PEG & Hydrogel Solutions

Owing to their high hydrophilicity, tunable physicochemical properties and antifouling properties, PEG hydrogels are widely used in various biomedical applications, including scaffolds for delivering therapeutic biomolecules and regenerative medicine. The design, fabrication, and characterization of PEG hydrogels depend on the understanding of basic gel dynamics and application purposes. BOC Sciences can provide PEG hydrogel design and development services with different polymerization mechanisms to support the application of these biocompatible hydrogels in regenerative medicine. In addition, design criteria for maintaining the availability and stability of PEG hydrogel biomolecules will be provided.

What is Hydrogel?

Hydrogels are a class of widely studied and applied biomaterials. Hydrogels have been widely studied as cell scaffolds and drug delivery vehicles because their chemical and physical properties are very close to the natural environment of cells. Hydrogels can encapsulate both cells and biomolecules, and many gel systems can closely control the release properties through systematic changes in the physical and chemical structure of the gel. Hydrogels can be formed from synthetic (e.g., poly(ethylene glycol), poly(hydroxyethyl methacrylate)) and naturally occurring polymers (e.g., collagen, hyaluronic acid, heparin). Due to their high water content, hydrogels are able to form in the presence of cells, proteins and DNA. Among them, the versatility and excellent biocompatibility of PEG macromolecular chemistry have facilitated the development of numerous intelligently designed hydrogel systems for regenerative medicine applications.

What is PEG Hydrogel?

PEG hydrogels have been widely used for cell encapsulation and therapeutic protein delivery due to their tissue-like water content, adjustable physicochemical properties and resistance to nonspecific protein adsorption. Through copolymerization with other macromolecules, it is easy to introduce multiple functional groups into PEG hydrogels to inhibit or promote cell survival and function. Chemical or covalent crosslinking is the most commonly used hydrogel crosslinking mechanism, which leads to relatively stable hydrogel structures and tunable physicochemical properties such as permeability, molecular diffusivity, equilibrium water content, elasticity, modulus amount and degradation rate. Among them, chain-growth and step-growth polymerization cross-linking reactions can adjust the mesh size of the hydrogel to control protein release. The mesh size is usually controlled by changing the molecular weight and concentration of monomers. For example, hydrogels with mesh size smaller than the hydrodynamic radius of the encapsulated proteins will result in sustained release of proteins.

Fig. 1. Application of PEG hydrogels in cancer drug delivery (Adv Healthc Mater. 2023, 12(18): e2300105).

The raw materials of PEG hydrogel include polyethylene glycol and cross-linking agent. Among them, PEG is a polymer material with good biocompatibility and can form a gel state in water. Cross-linking agents are substances used to cross-link PEG molecules together to form a three-dimensional network structure. The cross-linking agent can be silica, polyethyleneimine, polyacrylamide, etc. Different cross-linking agents can produce PEG hydrogels with different properties. 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.

PEG Hydrogel Preparation

Currently, three major cross-linking methods have been used to fabricate PEG hydrogels, including irradiation of linear or branched PEG polymers, free radical polymerization (FRP) of PEG acrylates, and specific chemical cross-linking methods. Reactions such as condensation reactions, Michael-type addition reactions, click chemistry, natural chemical ligations, and enzymatic reactions. Of these, the most common method is photopolymerization, which uses light to convert liquid PEG macromer solutions into solid hydrogels at physiological temperatures and pH values. This method facilitates in situ fabrication of hydrogel scaffolds with spatial and temporal control as well as various 3D structures for encapsulating cells and biological agents. PEG acrylates are the main type of macromonomers used for photopolymerization, including PEG diacrylate (PEGDA), PEG dimethacrylate (PEGDMA) and multi-arm PEG acrylate (n-PEG-Acr). Furthermore, PEG hydrogels are not naturally degradable, but degradation can be enhanced by incorporating degradable fragments such as polyesters, polypropylene fumarate (PPF), acetals, and disulfides. Convenient choices for hydrolytically degradable blocks are polyhydroxy acids, including poly(lactic acid) (PEG-PLA), poly(glycolic acid) (PEG-PGA), and polycaprolactone (PEG-PCL). The triblock (ABA) polymers PLA-PEG-PLA and PGA-PEG-PGA have been synthesized by ring-opening polymerization and blocked with acrylate to generate PLA-PEG-PLA diacrylate and PGA-PEG-PGA diacrylate, respectively.

Design criteria for controlled release in PEG-based hydrogels may vary by application due to the variability in the chemical nature and size of the delivered molecules. BOC Sciences can provide controlled delivery screening services of PEG-based hydrogel systems ranging from small molecule drugs to large biomacromolecules such as nucleic acids, peptides and proteins. In addition, we also offer drug availability (correct dosage) screening and biostability testing for PEG hydrogels in order to achieve the desired therapeutic effect in vivo or in vitro. Our PEG hydrogel preparation technologies include:

What Can We Offer?

BOC Sciences' hydrogel preparation capabilities span a variety of stimulus-responsive and non-responsive hydrogels, providing customized solutions for controlled drug delivery, tissue engineering and biomedical applications. Whether enzyme-sensitive, magnetic field-sensitive, reduction-sensitive, photo-sensitive, thermo-sensitive, pH-sensitive, non-responsive or commercial PEG hydrogels, we can customize them in terms of composition, cross-link density and functionalization. In addition, we also support customized development services for PEG hydrogels with antibacterial functions, osteogenic functions or loaded with growth factors.

Enzyme-Sensitive PEG-Hydrogels

Enzyme-sensitive PEG hydrogels are designed to respond to specific enzymes present in biological environments. For example, one of the classic examples of enzymes overproduced in tumor cells is matrix metalloproteinases (MMPs), which are proteases that target and degrade many proteins present in the ECM. The anti-cancer drug doxorubicin (DOX) PEG hydrogel loaded with MMP-degradable peptide can achieve high drug targeted release efficiency. BOC Sciences specializes in preparing enzyme-sensitive hydrogels by incorporating enzyme-cleavable peptide sequences into the PEG network. These peptide sequences can be tailored to be sensitive to various enzymes, such as elastase, lipase, or glycosidase. Upon exposure to target enzymes, the hydrogel degrades or changes in properties, allowing controlled release of encapsulated drugs or bioactive molecules. Our enzyme-sensitive PEG hydrogels enable precise control of drug delivery kinetics and can be customized for different therapeutic applications.

Magnetic Field-Sensitive PEG-Hydrogels

Magnetic hydrogel (MagGel) is a group of composite materials with an inorganic/organic hybrid structure composed of inorganic magnetic nanomaterials (such as Fe₃O₄) and organic hydrogels. MagGel benefits from the properties of magnetic materials and hydrogels, exhibiting excellent biocompatibility and magnetic responsiveness. In order to improve its biocompatibility and circulation stability, polymers such as PEG are often used as its surface coating. Therefore, PEG-MagGel has been used as an environmentally sensitive antitumor drug carrier for magnetic targeted delivery, magnetic responsive release, and magnetic hyperthermia. BOC Sciences' expertise extends to the preparation of magnetic field-sensitive PEG hydrogels that exhibit responsiveness to external magnetic fields, enabling targeted drug delivery, tissue engineering, and soft robotics applications.

Reduction-Sensitive PEG-Hydrogels

The intracellular environment of tumor tissue is more reducing than that of normal tissue. Therefore, reduction-responsive polymers are a favorable platform for drug release specifically at the tumor site. In recent decades, PEG-hydrogels have been considered as reduction-responsive carriers due to their ease of modification through disulfide bonds. Modified disulfide bonds in PEG-hydrogels can be reduced to sulfhydryl groups in the presence of essentially any reducing agent, leading to rapid degradation of the hydrogel and release of the loaded therapeutic agent. Based on this mechanism, BOC Sciences also specifically introduced the preparation of reduction-sensitive hydrogels by incorporating disulfide bonds or other redox-responsive moieties into the PEG matrix. Our PEG-hydrogels are easily modified with disulfide bonds as reduction-reactive cleavable linkers. Furthermore, the positive charge of the entire nanoparticle can be maintained by introducing amine groups, thereby increasing the cellular uptake and intracellular release of antigenic peptides.

Photo-Sensitive PEG-Hydrogels

Photoresponsiveness has been one of the most effective and widely studied exogenous response strategies for on-demand drug delivery. Ultraviolet, visible, and near-infrared (NIR) light are commonly used as exogenous stimuli. Many studies have designed smart PEG hydrogels that can deliver photosensitizers to target sites and enhance therapeutic effects. BOC Sciences' ability to prepare photosensitive PEG hydrogels involves the incorporation of light-responsive molecules or groups that can undergo reversible photoisomerization or photodimerization upon light stimulation. These hydrogels can exhibit changes in swelling behavior, mechanical properties, or drug release kinetics in response to specific wavelengths of light. By controlling light exposure parameters such as intensity, duration, and wavelength, the properties of photosensitive PEG hydrogels can be fine-tuned for on-demand applications in drug delivery, tissue engineering, or biosensing.

Thermo-Sensitive PEG-Hydrogels

Temperature changes were used as exogenous stimuli for thermoresponsive PEG hydrogels to control their drug release behavior. Thermoresponsive PEG hydrogels are a key area of expertise at BOC Sciences, where hydrogel properties are temperature responsive, undergoing reversible transitions between gel and sol states as temperature changes. These hydrogels are often formulated using thermoresponsive polymers such as poly(N-isopropylacrylamide) (PNIPAAm) or polyethylene glycol-b-poly(N-isopropylacrylamide) (PEG-b-PNIPAAm ) copolymer. We can tailor the lower critical solution temperature (LCST) of thermosensitive PEG hydrogels to match specific physiological conditions, enabling applications in injectable drug delivery systems, cell encapsulation, or 3D bioprinting.

pH-Sensitive PEG-Hydrogels

In recent years, PEG has been widely used as an ideal reagent in chemical cross-linking and capping processes to obtain block polymer hydrogels for targeted drug delivery systems by functionalizing pH-responsive groups. The pH-sensitive PEG hydrogels we prepared can respond to pH changes in the acidic or alkaline range. These hydrogels are formulated with pH-responsive polymers or acidic/basic functional groups that can undergo protonation or deprotonation, leading to hydrogel swelling, degradation, or changes in drug release behavior.

Non-Responsive PEG-Hydrogels

In addition to stimulus-responsive hydrogels, BOC Sciences also provides expertise in preparing non-responsive PEG hydrogels that are not sensitive to external stimuli such as enzymes, pH, temperature, or light. Currently, many non-responsive hydrogels are currently used in clinical applications through traditional delivery methods, including oral delivery, transdermal delivery, and local injection. These hydrogels provide a stable and inert matrix for encapsulating drugs, peptides, or proteins without any stimulus-induced changes in properties. Non-responsive PEG hydrogels are ideal for long-term drug release applications, cell culture scaffolds, or as support matrices for the immobilization of bioactive molecules that require a constant environment.

Why Choose BOC Sciences?

BOC Sciences follows strict quality control measures to ensure the purity, consistency and reliability of the prepared PEG hydrogels. We are committed to delivering results on time and at highly competitive prices, helping researchers solve their project needs reliably and efficiently.

Service Workflow for PEG Solutions

Reference

1. Wang, Z. et al. Poly Ethylene Glycol (PEG)-Based Hydrogels for Drug Delivery in Cancer Therapy: A Comprehensive Review. Adv Healthc Mater. 2023, 12(18): e2300105.