Guest–host interlinked PEG-MAL granular hydrogels as an engineered cellular microenvironment

Widener, Adrienne E.; Bhatta, Mallika; Angelini, Thomas E.; Phelps, Edward A.

doi:10.1039/d0bm01499k

Cited by 32 publications

(55 citation statements)

References 68 publications

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“…To date, these systems have relied on physical interactions such as ionic attraction, metal-ligand coordination, guest-host assembly, and hydrogen bonding. [19,[33][34][35][36][37] For example, Hsu et al combined positively-charged chitosan and negatively-charged gelatin microgels into an injectable granular hydrogel for neural tissue engineering applications. [34] The addition of the reversible ionic inter-particle interactions resulted in at least a fivefold increase in storage modulus compared to neutrally charged controls, while still maintaining shear-thinning and self-healing behavior.…”

Section: Introductionmentioning

confidence: 99%

Sticking Together: Injectable Granular Hydrogels with Increased Functionality via Dynamic Covalent Inter‐Particle Crosslinking

Muir

Qazi

Weintraub

et al. 2022

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Granular hydrogels are an exciting class of microporous and injectable biomaterials that are being explored for many biomedical applications, including regenerative medicine, 3D printing, and drug delivery. Granular hydrogels often possess low mechanical moduli and lack structural integrity due to weak physical interactions between microgels. This has been addressed through covalent inter‐particle crosslinking; however, covalent crosslinking often occurs through temporal enzymatic methods or photoinitiated reactions, which may limit injectability and material processing. To address this, a hyaluronic acid (HA) granular hydrogel is developed with dynamic covalent (hydrazone) inter‐particle crosslinks. Extrusion fragmentation is used to fabricate microgels from photocrosslinkable norbornene‐modified HA, additionally modified with either aldehyde or hydrazide groups. Aldehyde and hydrazide‐containing microgels are mixed and jammed to form adhesive granular hydrogels. These granular hydrogels possess enhanced mechanical integrity and shape stability over controls due to the covalent inter‐particle bonds, while maintaining injectability due to the dynamic hydrazone bonds. The adhesive granular hydrogels are applied to 3D printing, which allows the printing of structures that are stable without any further post‐processing. Additionally, the authors demonstrate that adhesive granular hydrogels allow for cell invasion in vitro. Overall, this work demonstrates the use of dynamic covalent inter‐particle crosslinking to enhance injectable granular hydrogels.

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Section: Introductionmentioning

confidence: 99%

Sticking Together: Injectable Granular Hydrogels with Increased Functionality via Dynamic Covalent Inter‐Particle Crosslinking

Muir

Qazi

Weintraub

et al. 2022

Small

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“…Ad-SH and CD-SH, alone or in combination have been utilized to introduce GH functionality to hydrogels, but in different contexts to our approach. [24][25][26] Supramolecular hydrogels have also been formed by radical copolymerization of inclusion complexes with acrylamide; however, to keep the two networks within IPNs distinct and prevent reactions with MeHA, radical polymerizations of guest-host monomers were avoided. [27] In our design, all reagents (MeHA, NorHA, Ad-SH, CD-SH) are mixed together along with photoinitiator (lithium phenyl-2,4,6trimethylbenzoylphosphinate, LAP) and reacted via visible light (400-500 nm) exposure to transition a nonviscous solution into an IPN hydrogel (Figure 1c).…”

Section: Design and Synthesis Of Ipn Hydrogels Via A One-pot Reactionmentioning

confidence: 99%

Simultaneous One‐Pot Interpenetrating Network Formation to Expand 3D Processing Capabilities

et al. 2022

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The incorporation of a secondary network into traditional single‐network hydrogels can enhance mechanical properties, such as toughness and loading to failure. These features are important for many applications, including as biomedical materials; however, the processing of interpenetrating polymer network (IPN) hydrogels is often limited by their multistep fabrication procedures. Here, a one‐pot scheme for the synthesis of biopolymer IPN hydrogels mediated by the simultaneous crosslinking of two independent networks with light, namely: i) free‐radical crosslinking of methacrylate‐modified hyaluronic acid (HA) to form the primary network and ii) thiol–ene crosslinking of norbornene‐modified HA with thiolated guest–host assemblies of adamantane and β‐cyclodextrin to form the secondary network, is reported. The mechanical properties of the IPN hydrogels are tuned by changing the network composition, with high water content (≈94%) hydrogels exhibiting excellent work of fracture, tensile strength, and low hysteresis. As proof‐of‐concept, the IPN hydrogels are implemented as low‐viscosity Digital Light Processing resins to fabricate complex structures that recover shape upon loading, as well as in microfluidic devices to form deformable microparticles. Further, the IPNs are cytocompatible with cell adhesion dependent on the inclusion of adhesive peptides. Overall, the enhanced processing of these IPN hydrogels will expand their utility across applications.

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“…Because the mechanism exploits hydrophobic interactions, these hydrogels self-assemble in water but easily disassemble under shear stress [ 82 , 83 ]. This method has primarily been used with adamantane- and β-cyclodextrin-modified HA, but it has recently been employed by the Phelps group to anneal PEG microgels [ 84 ].…”

Section: Commonly Used Materialsmentioning

confidence: 99%

Reductionist Three-Dimensional Tumor Microenvironment Models in Synthetic Hydrogels

Katz

West

2022

Cancers

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The tumor microenvironment (TME) plays a determining role in everything from disease progression to drug resistance. As such, in vitro models which can recapitulate the cell–cell and cell–matrix interactions that occur in situ are key to the investigation of tumor behavior and selecting effective therapeutic drugs. While naturally derived matrices can retain the dimensionality of the native TME, they lack tunability and batch-to-batch consistency. As such, many synthetic polymer systems have been employed to create physiologically relevant TME cultures. In this review, we discussed the common semi-synthetic and synthetic polymers used as hydrogel matrices for tumor models. We reviewed studies in synthetic hydrogels which investigated tumor cell interactions with vasculature and immune cells. Finally, we reviewed the utility of these models as chemotherapeutic drug-screening platforms, as well as the future directions of the field.

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Guest–host interlinked PEG-MAL granular hydrogels as an engineered cellular microenvironment

Abstract: We report the development of a polyethylene glycol (PEG) hydrogel scaffold that provides the advantages of conventional bulk PEG hydrogels for engineering cellular microenvironments and allows for rapid cell migration.

Cited by 32 publications

References 68 publications

Sticking Together: Injectable Granular Hydrogels with Increased Functionality via Dynamic Covalent Inter‐Particle Crosslinking

Sticking Together: Injectable Granular Hydrogels with Increased Functionality via Dynamic Covalent Inter‐Particle Crosslinking

Simultaneous One‐Pot Interpenetrating Network Formation to Expand 3D Processing Capabilities

Reductionist Three-Dimensional Tumor Microenvironment Models in Synthetic Hydrogels

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