Sequential Thiol–Ene and Tetrazine Click Reactions for the Polymerization and Functionalization of Hydrogel Microparticles

Jivan, Faraz; Yegappan, Ramanathan; Pearce, Hannah A.; Carrow, James K.; McShane, Michael J.; Gaharwar, Akhilesh K.; Alge, Daniel L.

doi:10.1021/acs.biomac.6b00990

Cited by 58 publications

(60 citation statements)

References 55 publications

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“…Hydrogels are water-swollen network biomaterialsw ith applications in cell encapsulation and drug delivery. [121,122] Doublenetwork hydrogels are some of the strongest synthetic soft materials. However,t hey are, in general,d ifficult to synthesize, and free-radical polymerization and the use of toxic starting materials are often required.…”

Section: Hydrogelsmentioning

confidence: 99%

Inverse‐Electron‐Demand Diels–Alder Reactions: Principles and Applications

Png

Zeng

et al. 2017

Chemistry An Asian Journal

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Inverse-electron-demand Diels-Alder (iEDDA) reactions are an intriguing class of cycloaddition reactions that have attracted increasing attention for their application in bioorthogonal chemistry, the total synthesis of natural products, and materials science. In many cases, the application of the iEDDA reaction has been demonstrated as an innovative approach to achieve target structures. The theoretical aspects of this class of reactions are of particular interest for scientists as a means to understand the various factors, such as steric strain and electron density of the attached groups, that govern the reaction and thus to elucidate the reaction mechanism. This review aims to summarize both theoretical investigations and application-driven research work on the iEDDA reaction. First, the historical aspects and the theoretical basis of the reaction, especially recent advances in time-dependent density functional theory (TD-DFT) calculations, as well as catalysis strategies will be highlighted and discussed. Second, the applications of this novel reaction in the context of materials science, bioorthogonal chemistry, and total synthesis of natural products will be elaborated with selected recent examples. The challenges and opportunities of the iEDDA reaction will be highlighted to give more insight into its potential applications in many other research areas.

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Section: Hydrogelsmentioning

confidence: 99%

Inverse‐Electron‐Demand Diels–Alder Reactions: Principles and Applications

Png

Zeng

et al. 2017

Chemistry An Asian Journal

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“…The Shen group investigated injectable hydrogels based on the modified PEG for sustaining doxorubicin released [23,24], but the use of a metal catalyst was required in the modification route of PEG. Other researchers exploited the IEDDA reaction between Tz and dienophiles for the development of hydrogels [14,[25][26][27]. For instance, Alge et al [14] synthesized hydrogels for three-dimensional cell culture using four-arm PEG functionalized with Tz and peptides cross-linker functionalized with norbornene (Nb).…”

mentioning

confidence: 99%

Click-cross-linked, doxorubicin-loaded hydrogels based on poly(styrene-alt-maleic anhydride)

Anugrah¹,

Patil²,

Li³

et al. 2020

Express Polym. Lett.

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A hydrogel is a cross-linked three-dimensional product of macromolecular hydrophilic networks. Due to their unique properties, hydrogels have been extensively studied for tissue engineering, especially, they have excellent biocompatibility and the capability to be the type of drug delivery system [1, 2]. The high water content provides them with properties similar to natural extracellular matrixes. The risk of the drug denaturation and aggregation due to exposure to an organic solvent can be minimized by hydrogels. The internal network makes hydrogels have solid-like properties. Hydrogel networks may be physical gels or chemical gels. Physical gels form through physical interactions, while chemical gels are held together by covalent bonds. Chemical gel methods for making the internal network have made significant progress so far. Click chemistry, one of the methods, provided hydrogels with moderately high mechanical properties [3-6] and was also useful in biomedical engineering [7-12]. The emerging studies in click chemistry have generated 'metal-free' reactions. One example of interesting metal-free click chemistry is the inverse 248

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“…Generation of Microgel through Microfluidics : PEG thiol‐ene based gel precursor solutions consisted of four‐arm PEG‐norbornene (synthesized from four‐arm PEG‐hydroxyl as previously reported), bifunctional thiol crosslinker, lithium phenyl‐2,4,6‐trimethylbenzoylphosphinate (LAP, synthesized as previously described) photoinitiator, and CGRGDS (prepared via Fmoc solid phase peptide synthesis). The physicochemical properties of the microfluidically generated microgels were tuned by adjusting the gel composition.…”

Section: Methodsmentioning

confidence: 99%

Creating Physicochemical Gradients in Modular Microporous Annealed Particle Hydrogels via a Microfluidic Method

Xin

Dai

Gregory

et al. 2019

Adv Funct Materials

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Microporous annealed particle (MAP) hydrogels are an attractive platform for engineering biomaterials with controlled heterogeneity. Here, a microfluidic method is introduced to create physicochemical gradients within poly(ethylene glycol) based MAP hydrogels. By combining microfluidic mixing and droplet generator modules, microgels with varying properties are produced by adjusting the relative flow rates between two precursor solutions and collected layer-by-layer in a syringe. Subsequently, the microgels are injected out of the syringe and then annealed with thiol-ene click chemistry. Fluorescence intensity measurements of constructs annealed in vitro and after mock implantation into a tissue defect show that a continuous gradient profile is achieved and maintained after injection, indicating utility for in situ hydrogel formation. The effects of physicochemical property gradients on human mesenchymal stem cells (hMSCs) are also studied. Microgel stiffness is studied first, and the hMSCs exhibit increased spreading and proliferation as stiffness increased along the gradient. Microgel degradability is also studied, revealing a critical degradability threshold above which the hMSCs spread robustly and below which they are isolated and exhibit reduced spreading. This method of generating spatial gradients in MAP hydrogels can be further used to gain new insights into cell-material interactions, which can be leveraged for tissue engineering applications.

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Sequential Thiol–Ene and Tetrazine Click Reactions for the Polymerization and Functionalization of Hydrogel Microparticles

Cited by 58 publications

References 55 publications

Inverse‐Electron‐Demand Diels–Alder Reactions: Principles and Applications

Inverse‐Electron‐Demand Diels–Alder Reactions: Principles and Applications

Click-cross-linked, doxorubicin-loaded hydrogels based on poly(styrene-alt-maleic anhydride)

Creating Physicochemical Gradients in Modular Microporous Annealed Particle Hydrogels via a Microfluidic Method

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