation, with full degradation in less than 2 weeks to over two months. We also show that secondary enzymatic reactions could dynamically stiffen these hydrogels. These hydrogels could also be spatiotemporally photopatterned through visible light-initiated photochemistry. Finally, the iEDDA-CSI hydrogels post ester hydrolysis displayed shear-thinning and self-healing properties, enabling injectable delivery.

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Section: Resultsmentioning

confidence: 99%

Degradable and Multifunctional PEG-Based Hydrogels Formed by iEDDA Click Chemistry with Stable Click-Induced Supramolecular Interactions

Dimmitt,

Lin

2024

Macromolecules

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“…Finally, hydrogel properties originating from the polymer and crosslinking type can potentially be sensitive and respond differently to various external stimuli, such as pH, ionic strength, and temperature, among other factors. These characteristics can also be tailored to construct stimuli-responsive materials for specific applications, such as thermoreversible gels that can be produced at room or body temperatures [ 17 ].…”

Section: Implications Of Hydrogel Properties On Migrating Cellsmentioning

confidence: 99%

Assessing cell migration in hydrogels: An overview of relevant materials and methods

Solbu

Caballero

Damigos

et al. 2023

Materials Today Bio

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“…In addition, alternative and cheaper culture substrates, such as recombinant fibronectin fragments 112 and hyaluronic acid, are being considered because of the high cost of reported substrates. 113,114…”

Section: Other Materials Improving Aggregate Culturementioning

confidence: 99%

Development of substrates for the culture of human pluripotent stem cells

Kawase

Nakatsuji

2023

Biomater. Sci.

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A scalable and tunable thermoreversible polymer for 3D human pluripotent stem cell biomanufacturing

Cited by 8 publications

References 34 publications

Degradable and Multifunctional PEG-Based Hydrogels Formed by iEDDA Click Chemistry with Stable Click-Induced Supramolecular Interactions

Degradable and Multifunctional PEG-Based Hydrogels Formed by iEDDA Click Chemistry with Stable Click-Induced Supramolecular Interactions

Assessing cell migration in hydrogels: An overview of relevant materials and methods

Development of substrates for the culture of human pluripotent stem cells

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