Preparation Method of PEG Hydrogel

Polymer hydrogel is a multi-component system composed of a three-dimensional polymer network and solvent water. It is a polymer network that can absorb a large amount of water and cause changes in macroscopic (volume) properties. Its most important property is the swelling property, which directly determines most of the properties of the gel. Intelligent hydrogels refer to those hydrogels that are sensitive to one or more parameters such as temperature, pH value, force, solvent, light intensity, and electric/magnetic field intensity, and their physical and chemical properties will produce reversible changes under their action. Due to the reversible responsiveness of this type of material to external stimuli, it has broad application prospects in high-tech fields such as molecular devices, light-switching materials, mild and efficient separation of biologically active substances, intelligent immobilization of enzymes and cells, and controlled release of drugs.

Fig. 1. PEG hydrogels are formed via thiol-ene reactions (Biomacromolecules. 2023, 24(4): 1617-1626).

PEG Hydrogel Preparation

As a water-soluble polymer, polyethylene glycol (PEG) has non-toxic hydrogels and good biocompatibility, and is widely used in biomedical and pharmaceutical materials. In addition, the end group of the PEG molecular chain is a functional group - hydroxyl group, which can easily undergo chemical reactions to obtain polyethylene glycol functional monomers. In addition, PEG is easy to crystallize, and its molecular weight has a wide application range (from hundreds to tens of thousands). Therefore, using PEG as a matrix to prepare hydrogels has unique advantages.

Free Radical (Co)polymerization

Polyethylene glycol acrylates (Acrylate-PEG) can be used to prepare hydrogels via free radical solution polymerization. The hydrogel's luminescent properties change with temperature. In addition, Professor Chatterji used polyethylene glycol diacrylate aqueous solution to polymerize under the action of initiator ammonium persulfate to obtain a hydrogel. However, it is difficult to obtain a well-structured network structure due to factors such as physical entanglement. Peppas prepared HEMA-co-MAA copolymer hydrogels using PEG600DMA, TEGDMA and PEGMMA polyethylene glycol monomethacrylate as cross-linking agents. It was found that when PEGMMA/TEGDMA (50%) was used as the cross-linking agent, the hydrogel had the highest recognition ability. It is worth mentioning that copolymer hydrogels can be obtained by free radical suspension polymerization of polyethylene glycol dimethacrylate and methacrylic acid. This hydrogel is used in the treatment of diabetes because it can effectively reduce blood sugar concentrations.

Enzyme-catalyzed cross-linking

Hydrogels with polyethylene glycol as the basic skeleton can be prepared by enzymatic cross-linking method. The hydrogel synthesized by the enzyme-catalyzed cross-linking method has the advantages of high efficiency, high selectivity, mild catalytic reaction conditions (generally at normal temperature and normal pressure), and does not require the use of toxic cross-linking agents. Therefore, it has special application value in fields such as drug release.

Click Chemistry

Click chemistry refers to the use of readily available raw materials to achieve the connection of carbon heteroatoms through reliable, efficient and selective chemical reactions. It is a low-cost and rapid method for synthesizing a large number of new compounds. Since click chemistry can achieve "designability" in the synthesis process, it is of great significance in the preparation of polymer hydrogels. Malkou et al. used click chemistry technology to synthesize a new PEG hydrogel with a more regular microstructure. Because the degree of cross-linking of this hydrogel is very large, its performance is greatly improved compared to PEG hydrogels prepared by traditional photochemical cross-linking methods.

Fig. 1. PEG hydrogels formed by thiol-ene photo-click chemistry (Biomaterials. 2011, 32(36): 9685-9695).

Polymer Functional Group Reaction

The end group of the polyethylene glycol molecular chain is an active group - hydroxyl group, so it can chemically react with other multifunctional groups such as isocyanate groups to form hydrogel. In addition, the terminal hydroxyl groups of polyethylene glycol can be easily converted into other active groups, so polyethylene glycol has been widely used in the preparation of hydrogels. Kiuchi reported the preparation of hydrogels from epoxy-terminated polyethylene glycol cross-linked chitosan films. The swelling behavior of cross-linked chitosan strongly depends on the molecular weight and weight fraction of the cross-linking agent, epoxy-terminated polyethylene glycol. Gitsov et al. reported the preparation of hydrogels through the reaction of isocyanate/epoxy-terminated polyethylene glycol and amino-terminated polyphenylene ether dendrimers. The size of the hydrophobic cross-links and hydrophilic network chains in this hydrogel is controllable.

High Energy Radiation Method

High-energy radiation such as gamma rays or electron rays can cross-link water-soluble polymers or unsaturated polymers to form hydrogels. Water can produce hydroxyl radicals after irradiation. These hydroxyl radicals attack polymer chains and produce macromolecular free radicals. The combination of macromolecular free radicals between different chains ultimately leads to the formation of a cross-linked network structure. The reaction conditions for preparing hydrogels using this method are mild (usually at room temperature and physiological pH) and no toxic cross-linking agents are required. But radiation cross-linking may destroy some of the physiological properties of the substance. Ali reported the preparation of PEG/AAc copolymer hydrogels from polyethylene glycol and acrylic acid monomers under γ-ray irradiation. This hydrogel is pH-responsive and can be used as a carrier for drug delivery.

PEG Derivatives for Hydrogels

PEG modifiers used to make hydrogels usually have functional groups such as -OH, -COOH, -SH, -NH₂, -AC, -NHS active esters, acid anhydrides, and esters, which can undergo condensation reactions with other compounds to form cross-linked structures, thereby preparing hydrogels with high water solubility and biocompatibility. BOC Sciences has strong PEG supply capabilities and provides a variety of PEG products with different molecular weights and functions. We have a professional team with extensive experience in PEG synthesis and has established a sound supply chain to ensure reliable and consistent supply of PEG.

References

1. Fan, Y, et al. Placenta Powder-Infused Thiol-Ene PEG Hydrogels as Potential Tissue Engineering Scaffolds. Biomacromolecules. 2023, 24(4): 1617-1626.
2. Lin, C.C. et al. PEG hydrogels formed by thiol-ene photo-click chemistry and their effect on the formation and recovery of insulin-secreting cell spheroids. Biomaterials. 2011, 32(36): 9685-9695.