Tailoring Gelation Mechanisms for Advanced Hydrogel Applications

Abstract

Hydrogels are one of the most commonly explored classes of biomaterials. Their chemical and structural versatility has enabled their use across a wide range of applications, including tissue engineering, drug delivery, and cell culture. Hydrogels form upon a sol-gel transition, which can be elicited by different triggers designed to enable precise control over hydrogelation kinetics and hydrogel structure. The chosen hydrogelation trigger and chemistry can have a profound effect on the success of the targeted application. In this Progress Report, a critical overview of recent advances in hydrogel design is presented, with a focus on the available strategies used to trigger the formation of hydrogel networks (e.g., temperature, light, ultrasound). These triggers are presented within a new classification system, and their suitability for six key hydrogel-based applications is assessed. This Progress Report is intended to guide trigger selection for new hydrogel applications and inspire the rational design of new hydrogelation trigger mechanisms.

Stimuli‐Responsive Nanocomposite Hydrogels for Biomedical Applications

“…For instance, ultrasound stimuli have been shown to rupture calcium‐loaded liposomes, subsequently triggering ionic crosslinking of alginate‐based hydrogels or activating calcium‐dependent transglutaminases in fibrin‐based matrices. [ 47 ] Stimuli‐transducing nanoparticles allow previously non‐interactable network elements to communicate and transfer the initial triggering signal into a final output, hence expanding the range of stimuli‐responsive hydrogel architectures that can be designed for biomedical applications, as it will be further highlighted in the following sections dedicated to each stimuli input.…”

A library of thermoresponsive PEG‐based methacrylate homopolymers: How do the molar mass and number of ethylene glycol groups affect the cloud point?

“…Thermoresponsive gels (TRGs) are one kind of smart materials which undergo a sol–gel transition when the temperature changes 1–5 . This thermoresponsive property and their formation of a reversible gels makes TRGs promising materials for many biomedical applications, such as tissue engineering, 6–8 protein purification, 9 3‐D bioprinting, 10,11 drug delivery, 8,12 gene therapy, 13 and other industrial applications, for example, sensors, 14,15 and catalysts 16 …”

“…These applications involve mixing the drug or cells with the polymer solution at room temperature in vitro; then upon injection, the polymer forms hydrogel in vivo due to the higher temperature of human body. LCST polymers with slightly lower than 37°C are ideal for these applications, as these ensure that in vivo gelation will take place 6,8 …”

“…LCST polymers with slightly lower than 37 C are ideal for these applications, as these ensure that in vivo gelation will take place. 6,8 Poly (N-isopropyl acrylamide) (PNIPAAm) is one of most commonly studied LCST polymers with LCST at around 32 C. 3,4,17,18 Many PNIPAAm based polymers form gels around body temperature and thus have been researched extensively for biomedical applications such as controlled cell transplantation, drug delivery system. 19,20 However, some properties such as the cytotoxicity of the unreacted NIPAAm monomer and NIPAAm oligomers and the possible absorption of proteins have been found to limit the application of PNIPAAm polymers.…”

“…Thermoresponsive gels (TRGs) are one kind of smart materials which undergo a sol-gel transition when the temperature changes. [1][2][3][4][5] This thermoresponsive property and their formation of a reversible gels makes TRGs promising materials for many biomedical applications, such as tissue engineering, [6][7][8] protein purification, 9 3-D bioprinting, 10,11 drug delivery, 8,12 gene therapy, 13 and other industrial applications, for example, sensors, 14,15 and catalysts. 16 Thermoresponsive polymers are divided into two groups, the lower critical solution temperature (LCST) polymers and the upper critical solution temperature (UCST) polymers, based on how their solubility changes as the temperature changes.…”